Evaluation of Major Cardiovascular Events in Participants With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (ETC-1002) or Placebo (CLEAR Outcomes)

• ClinicalTrials.gov Identifier: NCT02993406
• Recruitment Status: Completed
• First Posted: December 15, 2016
• Results First Posted: January 3, 2024
• Last Update Posted: January 3, 2024
• Sponsor: Esperion Therapeutics, Inc.
• Collaborator: The Cleveland Clinic
• Information provided by (Responsible Party): Esperion Therapeutics, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Cardiovascular Diseases; Statin Adverse Reaction
• Interventions: Drug: Bempedoic acid 180 mg tablet; Drug: Matching placebo tablet
• Enrollment: 13970

Participant Flow

Recruitment Details	This was a randomized, double-blind, placebo-controlled, parallel-group study that assessed the occurrence of major adverse cardiovascular event (MACE) in participants with, or at high risk for, cardiovascular disease (CVD) who were unable to tolerate statin therapy.
Pre-assignment Details	A total of 13970 participants were enrolled from over 1250 sites in 32 countries.

Arm/Group Title	Bempedoic Acid 180 Milligrams (mg)	Placebo Comparator
Arm/Group Description	Participants were administered with Bempedoic acid 180 mg tablet once daily orally.	Participants were administered with matching Placebo tablet once daily orally.
Period Title: Overall Study
Started	6992	6978
Completed	6697	6620
Not Completed	295	358
Reason Not Completed
Withdrawal by Subject	170	196
Physician Decision	3	5
Lost to Follow-up	12	13
Unclassifiable Response	105	139
Administrative decision	1	0
Sponsor decision	4	5

Baseline Characteristics

Arm/Group Title		Bempedoic Acid 180 mg	Placebo Comparator	Total
Arm/Group Description		Participants were administered with Bempedoic acid 180 mg tablet once daily orally.	Participants were administered with matching Placebo tablet once daily orally.	Total of all reporting groups
Overall Number of Baseline Participants		6992	6978	13970
Baseline Analysis Population Description		Intention-to-Treat Population is defined as all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	6992 participants	6978 participants	13970 participants
		65.5 (9.0)	65.5 (8.9)	65.5 (9.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6992 participants	6978 participants	13970 participants
	Female	3361 48.1%	3379 48.4%	6740 48.2%
	Male	3631 51.9%	3599 51.6%	7230 51.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6992 participants	6978 participants	13970 participants
	Hispanic or Latino	1190 17.0%	1143 16.4%	2333 16.7%
	Not Hispanic or Latino	5802 83.0%	5835 83.6%	11637 83.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6992 participants	6978 participants	13970 participants
	American Indian or Alaska Native	240 3.4%	247 3.5%	487 3.5%
	Asian	130 1.9%	136 1.9%	266 1.9%
	Native Hawaiian or Other Pacific Islander	20 0.3%	17 0.2%	37 0.3%
	Black or African American	156 2.2%	172 2.5%	328 2.3%
	White	6397 91.5%	6335 90.8%	12732 91.1%
	More than one race	48 0.7%	70 1.0%	118 0.8%
	Unknown or Not Reported	1 0.0%	1 0.0%	2 0.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With First Occurrence of Four Component Major Adverse Cardiovascular Events (MACE)
Description	The primary efficacy end point was a four-component composite of adjudicated MACE, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, as assessed in a time-to first-event analysis.
Time Frame	Up to 68 months

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Population.

Arm/Group Title	Bempedoic Acid 180 mg	Placebo Comparator
Arm/Group Description:	Participants were administered with Bempedoic acid 180 mg tablet once daily orally.	Participants were administered with matching Placebo tablet once daily orally.
Overall Number of Participants Analyzed	6992	6978
Measure Type: Count of Participants; Unit of Measure: Participants
	819 11.7%	927 13.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempedoic Acid 180 mg, Placebo Comparator
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.79 to 0.96
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Number of Participants With First Occurrence of Three Component MACE
Description	The first key secondary end point was a three-component MACE, defined as death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.
Time Frame	Up to 68 months

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Population.

Arm/Group Title	Bempedoic Acid 180 mg	Placebo Comparator
Arm/Group Description:	Participants were administered with Bempedoic acid 180 mg tablet once daily orally.	Participants were administered with matching Placebo tablet once daily orally.
Overall Number of Participants Analyzed	6992	6978
Measure Type: Count of Participants; Unit of Measure: Participants
	575 8.2%	663 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempedoic Acid 180 mg, Placebo Comparator
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0058
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.76 to 0.96
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Number of Participants With First Occurrence of Myocardial Infarction
Description	Number of participants with time to first occurrence of fatal and non-fatal myocardial infarction are presented.
Time Frame	Up to 68 months

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Population.

Arm/Group Title	Bempedoic Acid 180 mg	Placebo Comparator
Arm/Group Description:	Participants were administered with Bempedoic acid 180 mg tablet once daily orally.	Participants were administered with matching Placebo tablet once daily orally.
Overall Number of Participants Analyzed	6992	6978
Measure Type: Count of Participants; Unit of Measure: Participants
	261 3.7%	334 4.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempedoic Acid 180 mg, Placebo Comparator
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0016
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.66 to 0.91
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Number of Participants With Time to First Occurrence of Coronary Revascularization
Description	Number of participants with time to first occurrence of coronary revascularization are presented.
Time Frame	Up to 68 months

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Population.

Arm/Group Title	Bempedoic Acid 180 mg	Placebo Comparator
Arm/Group Description:	Participants were administered with Bempedoic acid 180 mg tablet once daily orally.	Participants were administered with matching Placebo tablet once daily orally.
Overall Number of Participants Analyzed	6992	6978
Measure Type: Count of Participants; Unit of Measure: Participants
	435 6.2%	529 7.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempedoic Acid 180 mg, Placebo Comparator
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0013
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.72 to 0.92
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Number of Participants With Time to First Occurrence of Stroke
Description	Number of participants with time to first occurrence of fatal and non-fatal stroke.
Time Frame	Up to 68 months

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Population.

Arm/Group Title	Bempedoic Acid 180 mg	Placebo Comparator
Arm/Group Description:	Participants were administered with Bempedoic acid 180 mg tablet once daily orally.	Participants were administered with matching Placebo tablet once daily orally.
Overall Number of Participants Analyzed	6992	6978
Measure Type: Count of Participants; Unit of Measure: Participants
	135 1.9%	158 2.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempedoic Acid 180 mg, Placebo Comparator
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1593
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.07
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Number of Participants With Time to Cardiovascular Death
Description	Number of participants with time to cardiovascular death are presented.
Time Frame	Up to 68 months

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Population.

Arm/Group Title	Bempedoic Acid 180 mg	Placebo Comparator
Arm/Group Description:	Participants were administered with Bempedoic acid 180 mg tablet once daily orally.	Participants were administered with matching Placebo tablet once daily orally.
Overall Number of Participants Analyzed	6992	6978
Measure Type: Count of Participants; Unit of Measure: Participants
	269 3.8%	257 3.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempedoic Acid 180 mg, Placebo Comparator
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6227
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.24
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Number of Participants With Time to All-cause Mortality
Description	All-cause mortality is death due to any cause. Number of participants with time to all-cause mortality are presented.
Time Frame	Up to 68 months

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Population.

Arm/Group Title	Bempedoic Acid 180 mg	Placebo Comparator
Arm/Group Description:	Participants were administered with Bempedoic acid 180 mg tablet once daily orally.	Participants were administered with matching Placebo tablet once daily orally.
Overall Number of Participants Analyzed	6992	6978
Measure Type: Count of Participants; Unit of Measure: Participants
	434 6.2%	420 6.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempedoic Acid 180 mg, Placebo Comparator
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6608
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.18
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Up to 68 months. Serious adverse events (SAEs) and non-SAEs were collected from Safety Population. The Safety Population comprises of all randomized participants who received at least 1 dose of study medication (investigational product). Deaths were endpoints and not reported as SAEs. Negatively adjudicated non- fatal MACE events were reported as SAEs.
Adverse Event Reporting Description	The Safety Analysis Set (SAS) included all participants in the Full Analysis Set who received at least 1 dose of study drug. Participants in the SAS were grouped according to the actual treatment received. Out of 5 participants, 2 randomized to bempedoic acid and 3 to placebo, did not receive any treatment & were not included in the SAS; 11 participants were randomized to placebo but received ≥ to 1 dose of bempedoic acid in error, and were therefore, counted in bempedoic acid group for the SAS.
Arm/Group Title	Bempedoic Acid 180 mg		Placebo Comparator
Arm/Group Description	Participants were administered with Bempedoic acid 180 mg tablet once daily orally.		Participants were administered with matching Placebo tablet once daily orally.
All-Cause Mortality
	Bempedoic Acid 180 mg		Placebo Comparator
	Affected / at Risk (%)		Affected / at Risk (%)
Total	437/7001 (6.24%)		420/6964 (6.03%)
Serious Adverse Events
	Bempedoic Acid 180 mg		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1767/7001 (25.24%)		1733/6964 (24.89%)
Blood and lymphatic system disorders
Anaemia folate deficiency * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Coagulopathy * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Febrile neutropenia * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Haemolytic anaemia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Haemorrhagic disorder * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Hypercoagulation * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Immune thrombocytopenia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Leukopenia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Lymph node pain * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Lymphadenopathy * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Microcytic anaemia * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Normocytic anaemia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Polycythaemia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Splenic infarction * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Thrombocytopenia * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Thrombotic thrombocytopenic purpura * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Anaemia * 1	18/7001 (0.26%)	18	14/6964 (0.20%)	15
Blood loss anaemia * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Iron deficiency anaemia * 1	5/7001 (0.07%)	5	2/6964 (0.03%)	2
Cardiac disorders
Acute coronary syndrome * 1	5/7001 (0.07%)	5	1/6964 (0.01%)	1
Acute left ventricular failure * 1	4/7001 (0.06%)	4	2/6964 (0.03%)	2
Acute myocardial infarction * 1	11/7001 (0.16%)	11	6/6964 (0.09%)	7
Adams-Stokes syndrome * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Angina pectoris * 1	56/7001 (0.80%)	62	82/6964 (1.18%)	84
Angina unstable * 1	56/7001 (0.80%)	58	53/6964 (0.76%)	54
Anginal equivalent * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Aortic valve incompetence * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Aortic valve stenosis * 1	12/7001 (0.17%)	12	6/6964 (0.09%)	6
Arrhythmia * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Arrhythmia supraventricular * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Arteriosclerosis coronary artery * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Arteriospasm coronary * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Atrial fibrillation * 1	81/7001 (1.16%)	107	95/6964 (1.36%)	111
Atrial flutter * 1	14/7001 (0.20%)	17	9/6964 (0.13%)	10
Atrial tachycardia * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Atrioventricular block * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Atrioventricular block complete * 1	7/7001 (0.10%)	8	6/6964 (0.09%)	6
Atrioventricular block second degree * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	5
Bradyarrhythmia * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Bradycardia * 1	9/7001 (0.13%)	10	5/6964 (0.07%)	6
Bundle branch block left * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cardiac arrest * 1	3/7001 (0.04%)	4	7/6964 (0.10%)	7
Cardiac asthma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cardiac failure * 1	35/7001 (0.50%)	43	38/6964 (0.55%)	46
Cardiac failure acute * 1	19/7001 (0.27%)	21	20/6964 (0.29%)	28
Cardiac failure chronic * 1	16/7001 (0.23%)	16	13/6964 (0.19%)	13
Cardiac failure congestive * 1	39/7001 (0.56%)	42	37/6964 (0.53%)	45
Cardiac valve disease * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cardiac ventricular thrombosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cardio-respiratory arrest * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Cardiogenic shock * 1	4/7001 (0.06%)	4	2/6964 (0.03%)	3
Cardiomyopathy * 1	2/7001 (0.03%)	4	2/6964 (0.03%)	2
Cardiopulmonary failure * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cardiorenal syndrome * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Chronic left ventricular failure * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Congestive cardiomyopathy * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Coronary artery disease * 1	25/7001 (0.36%)	26	33/6964 (0.47%)	34
Coronary artery occlusion * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Coronary artery stenosis * 1	4/7001 (0.06%)	4	4/6964 (0.06%)	6
Diastolic dysfunction * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Extrasystoles * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ischaemic cardiomyopathy * 1	2/7001 (0.03%)	2	4/6964 (0.06%)	4
Left ventricular failure * 1	4/7001 (0.06%)	4	7/6964 (0.10%)	10
Microvascular coronary artery disease * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Mitral valve disease * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Mitral valve incompetence * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Myocardial fibrosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Myocardial infarction * 1	28/7001 (0.40%)	28	35/6964 (0.50%)	35
Myocardial ischaemia * 1	7/7001 (0.10%)	7	10/6964 (0.14%)	10
Myocarditis * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Nodal arrhythmia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Nodal rhythm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Palpitations * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Paroxysmal atrioventricular block * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pericardial cyst * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pericardial effusion * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pericardial haemorrhage * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pericarditis * 1	6/7001 (0.09%)	7	2/6964 (0.03%)	2
Pulseless electrical activity * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Right ventricular failure * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Sinus arrest * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Sinus bradycardia * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Sinus node dysfunction * 1	14/7001 (0.20%)	14	10/6964 (0.14%)	10
Stress cardiomyopathy * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	2
Supraventricular extrasystoles * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Supraventricular tachyarrhythmia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Supraventricular tachycardia * 1	4/7001 (0.06%)	4	5/6964 (0.07%)	5
Tachyarrhythmia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Tachycardia * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Trifascicular block * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ventricular arrhythmia * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Ventricular extrasystoles * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Ventricular fibrillation * 1	0/7001 (0.00%)	0	5/6964 (0.07%)	5
Ventricular tachycardia * 1	9/7001 (0.13%)	15	14/6964 (0.20%)	15
Congenital, familial and genetic disorders
Atrial septal defect * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Congenital cystic kidney disease * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Congenital ectopic pancreas * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hereditary neuropathic amyloidosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hypertrophic cardiomyopathy * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Intestinal malrotation * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Trisomy 18 * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Uterine cervix canal atresia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	2
Ear and labyrinth disorders
Acute vestibular syndrome * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Deafness unilateral * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Meniere's disease * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	3
Sudden hearing loss * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Vestibular disorder * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Deafness bilateral * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Tinnitus * 1	2/7001 (0.03%)	3	0/6964 (0.00%)	0
Vertigo * 1	8/7001 (0.11%)	9	8/6964 (0.11%)	8
Vertigo positional * 1	4/7001 (0.06%)	4	4/6964 (0.06%)	4
Endocrine disorders
Goitre * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Hyperparathyroidism * 1	1/7001 (0.01%)	1	3/6964 (0.04%)	3
Hyperparathyroidism primary * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	3
Hyperthyroidism * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hypoparathyroidism * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hypothyroidism * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Thyroid mass * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Toxic nodular goitre * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Eye disorders
Amaurosis fugax * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Amblyopia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Diabetic retinal oedema * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Diabetic retinopathy * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Diplopia * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Macular fibrosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Macular hole * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Macular rupture * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Optic ischaemic neuropathy * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Retinal artery occlusion * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Retinal vascular occlusion * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Retinal vein occlusion * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vision blurred * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Blindness transient * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cataract * 1	12/7001 (0.17%)	13	11/6964 (0.16%)	13
Conjunctival haemorrhage * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Glaucoma * 1	2/7001 (0.03%)	3	2/6964 (0.03%)	2
Retinal detachment * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	2
Gastrointestinal disorders
Abdominal adhesions * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Abdominal hernia * 1	4/7001 (0.06%)	4	0/6964 (0.00%)	0
Abdominal incarcerated hernia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Abdominal pain lower * 1	3/7001 (0.04%)	3	0/6964 (0.00%)	0
Abdominal pain upper * 1	0/7001 (0.00%)	0	7/6964 (0.10%)	7
Abdominal wall haematoma * 1	3/7001 (0.04%)	3	0/6964 (0.00%)	0
Acute abdomen * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Alcoholic pancreatitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	2
Anal fissure * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Anal fistula * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Anal incontinence * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Anal polyp * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Appendicitis noninfective * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Barrett's oesophagus * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Chronic gastritis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Coeliac artery stenosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	3
Colitis * 1	3/7001 (0.04%)	3	5/6964 (0.07%)	5
Colitis ischaemic * 1	3/7001 (0.04%)	3	5/6964 (0.07%)	5
Colitis microscopic * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Colitis ulcerative * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Constipation * 1	4/7001 (0.06%)	4	1/6964 (0.01%)	1
Diaphragmatic hernia * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Diarrhoea * 1	4/7001 (0.06%)	4	6/6964 (0.09%)	6
Dieulafoy's vascular malformation * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Diverticular perforation * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Diverticulum * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Diverticulum intestinal * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Diverticulum intestinal haemorrhagic * 1	1/7001 (0.01%)	1	3/6964 (0.04%)	3
Duodenal stenosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Duodenal ulcer * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Duodenal ulcer haemorrhage * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Duodenitis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Dyspepsia * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	4
Dysphagia * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	3
Enteritis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Enterovesical fistula * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	2
Epiploic appendagitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Erosive duodenitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Faecaloma * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Femoral hernia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Food poisoning * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Gastric haemorrhage * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Gastric ulcer * 1	5/7001 (0.07%)	5	3/6964 (0.04%)	3
Gastric ulcer haemorrhage * 1	5/7001 (0.07%)	5	0/6964 (0.00%)	0
Gastric ulcer perforation * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Gastritis * 1	2/7001 (0.03%)	2	7/6964 (0.10%)	7
Gastritis erosive * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Gastritis haemorrhagic * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Gastrointestinal disorder * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Gastrointestinal haemorrhage * 1	22/7001 (0.31%)	25	21/6964 (0.30%)	24
Gastrointestinal necrosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Gastrointestinal ulcer haemorrhage * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Gastrooesophageal reflux disease * 1	2/7001 (0.03%)	2	6/6964 (0.09%)	6
Haematemesis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Haematochezia * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Haemorrhoidal haemorrhage * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Haemorrhoids * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Hiatus hernia * 1	4/7001 (0.06%)	4	3/6964 (0.04%)	3
Hiatus hernia, obstructive * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ileus * 1	2/7001 (0.03%)	3	1/6964 (0.01%)	1
Impaired gastric emptying * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Incarcerated inguinal hernia * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Incarcerated umbilical hernia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Inguinal hernia * 1	8/7001 (0.11%)	8	8/6964 (0.11%)	8
Inguinal hernia strangulated * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Intestinal angina * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Intestinal haemorrhage * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Intestinal ischaemia * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Intestinal obstruction * 1	5/7001 (0.07%)	5	7/6964 (0.10%)	7
Intestinal polyp * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Intestinal strangulation * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Intra-abdominal fluid collection * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Irritable bowel syndrome * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Jejunal perforation * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Large intestinal obstruction * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Large intestinal stenosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Large intestine perforation * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Large intestine polyp * 1	5/7001 (0.07%)	5	3/6964 (0.04%)	4
Lower gastrointestinal haemorrhage * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Mechanical ileus * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Melaena * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Mesenteric artery embolism * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Mesenteric artery stenosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Nausea * 1	3/7001 (0.04%)	3	0/6964 (0.00%)	0
Obstructive pancreatitis * 1	9/7001 (0.13%)	9	5/6964 (0.07%)	5
Oesophageal food impaction * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Oesophageal motility disorder * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Oesophageal spasm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Oesophageal stenosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Oesophageal ulcer * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Oesophageal varices haemorrhage * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Oesophagitis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Oesophagitis haemorrhagic * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	2
Oesophagitis ulcerative * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pancreatic pseudocyst * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pancreatitis necrotising * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pancreatitis relapsing * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Peptic ulcer * 1	4/7001 (0.06%)	4	0/6964 (0.00%)	0
Pharyngo-oesophageal diverticulum * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pneumatosis intestinalis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Rectal haemorrhage * 1	3/7001 (0.04%)	3	7/6964 (0.10%)	8
Rectal polyp * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Retroperitoneal haematoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Small intestinal haemorrhage * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Small intestinal obstruction * 1	10/7001 (0.14%)	11	11/6964 (0.16%)	13
Spigelian hernia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Stomach granuloma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Subileus * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Umbilical hernia * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Upper gastrointestinal haemorrhage * 1	5/7001 (0.07%)	5	5/6964 (0.07%)	6
Varices oesophageal * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vomiting * 1	5/7001 (0.07%)	5	2/6964 (0.03%)	5
Abdominal pain * 1	13/7001 (0.19%)	13	4/6964 (0.06%)	4
Pancreatitis * 1	11/7001 (0.16%)	17	6/6964 (0.09%)	7
Pancreatitis acute * 1	13/7001 (0.19%)	18	16/6964 (0.23%)	20
General disorders
Chest discomfort * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Complication associated with device * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Complication of device insertion * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Facial pain * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Fatigue * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
General physical health deterioration * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Impaired healing * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Medical device site joint inflammation * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Multiple organ dysfunction syndrome * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Non-cardiac chest pain * 1	50/7001 (0.71%)	55	57/6964 (0.82%)	60
Oedema peripheral * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pain * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Peripheral swelling * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pyrexia * 1	4/7001 (0.06%)	4	1/6964 (0.01%)	1
Strangulated hernia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Swelling * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Swelling face * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Treatment failure * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ulcer haemorrhage * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vascular stent stenosis * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Vessel puncture site haematoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Asthenia * 1	8/7001 (0.11%)	8	8/6964 (0.11%)	8
Chest pain * 1	8/7001 (0.11%)	8	10/6964 (0.14%)	11
Hepatobiliary disorders
Ampulla of Vater stenosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Bile duct stone * 1	6/7001 (0.09%)	6	1/6964 (0.01%)	1
Biliary colic * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Biliary dyskinesia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Biliary obstruction * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Biliary tract disorder * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cholangitis * 1	2/7001 (0.03%)	3	3/6964 (0.04%)	3
Cholangitis acute * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Cholecystitis chronic * 1	4/7001 (0.06%)	4	3/6964 (0.04%)	3
Cholelithiasis * 1	38/7001 (0.54%)	39	15/6964 (0.22%)	15
Cholelithiasis obstructive * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Cholestasis * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Gallbladder disorder * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Gallbladder rupture * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hepatic cirrhosis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Hepatic failure * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hepatic lesion * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hepatic steatosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Jaundice * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Jaundice cholestatic * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Nonalcoholic fatty liver disease * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Post cholecystectomy syndrome * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cholecystitis * 1	18/7001 (0.26%)	21	14/6964 (0.20%)	16
Cholecystitis acute * 1	17/7001 (0.24%)	18	19/6964 (0.27%)	19
Immune system disorders
Anaphylactic reaction * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	5
Anti-neutrophil cytoplasmic antibody positive vasculitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Contrast media allergy * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Drug hypersensitivity * 1	2/7001 (0.03%)	2	5/6964 (0.07%)	5
Heart transplant rejection * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Hypersensitivity * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Sarcoidosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Infections and infestations
COVID-19 * 1	56/7001 (0.80%)	56	75/6964 (1.08%)	76
Abdominal abscess * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Abscess intestinal * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Abscess limb * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Abscess oral * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Acute HIV infection * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Acute sinusitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Anal abscess * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Appendiceal abscess * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Appendicitis * 1	19/7001 (0.27%)	19	8/6964 (0.11%)	8
Appendicitis perforated * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Arthritis bacterial * 1	3/7001 (0.04%)	4	3/6964 (0.04%)	3
Arthritis infective * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Atypical pneumonia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Babesiosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Bacteraemia * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
Bacterial sepsis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Biliary sepsis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Bronchitis * 1	2/7001 (0.03%)	2	6/6964 (0.09%)	6
Bronchitis viral * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Bursitis infective * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
COVID-19 pneumonia * 1	84/7001 (1.20%)	86	90/6964 (1.29%)	90
Campylobacter colitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Campylobacter gastroenteritis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cardiac valve vegetation * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cellulitis * 1	11/7001 (0.16%)	11	21/6964 (0.30%)	21
Cellulitis staphylococcal * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cellulitis streptococcal * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cholecystitis infective * 1	2/7001 (0.03%)	3	2/6964 (0.03%)	2
Chronic sinusitis * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Clostridium colitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Clostridium difficile colitis * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Clostridium difficile infection * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Colonic abscess * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Complicated appendicitis * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Cystitis * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Cystitis klebsiella * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Dengue fever * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Device related bacteraemia * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Device related infection * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Device related sepsis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Diabetic foot infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Diarrhoea infectious * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Diverticulitis * 1	19/7001 (0.27%)	24	27/6964 (0.39%)	35
Diverticulitis intestinal perforated * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
Encephalitis * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Endocarditis * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Endophthalmitis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Enteritis infectious * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Enterobacter bacteraemia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Enterobacter sepsis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Enterococcal sepsis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Epididymitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Epstein-Barr virus infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Erysipelas * 1	4/7001 (0.06%)	5	5/6964 (0.07%)	5
Escherichia bacteraemia * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Escherichia sepsis * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Escherichia urinary tract infection * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Gangrene * 1	7/7001 (0.10%)	8	8/6964 (0.11%)	10
Gastric ulcer helicobacter * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Gastroenteritis * 1	10/7001 (0.14%)	11	7/6964 (0.10%)	7
Gastroenteritis bacterial * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Gastroenteritis salmonella * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Gastroenteritis viral * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Gastroenteritis yersinia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Gastrointestinal infection * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Giardiasis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Groin abscess * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Helicobacter infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hepatitis B * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Herpes zoster * 1	4/7001 (0.06%)	4	2/6964 (0.03%)	2
Herpes zoster oticus * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Infected bite * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Infected skin ulcer * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Infectious pleural effusion * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Infective exacerbation of bronchiectasis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Infective exacerbation of chronic obstructive airways disease * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Infective spondylitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Influenza * 1	8/7001 (0.11%)	8	2/6964 (0.03%)	2
Intervertebral discitis * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Intestinal sepsis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Kidney infection * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Klebsiella sepsis * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Large intestine infection * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Listeriosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Liver abscess * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Localised infection * 1	2/7001 (0.03%)	2	4/6964 (0.06%)	4
Lower respiratory tract infection * 1	4/7001 (0.06%)	4	5/6964 (0.07%)	5
Lung abscess * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Lyme disease * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Medical device site infection * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Meningoencephalitis herpetic * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Myelitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Necrotising fasciitis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Necrotising soft tissue infection * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Ophthalmic herpes zoster * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Orchitis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Osteomyelitis * 1	3/7001 (0.04%)	3	7/6964 (0.10%)	7
Osteomyelitis acute * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Osteomyelitis bacterial * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Otitis externa * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	3
Pancreatic abscess * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Parotitis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pericarditis infective * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Periodontitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Perirectal abscess * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Peritoneal abscess * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Peritonitis * 1	5/7001 (0.07%)	5	0/6964 (0.00%)	0
Peritonsillar abscess * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pilonidal cyst * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pneumonia * 1	84/7001 (1.20%)	93	81/6964 (1.16%)	92
Pneumonia bacterial * 1	5/7001 (0.07%)	5	4/6964 (0.06%)	4
Pneumonia haemophilus * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pneumonia influenzal * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pneumonia legionella * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Pneumonia pseudomonal * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Pneumonia viral * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Post procedural cellulitis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Post procedural infection * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Post procedural sepsis * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Postoperative abscess * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Postoperative wound infection * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Pseudomembranous colitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pulmonary sepsis * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Pulmonary tuberculosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pyelonephritis * 1	7/7001 (0.10%)	7	5/6964 (0.07%)	5
Pyelonephritis acute * 1	3/7001 (0.04%)	3	6/6964 (0.09%)	7
Pyelonephritis chronic * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Rectal abscess * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Respiratory syncytial virus bronchitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Respiratory syncytial virus infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Respiratory tract infection * 1	4/7001 (0.06%)	4	0/6964 (0.00%)	0
Rhinovirus infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
SARS-CoV-2 sepsis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Sepsis * 1	24/7001 (0.34%)	24	22/6964 (0.32%)	24
Septic encephalopathy * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
Septic shock * 1	5/7001 (0.07%)	5	8/6964 (0.11%)	8
Sinusitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Soft tissue infection * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Staphylococcal bacteraemia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Staphylococcal infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Staphylococcal sepsis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Staphylococcal skin infection * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Streptococcal bacteraemia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Suspected COVID-19 * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Syphilis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Systemic infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Tonsillitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Upper respiratory tract infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Urinary tract infection * 1	23/7001 (0.33%)	24	33/6964 (0.47%)	34
Urinary tract infection staphylococcal * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Urosepsis * 1	7/7001 (0.10%)	8	7/6964 (0.10%)	7
Vaginal infection * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Vestibular neuronitis * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Viral infection * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Viral myocarditis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Viral pericarditis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Viral upper respiratory tract infection * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Wound infection * 1	3/7001 (0.04%)	3	0/6964 (0.00%)	0
Wound infection staphylococcal * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Wound sepsis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Injury, poisoning and procedural complications
Accidental overdose * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Acetabulum fracture * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Alcohol poisoning * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Anaemia postoperative * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Anaesthetic complication cardiac * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Animal bite * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ankle fracture * 1	4/7001 (0.06%)	4	3/6964 (0.04%)	3
Arteriovenous graft site stenosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Arthropod bite * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Avulsion fracture * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Brachial plexus injury * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cardiac function disturbance postoperative * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cardiac valve replacement complication * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Carotid artery restenosis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Cartilage injury * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cervical vertebral fracture * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Chest injury * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Clavicle fracture * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Concussion * 1	4/7001 (0.06%)	4	4/6964 (0.06%)	4
Contusion * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Coronary artery restenosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Coronary vascular graft occlusion * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Craniocerebral injury * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
Eschar * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Facial bones fracture * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Fall * 1	6/7001 (0.09%)	6	6/6964 (0.09%)	7
Fibula fracture * 1	1/7001 (0.01%)	1	3/6964 (0.04%)	3
Foot fracture * 1	2/7001 (0.03%)	2	5/6964 (0.07%)	5
Forearm fracture * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	2
Fractured sacrum * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Gun shot wound * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hand fracture * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Head injury * 1	4/7001 (0.06%)	4	5/6964 (0.07%)	5
Heat stroke * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hip fracture * 1	7/7001 (0.10%)	7	9/6964 (0.13%)	9
Incarcerated incisional hernia * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Incisional hernia * 1	4/7001 (0.06%)	4	1/6964 (0.01%)	1
Injury * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Intentional overdose * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Intestinal anastomosis complication * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Joint capsule rupture * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Joint dislocation * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Joint injury * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Limb traumatic amputation * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Lisfranc fracture * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Lower limb fracture * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	2
Lumbar vertebral fracture * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Meniscus injury * 1	5/7001 (0.07%)	5	6/6964 (0.09%)	7
Multiple fractures * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Multiple injuries * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Muscle rupture * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Neck injury * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Overdose * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Patella fracture * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Pelvic fracture * 1	5/7001 (0.07%)	5	3/6964 (0.04%)	3
Periorbital haematoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Peripheral artery restenosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Peripheral nerve injury * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Periprocedural myocardial infarction * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Periprosthetic fracture * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Pharynx radiation injury * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Poisoning deliberate * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Post intensive care syndrome * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Post procedural complication * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Post procedural discomfort * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Post procedural fever * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Post procedural haematoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Post procedural haematuria * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Post procedural haemorrhage * 1	5/7001 (0.07%)	5	5/6964 (0.07%)	5
Post procedural pulmonary embolism * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Postoperative hypertension * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Postoperative ileus * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Postoperative thoracic procedure complication * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Postoperative wound complication * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Procedural complication * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Procedural pain * 1	4/7001 (0.06%)	4	4/6964 (0.06%)	4
Radius fracture * 1	0/7001 (0.00%)	0	4/6964 (0.06%)	4
Rib fracture * 1	7/7001 (0.10%)	7	6/6964 (0.09%)	6
Road traffic accident * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Scapula fracture * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Skin laceration * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Spinal column injury * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Spinal compression fracture * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
Spinal cord injury * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Spinal fracture * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Sternal fracture * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Subdural haematoma * 1	2/7001 (0.03%)	2	8/6964 (0.11%)	9
Subdural haemorrhage * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Suture related complication * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Tendon injury * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Tendon rupture * 1	4/7001 (0.06%)	4	4/6964 (0.06%)	5
Thermal burn * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Thoracic vertebral fracture * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Tibia fracture * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Transplant failure * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Traumatic haematoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Traumatic haemothorax * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Traumatic intracranial haemorrhage * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Traumatic liver injury * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ulna fracture * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Underdose * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Upper limb fracture * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Vascular graft complication * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vascular graft occlusion * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vascular injury * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vascular pseudoaneurysm * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Vascular pseudoaneurysm ruptured * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Wound complication * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Wound dehiscence * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Wound secretion * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Wrist fracture * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
pain * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Femoral neck fracture * 1	7/7001 (0.10%)	8	8/6964 (0.11%)	9
Femur fracture * 1	7/7001 (0.10%)	7	10/6964 (0.14%)	10
Humerus fracture * 1	8/7001 (0.11%)	8	11/6964 (0.16%)	12
Post-traumatic pain * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Investigations
Alanine aminotransferase increased * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Angiocardiogram * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Angiogram * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Aspiration pleural cavity * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Bacterial test * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Biopsy lung * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Blood bicarbonate decreased * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Blood creatinine increased * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Blood glucose decreased * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Blood magnesium decreased * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Blood potassium increased * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Blood pressure increased * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Blood urea increased * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Blood uric acid increased * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cardiac stress test abnormal * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ejection fraction decreased * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Electrocardiogram ST segment depression * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Glomerular filtration rate decreased * 1	3/7001 (0.04%)	4	5/6964 (0.07%)	5
Haemoglobin decreased * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	2
Influenza B virus test positive * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Investigation * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Prostatic specific antigen increased * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Red blood cell sedimentation rate increased * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
SARS-CoV-2 test positive * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Transaminases increased * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Troponin increased * 1	1/7001 (0.01%)	2	2/6964 (0.03%)	2
Weight decreased * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Metabolism and nutrition disorders
Dehydration * 1	7/7001 (0.10%)	7	9/6964 (0.13%)	9
Diabetes mellitus * 1	11/7001 (0.16%)	11	16/6964 (0.23%)	16
Hypoglycaemia * 1	7/7001 (0.10%)	7	7/6964 (0.10%)	7
Decreased appetite * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Diabetes mellitus inadequate control * 1	6/7001 (0.09%)	6	2/6964 (0.03%)	2
Diabetic complication * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Diabetic ketoacidosis * 1	3/7001 (0.04%)	3	0/6964 (0.00%)	0
Diabetic metabolic decompensation * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Electrolyte imbalance * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Failure to thrive * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Fluid overload * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Gout * 1	1/7001 (0.01%)	2	2/6964 (0.03%)	2
Hyperglycaemia * 1	1/7001 (0.01%)	1	4/6964 (0.06%)	4
Hyperglycaemic hyperosmolar nonketotic syndrome * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Hyperkalaemia * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Hypocalcaemia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hypokalaemia * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
Hypomagnesaemia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hyponatraemia * 1	7/7001 (0.10%)	7	9/6964 (0.13%)	10
Hypophagia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hypovolaemia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ketoacidosis * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Lactic acidosis * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Metabolic acidosis * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Obesity * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Type 2 diabetes mellitus * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Musculoskeletal and connective tissue disorders
Arthritis * 1	4/7001 (0.06%)	4	7/6964 (0.10%)	7
Arthropathy * 1	1/7001 (0.01%)	2	1/6964 (0.01%)	1
Back disorder * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Bursitis * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Cartilage hypertrophy * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Cervical spinal stenosis * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Dupuytren's contracture * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Fibromyalgia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Fistula * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Foot deformity * 1	4/7001 (0.06%)	6	1/6964 (0.01%)	1
Fracture pain * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Haemarthrosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Haematoma muscle * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Intervertebral disc degeneration * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Intervertebral disc disorder * 1	4/7001 (0.06%)	4	1/6964 (0.01%)	1
Intervertebral disc protrusion * 1	12/7001 (0.17%)	13	15/6964 (0.22%)	16
Intervertebral disc space narrowing * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Joint stiffness * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Kyphosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Limb discomfort * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Lumbar spinal stenosis * 1	8/7001 (0.11%)	9	9/6964 (0.13%)	11
Metatarsalgia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Muscle haemorrhage * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Muscular weakness * 1	2/7001 (0.03%)	2	4/6964 (0.06%)	5
Musculoskeletal chest pain * 1	10/7001 (0.14%)	12	3/6964 (0.04%)	3
Musculoskeletal pain * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Musculoskeletal stiffness * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Myalgia * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Neck mass * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Neck pain * 1	3/7001 (0.04%)	3	0/6964 (0.00%)	0
Osteoarthritis * 1	71/7001 (1.01%)	81	69/6964 (0.99%)	75
Osteochondrosis * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	3
Osteoporotic fracture * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Pain in extremity * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Pain in jaw * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pathological fracture * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Periarthritis * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
Polyarthritis * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Polymyalgia rheumatica * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Pseudarthrosis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Psoriatic arthropathy * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Rhabdomyolysis * 1	4/7001 (0.06%)	4	1/6964 (0.01%)	1
Rheumatoid arthritis * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
Rotator cuff syndrome * 1	10/7001 (0.14%)	12	3/6964 (0.04%)	3
Spinal osteoarthritis * 1	2/7001 (0.03%)	2	4/6964 (0.06%)	5
Spinal pain * 1	1/7001 (0.01%)	1	4/6964 (0.06%)	4
Spinal stenosis * 1	11/7001 (0.16%)	11	6/6964 (0.09%)	6
Spondylolisthesis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Sympathetic posterior cervical syndrome * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Synovial cyst * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Synovitis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Systemic lupus erythematosus * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Tendonitis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Tenosynovitis stenosans * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Thoracic spinal stenosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Arthralgia * 1	13/7001 (0.19%)	14	12/6964 (0.17%)	13
Back pain * 1	16/7001 (0.23%)	18	11/6964 (0.16%)	11
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acoustic neuroma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Acute myeloid leukaemia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Adenocarcinoma gastric * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Adenocarcinoma of colon * 1	6/7001 (0.09%)	7	4/6964 (0.06%)	4
Adenocarcinoma pancreas * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Adenoma benign * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Adrenal adenoma * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Anal squamous cell carcinoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Appendix cancer * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Astrocytoma * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
B-cell lymphoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Basal cell carcinoma * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Benign breast neoplasm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Benign lung neoplasm * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Benign neoplasm of bladder * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Benign neoplasm of thyroid gland * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Benign ovarian tumour * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Benign renal neoplasm * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Bladder transitional cell carcinoma * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Bone cancer metastatic * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Brain cancer metastatic * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Brain neoplasm * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Brain neoplasm benign * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Brain neoplasm malignant * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Breast cancer female * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Breast cancer recurrent * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Breast cancer stage I * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Breast cancer stage III * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Breast neoplasm * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Bronchial carcinoma * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Bronchial neoplasm * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Carcinoid tumour pulmonary * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Cervix carcinoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cervix carcinoma stage 0 * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Chest wall tumour * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cholangiocarcinoma * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Cholesteatoma * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Chronic lymphocytic leukaemia * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Chronic myeloid leukaemia * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Clear cell renal cell carcinoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Colon adenoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Colon cancer * 1	6/7001 (0.09%)	7	5/6964 (0.07%)	5
Colon cancer metastatic * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Colon neoplasm * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Colorectal adenocarcinoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Colorectal cancer * 1	1/7001 (0.01%)	1	3/6964 (0.04%)	3
Desmoplastic melanoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Diffuse large B-cell lymphoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ductal adenocarcinoma of pancreas * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Enchondromatosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Endometrial adenocarcinoma * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Endometrial cancer * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Epithelioid mesothelioma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Epithelioid sarcoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Follicular thyroid cancer * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Gallbladder adenocarcinoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Gastric cancer * 1	4/7001 (0.06%)	4	1/6964 (0.01%)	1
Gastrointestinal carcinoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Gastrooesophageal cancer * 1	1/7001 (0.01%)	3	0/6964 (0.00%)	0
Glioblastoma * 1	2/7001 (0.03%)	3	1/6964 (0.01%)	1
Glioblastoma multiforme * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Glioma * 1	1/7001 (0.01%)	2	1/6964 (0.01%)	1
Haemangioblastoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hepatic cancer * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hepatic cancer metastatic * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hepatic neoplasm * 1	3/7001 (0.04%)	3	0/6964 (0.00%)	0
Hepatocellular carcinoma * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Hodgkin's disease * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Hormone receptor positive breast cancer * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Intracranial tumour haemorrhage * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Intraductal papilloma of breast * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Intraductal proliferative breast lesion * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Invasive breast carcinoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Invasive ductal breast carcinoma * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	2
Invasive lobular breast carcinoma * 1	3/7001 (0.04%)	3	0/6964 (0.00%)	0
Juvenile melanoma benign * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Laryngeal cancer recurrent * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Laryngeal cancer stage II * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Laryngeal cancer stage III * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Lip and/or oral cavity cancer * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Lip and/or oral cavity cancer stage III * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Lip squamous cell carcinoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Lipoma * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Lung adenocarcinoma * 1	7/7001 (0.10%)	7	3/6964 (0.04%)	3
Lung adenocarcinoma recurrent * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Lung cancer metastatic * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Lung carcinoma cell type unspecified recurrent * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Lung neoplasm * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Lung neoplasm malignant * 1	13/7001 (0.19%)	13	5/6964 (0.07%)	5
Malignant melanoma * 1	5/7001 (0.07%)	5	7/6964 (0.10%)	8
Malignant melanoma in situ * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Malignant mesenteric neoplasm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Malignant neoplasm of ampulla of Vater * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Malignant neoplasm of unknown primary site * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Malignant peritoneal neoplasm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Melanocytic naevus * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Melanoma recurrent * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Meningioma * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Meningioma benign * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Metastases to bone * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Metastases to central nervous system * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Metastases to liver * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	3
Metastases to lung * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Metastases to lymph nodes * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Metastatic carcinoma of the bladder * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Metastatic malignant melanoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Metastatic renal cell carcinoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Metastatic squamous cell carcinoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Metastatic uterine cancer * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Myelodysplastic syndrome * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Neoplasm malignant * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Neoplasm prostate * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Neoplasm skin * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Neuroendocrine carcinoma metastatic * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Neuroendocrine tumour of the lung * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Non-Hodgkin's lymphoma * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Non-small cell lung cancer * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Non-small cell lung cancer stage I * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Oesophageal cancer metastatic * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Oesophageal carcinoma * 1	2/7001 (0.03%)	3	2/6964 (0.03%)	2
Oesophageal neoplasm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Oesophageal squamous cell carcinoma * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Oropharyngeal neoplasm benign * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Ovarian adenoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ovarian cancer * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Ovarian endometrioid carcinoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ovarian neoplasm * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Pancreatic carcinoma * 1	5/7001 (0.07%)	5	3/6964 (0.04%)	3
Pancreatic carcinoma metastatic * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pancreatic neoplasm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Papillary thyroid cancer * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Parathyroid tumour benign * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Penile cancer * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pituitary tumour benign * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Plasma cell myeloma * 1	2/7001 (0.03%)	3	0/6964 (0.00%)	0
Prostate cancer metastatic * 1	1/7001 (0.01%)	1	6/6964 (0.09%)	6
Prostatic adenoma * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Rectal adenocarcinoma * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Rectal cancer * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	2
Rectal cancer stage II * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Rectal neoplasm * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Renal cancer * 1	4/7001 (0.06%)	4	3/6964 (0.04%)	3
Renal cancer metastatic * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Renal cell carcinoma * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Renal neoplasm * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Salivary gland cancer * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Schwannoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Seborrhoeic keratosis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Skin cancer * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Small cell lung cancer * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	2
Small cell lung cancer metastatic * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Small intestine carcinoma * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Squamous cell carcinoma of lung * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Squamous cell carcinoma of skin * 1	1/7001 (0.01%)	1	3/6964 (0.04%)	3
Squamous cell carcinoma of the oral cavity * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Thyroid adenoma * 1	0/7001 (0.00%)	0	3/6964 (0.04%)	3
Thyroid cancer stage III * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Tongue cancer metastatic * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Tongue neoplasm malignant stage unspecified * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Tonsil cancer * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Tonsil cancer metastatic * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Transitional cell cancer of the renal pelvis and ureter * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Transitional cell carcinoma * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Ureteral neoplasm * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Uterine cancer * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Uterine leiomyoma * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Bladder cancer * 1	9/7001 (0.13%)	10	7/6964 (0.10%)	7
Breast cancer * 1	14/7001 (0.20%)	14	23/6964 (0.33%)	24
Prostate cancer * 1	19/7001 (0.27%)	19	21/6964 (0.30%)	21
Nervous system disorders
Carotid artery stenosis * 1	23/7001 (0.33%)	24	16/6964 (0.23%)	18
Syncope * 1	23/7001 (0.33%)	25	27/6964 (0.39%)	28
Altered state of consciousness * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Amnesia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Aphasia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Axonal neuropathy * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Balance disorder * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Basal ganglia haemorrhage * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Basilar artery aneurysm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Basilar artery occlusion * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Brain injury * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Brain oedema * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Carotid arteriosclerosis * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Carotid artery aneurysm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Carotid artery disease * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Carotid artery occlusion * 1	1/7001 (0.01%)	1	3/6964 (0.04%)	3
Carpal tunnel syndrome * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Cerebellar haemorrhage * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cerebellar syndrome * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cerebral atrophy * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cerebral haematoma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cerebral haemorrhage * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	2
Cerebral infarction * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Cerebral ischaemia * 1	5/7001 (0.07%)	6	0/6964 (0.00%)	0
Cerebrovascular accident * 1	21/7001 (0.30%)	21	25/6964 (0.36%)	25
Cerebrovascular insufficiency * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Cervical radiculopathy * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Cognitive disorder * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Coma * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Delayed ischaemic neurological deficit * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Dementia * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Dementia Alzheimer's type * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Diabetic neuropathy * 1	4/7001 (0.06%)	4	0/6964 (0.00%)	0
Dizziness * 1	7/7001 (0.10%)	8	6/6964 (0.09%)	6
Dysarthria * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Dystonia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Encephalitis toxic * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Encephalopathy * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Epilepsy * 1	5/7001 (0.07%)	8	2/6964 (0.03%)	2
Facial paralysis * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Frontotemporal dementia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Guillain-Barre syndrome * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Haemorrhagic stroke * 1	4/7001 (0.06%)	4	5/6964 (0.07%)	5
Headache * 1	5/7001 (0.07%)	5	2/6964 (0.03%)	2
Hemiparesis * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Hydrocephalus * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hyperglycaemic unconsciousness * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hypertensive encephalopathy * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Hypoaesthesia * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Intensive care unit acquired weakness * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Intercostal neuralgia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Intracranial aneurysm * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Intraventricular haemorrhage * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ischaemic cerebral infarction * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ischaemic stroke * 1	10/7001 (0.14%)	10	14/6964 (0.20%)	14
Lacunar infarction * 1	4/7001 (0.06%)	4	1/6964 (0.01%)	1
Lethargy * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Leukoencephalopathy * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Loss of consciousness * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Lumbar radiculopathy * 1	2/7001 (0.03%)	2	4/6964 (0.06%)	4
Lumbosacral radiculopathy * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Metabolic encephalopathy * 1	5/7001 (0.07%)	5	6/6964 (0.09%)	6
Migraine * 1	3/7001 (0.04%)	7	2/6964 (0.03%)	2
Monoplegia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Myasthenia gravis * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Myelopathy * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Myoclonus * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Nerve compression * 1	1/7001 (0.01%)	1	3/6964 (0.04%)	3
Neuralgia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Neuropathy peripheral * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Normal pressure hydrocephalus * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Optic neuritis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Paralysis recurrent laryngeal nerve * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Paraparesis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Paresis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Parkinson's disease * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Partial seizures * 1	0/7001 (0.00%)	0	4/6964 (0.06%)	4
Peripheral nerve lesion * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Polyneuropathy * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Presyncope * 1	7/7001 (0.10%)	7	6/6964 (0.09%)	6
Radicular pain * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Radiculopathy * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Sciatica * 1	1/7001 (0.01%)	1	3/6964 (0.04%)	3
Seizure * 1	5/7001 (0.07%)	5	5/6964 (0.07%)	6
Spinal claudication * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Spinal cord compression * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Spinal cord herniation * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Status epilepticus * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Subarachnoid haemorrhage * 1	4/7001 (0.06%)	4	0/6964 (0.00%)	0
Tension headache * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Thoracic outlet syndrome * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Toxic encephalopathy * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Transient global amnesia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Transient ischaemic attack * 1	41/7001 (0.59%)	43	36/6964 (0.52%)	36
Unresponsive to stimuli * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vascular dementia * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Vascular encephalopathy * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Vasogenic cerebral oedema * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vertebral artery dissection * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Vertebrobasilar insufficiency * 1	3/7001 (0.04%)	3	0/6964 (0.00%)	0
Vertebrobasilar stroke * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vertigo CNS origin * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Vocal cord paralysis * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Pregnancy, puerperium and perinatal conditions
Stillbirth * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Product Issues
Device breakage * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Device dislocation * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Device end of service * 1	0/7001 (0.00%)	0	4/6964 (0.06%)	4
Device failure * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Device lead damage * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Device loosening * 1	1/7001 (0.01%)	3	0/6964 (0.00%)	0
Device malfunction * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Device occlusion * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Psychiatric disorders
Acute psychosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Alcohol use disorder * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Alcohol withdrawal syndrome * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Alcoholism * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Confusional state * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Delirium * 1	1/7001 (0.01%)	1	6/6964 (0.09%)	7
Delusional disorder, unspecified type * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Depression suicidal * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Drug abuse * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	4
Emotional distress * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hallucination, auditory * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Insomnia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Mood disorder due to a general medical condition * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Panic attack * 1	1/7001 (0.01%)	1	3/6964 (0.04%)	3
Post-traumatic stress disorder * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	2
Sleep disorder * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Somatic symptom disorder * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Stress * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Suicidal ideation * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Suicide attempt * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Anxiety * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Depression * 1	2/7001 (0.03%)	2	8/6964 (0.11%)	10
Major depression * 1	2/7001 (0.03%)	4	1/6964 (0.01%)	1
Mental status changes * 1	3/7001 (0.04%)	3	5/6964 (0.07%)	5
Renal and urinary disorders
Bladder diverticulum * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Bladder prolapse * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Bladder tamponade * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Calculus bladder * 1	0/7001 (0.00%)	0	4/6964 (0.06%)	4
Calculus urinary * 1	5/7001 (0.07%)	5	2/6964 (0.03%)	2
Chronic kidney disease * 1	7/7001 (0.10%)	7	3/6964 (0.04%)	3
Cystitis haemorrhagic * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Diabetic nephropathy * 1	2/7001 (0.03%)	3	0/6964 (0.00%)	0
Dysuria * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
End stage renal disease * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Hydronephrosis * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Hypertonic bladder * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Nephrolithiasis * 1	17/7001 (0.24%)	26	15/6964 (0.22%)	17
Nephropathy * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Nephropathy toxic * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Nephrosclerosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pelvi-ureteric obstruction * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Renal artery arteriosclerosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Renal artery stenosis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Renal colic * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Renal cyst * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Renal cyst ruptured * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Renal disorder * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Renal failure * 1	7/7001 (0.10%)	7	6/6964 (0.09%)	7
Renal hypertension * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Renal impairment * 1	4/7001 (0.06%)	4	2/6964 (0.03%)	2
Renal infarct * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Renal injury * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Renal mass * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Renal tubular necrosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Tubulointerstitial nephritis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Urate nephropathy * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ureterolithiasis * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	2
Urethral meatus stenosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Urethral stenosis * 1	2/7001 (0.03%)	6	1/6964 (0.01%)	1
Urge incontinence * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Urinary bladder haemorrhage * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Urinary bladder polyp * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	2
Urinary incontinence * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Urinary retention * 1	7/7001 (0.10%)	7	5/6964 (0.07%)	5
Urinary tract obstruction * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Acute kidney injury * 1	35/7001 (0.50%)	37	29/6964 (0.42%)	32
Haematuria * 1	8/7001 (0.11%)	8	4/6964 (0.06%)	5
Reproductive system and breast disorders
Benign prostatic hyperplasia * 1	19/7001 (0.27%)	21	15/6964 (0.22%)	15
Uterine polyp * 1	4/7001 (0.06%)	4	0/6964 (0.00%)	0
Acquired hydrocele * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	3
Breast discomfort * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Breast enlargement * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Breast mass * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cervical dysplasia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Cystocele * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Endometrial hyperplasia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Epididymal cyst * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Ovarian cyst * 1	1/7001 (0.01%)	1	5/6964 (0.07%)	5
Pelvic haemorrhage * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Peyronie's disease * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Postmenopausal haemorrhage * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Prostatism * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Prostatitis * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Prostatomegaly * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Rectocele * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Uterine haemorrhage * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Uterine prolapse * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Uterovaginal prolapse * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Vaginal prolapse * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Vulvovaginal adhesion * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease * 1	24/7001 (0.34%)	33	27/6964 (0.39%)	33
Pulmonary embolism * 1	22/7001 (0.31%)	24	29/6964 (0.42%)	30
Acquired diaphragmatic eventration * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Acute pulmonary oedema * 1	3/7001 (0.04%)	3	1/6964 (0.01%)	1
Acute respiratory distress syndrome * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Acute respiratory failure * 1	18/7001 (0.26%)	18	29/6964 (0.42%)	32
Aphonia * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Asthma * 1	9/7001 (0.13%)	9	11/6964 (0.16%)	13
Asthma late onset * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Asthma-chronic obstructive pulmonary disease overlap syndrome * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Atelectasis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Bronchial hyperreactivity * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Bronchiectasis * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Bronchitis chronic * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Bronchospasm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Combined pulmonary fibrosis and emphysema * 1	1/7001 (0.01%)	2	0/6964 (0.00%)	0
Cough * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Diaphragmatic paralysis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Dyspnoea * 1	11/7001 (0.16%)	11	14/6964 (0.20%)	15
Dyspnoea exertional * 1	2/7001 (0.03%)	2	4/6964 (0.06%)	4
Emphysema * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Epistaxis * 1	4/7001 (0.06%)	4	3/6964 (0.04%)	4
Haemoptysis * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Hypersensitivity pneumonitis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	2
Hypoxia * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Idiopathic pulmonary fibrosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Interstitial lung disease * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Laryngospasm * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Lung infiltration * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Nasal septum deviation * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Nasal septum haematoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Nasal turbinate abnormality * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pharyngeal cyst * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pharyngeal haemorrhage * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pleural effusion * 1	7/7001 (0.10%)	9	6/6964 (0.09%)	6
Pneumonia aspiration * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Pneumothorax * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Pneumothorax spontaneous * 1	1/7001 (0.01%)	2	2/6964 (0.03%)	2
Pulmonary arterial hypertension * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pulmonary congestion * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pulmonary fibrosis * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Pulmonary hypertension * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pulmonary mass * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Pulmonary microemboli * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Pulmonary oedema * 1	6/7001 (0.09%)	6	3/6964 (0.04%)	3
Respiratory acidosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Respiratory distress * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Respiratory failure * 1	8/7001 (0.11%)	8	11/6964 (0.16%)	12
Sleep apnoea syndrome * 1	3/7001 (0.04%)	3	3/6964 (0.04%)	3
Throat tightness * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Tracheobronchial dyskinesia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vocal cord leukoplakia * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Skin and subcutaneous tissue disorders
Diabetic foot * 1	6/7001 (0.09%)	6	5/6964 (0.07%)	6
Skin ulcer * 1	5/7001 (0.07%)	5	4/6964 (0.06%)	6
Adiposis dolorosa * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Angioedema * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Dermatitis allergic * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Eczema * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hyperhidrosis * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Nail bed inflammation * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Peau d'orange * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Psoriasis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Rash * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Rash pruritic * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Skin lesion * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Skin ulcer haemorrhage * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Stasis dermatitis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Subcutaneous emphysema * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Urticaria * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Social circumstances
Amputee * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Cardiac assistance device user * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Cardiac valve prosthesis user * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vascular disorders
Accelerated hypertension * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Aortic aneurysm * 1	13/7001 (0.19%)	13	9/6964 (0.13%)	9
Aortic aneurysm rupture * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Aortic dissection * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	3
Aortic intramural haematoma * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Aortic occlusion * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	2
Aortic stenosis * 1	13/7001 (0.19%)	14	5/6964 (0.07%)	5
Aortic thrombosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Arterial thrombosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Arteriosclerosis * 1	2/7001 (0.03%)	2	3/6964 (0.04%)	3
Arteriovenous fistula * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Brachiocephalic artery stenosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Circulatory collapse * 1	1/7001 (0.01%)	1	2/6964 (0.03%)	2
Deep vein thrombosis * 1	5/7001 (0.07%)	5	19/6964 (0.27%)	20
Diabetic vascular disorder * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Dry gangrene * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Embolism arterial * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Essential hypertension * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Extremity necrosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Giant cell arteritis * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Haematoma * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	2
Hypertension * 1	29/7001 (0.41%)	29	26/6964 (0.37%)	30
Hypertensive crisis * 1	16/7001 (0.23%)	16	9/6964 (0.13%)	12
Hypertensive emergency * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Hypertensive urgency * 1	3/7001 (0.04%)	3	6/6964 (0.09%)	6
Hypotension * 1	5/7001 (0.07%)	6	11/6964 (0.16%)	11
Hypovolaemic shock * 1	4/7001 (0.06%)	4	1/6964 (0.01%)	1
Iliac artery occlusion * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Iliac artery stenosis * 1	4/7001 (0.06%)	4	4/6964 (0.06%)	4
Intermittent claudication * 1	2/7001 (0.03%)	5	3/6964 (0.04%)	3
Internal haemorrhage * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Jugular vein thrombosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Labile hypertension * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Leriche syndrome * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Orthostatic hypotension * 1	3/7001 (0.04%)	3	2/6964 (0.03%)	3
Penetrating atherosclerotic ulcer * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Peripheral arterial occlusive disease * 1	30/7001 (0.43%)	43	25/6964 (0.36%)	40
Peripheral artery aneurysm * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Peripheral artery occlusion * 1	3/7001 (0.04%)	4	5/6964 (0.07%)	6
Peripheral artery stenosis * 1	3/7001 (0.04%)	3	4/6964 (0.06%)	4
Peripheral artery thrombosis * 1	2/7001 (0.03%)	2	1/6964 (0.01%)	1
Peripheral embolism * 1	1/7001 (0.01%)	1	1/6964 (0.01%)	1
Peripheral ischaemia * 1	5/7001 (0.07%)	5	7/6964 (0.10%)	7
Peripheral vascular disorder * 1	3/7001 (0.04%)	4	9/6964 (0.13%)	11
Poor peripheral circulation * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Raynaud's phenomenon * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Renovascular hypertension * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
Shock * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Shock haemorrhagic * 1	2/7001 (0.03%)	2	0/6964 (0.00%)	0
Subclavian artery stenosis * 1	0/7001 (0.00%)	0	2/6964 (0.03%)	2
Subclavian vein thrombosis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Thrombophlebitis * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Thrombophlebitis superficial * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Thrombosis * 1	2/7001 (0.03%)	2	2/6964 (0.03%)	2
Varicose vein * 1	2/7001 (0.03%)	2	4/6964 (0.06%)	4
Varicose vein ruptured * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Vasospasm * 1	1/7001 (0.01%)	1	0/6964 (0.00%)	0
Venous thrombosis * 1	0/7001 (0.00%)	0	1/6964 (0.01%)	1
1 Term from vocabulary, MedDRA (23.1); * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bempedoic Acid 180 mg		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5805/7001 (82.92%)		5490/6964 (78.83%)
Infections and infestations
COVID-19 * 1	731/7001 (10.44%)	756	801/6964 (11.50%)	826
Urinary tract infection * 1	539/7001 (7.70%)	802	515/6964 (7.40%)	784
Nasopharyngitis * 1	351/7001 (5.01%)	424	389/6964 (5.59%)	462
Investigations
Blood uric acid increased * 1	393/7001 (5.61%)	439	186/6964 (2.67%)	201
Metabolism and nutrition disorders
Hyperuricaemia * 1	763/7001 (10.90%)	868	393/6964 (5.64%)	435
Diabetes mellitus * 1	458/7001 (6.54%)	509	435/6964 (6.25%)	475
Musculoskeletal and connective tissue disorders
Arthralgia * 1	548/7001 (7.83%)	675	554/6964 (7.96%)	722
Back pain * 1	404/7001 (5.77%)	458	450/6964 (6.46%)	511
Myalgia * 1	392/7001 (5.60%)	511	470/6964 (6.75%)	599
Nervous system disorders
Headache * 1	479/7001 (6.84%)	572	493/6964 (7.08%)	574
Vascular disorders
Hypertension * 1	747/7001 (10.67%)	907	804/6964 (11.55%)	978
1 Term from vocabulary, MedDRA (23.1); * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

If the Principal Investigator plans to publish information from the study, a copy of the manuscript should be provided to the Sponsor for review before submission for publication or presentation. The Sponsor may request that that publication be withheld.

Results Point of Contact

• Name/Title: Medical Director
• Organization: Esperion Therapeutics, Inc.
• Phone: 1-833-377-7633
• EMail: medinfo@esperion.com

Publications:

Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038/ncomms13457.

Bilen O, Ballantyne CM. Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep. 2016 Oct;18(10):61. doi: 10.1007/s11883-016-0611-4.

Thompson PD, MacDougall DE, Newton RS, Margulies JR, Hanselman JC, Orloff DG, McKenney JM, Ballantyne CM. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol. 2016 May-Jun;10(3):556-67. doi: 10.1016/j.jacl.2015.12.025. Epub 2016 Jan 6.

Thompson PD, Rubino J, Janik MJ, MacDougall DE, McBride SJ, Margulies JR, Newton RS. Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance. J Clin Lipidol. 2015 May-Jun;9(3):295-304. doi: 10.1016/j.jacl.2015.03.003. Epub 2015 Mar 19.

Nicholls S, Lincoff AM, Bays HE, Cho L, Grobbee DE, Kastelein JJ, Libby P, Moriarty PM, Plutzky J, Ray KK, Thompson PD, Sasiela W, Mason D, McCluskey J, Davey D, Wolski K, Nissen SE. Rationale and design of the CLEAR-outcomes trial: Evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance. Am Heart J. 2021 May;235:104-112. doi: 10.1016/j.ahj.2020.10.060. Epub 2020 Oct 24.

Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, Thompson PD, Libby P, Cho L, Plutzky J, Bays HE, Moriarty PM, Menon V, Grobbee DE, Louie MJ, Chen CF, Li N, Bloedon L, Robinson P, Horner M, Sasiela WJ, McCluskey J, Davey D, Fajardo-Campos P, Petrovic P, Fedacko J, Zmuda W, Lukyanov Y, Nicholls SJ; CLEAR Outcomes Investigators. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023 Apr 13;388(15):1353-1364. doi: 10.1056/NEJMoa2215024. Epub 2023 Mar 4.

Nissen SE, Menon V, Nicholls SJ, Brennan D, Laffin L, Ridker P, Ray KK, Mason D, Kastelein JJP, Cho L, Libby P, Li N, Foody J, Louie MJ, Lincoff AM. Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients. JAMA. 2023 Jul 11;330(2):131-140. doi: 10.1001/jama.2023.9696.

• Responsible Party: Esperion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02993406
• Other Study ID Numbers: 1002-043
• First Submitted: December 9, 2016
• First Posted: December 15, 2016
• Results First Submitted: October 25, 2023
• Results First Posted: January 3, 2024
• Last Update Posted: January 3, 2024