History of Changes for Study: NCT02651428

Study Assessing Safety & Effectiveness of a Catheter Lock Solution in Dialysis Patients to Prevent Bloodstream Infection

A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.

Study Record Versions

Version	Submitted Date	Changes
1	January 7, 2016	None (earliest Version on record)
2	January 23, 2016	Contacts/Locations and Study Status
3	February 1, 2016	Contacts/Locations and Study Status
4	February 7, 2016	Study Status and Contacts/Locations
5	September 3, 2019	Recruitment Status, Study Status, Contacts/Locations and Study Design
6	August 4, 2020	Study Status and Study Design
7	August 6, 2020	Arms and Interventions and Study Status
	Results Submission Events
April 28, 2021		Returned after QC review: May 18, 2021
8	August 5, 2021	Study Status, Outcome Measures, More Information, Document Section, Adverse Events, Baseline Characteristics and Participant Flow

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	LOCK-IT-100
Brief Title:	Study Assessing Safety & Effectiveness of a Catheter Lock Solution in Dialysis Patients to Prevent Bloodstream Infection
Official Title:	Phase 3 Prospective, Multicenter, Double-blind, Randomized, Active Control Study to Demonstrate Safety & Effectiveness of Neutrolin in Preventing Catheter-related Bloodstream Infection in Subjects on Hemodialysis for End Stage Renal Disease
Secondary IDs:

Study Status


Record Verification:	August 2021
Overall Status:	Completed
Study Start:	December 2015
Primary Completion:	October 2018 [Actual]
Study Completion:	October 2018 [Actual]

First Submitted:	January 7, 2016
First Submitted that Met QC Criteria:	January 7, 2016
First Posted:	January 11, 2016 [Estimate]

Results First Submitted:	April 28, 2021
Results First Submitted that Met QC Criteria:	August 5, 2021
Results First Posted:	August 31, 2021 [Actual]

Certification/Extension First Submitted:	August 4, 2020
Certification/Extension First Submitted that Met QC Criteria:	August 4, 2020
Certification/Extension First Posted:	August 7, 2020 [Actual]

Last Update Submitted that Met QC Criteria:	August 5, 2021
Last Update Posted:	August 31, 2021 [Actual]

Sponsor/Collaborators


Sponsor:	CorMedix
Responsible Party:	Sponsor
Collaborators:	PPD JMI Laboratories Spectra Clinical Research Davita Clinical Research Frenova Renal Research

Oversight


U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:	Yes

Study Description

Brief Summary:

The purpose of this study is determine safety and effectiveness of Neutrolin, a catheter lock solution, for prevention of central venous catheter associated bloodstream infection in hemodialysis patients.

Detailed Description:

The objective of this study is to demonstrate the efficacy and safety of Neutrolin® as a catheter lock solution (CLS) on prevention of catheter-related bloodstream infection (CRBSI), and the incidence of treatment-emergent adverse events in subjects receiving hemodialysis (HD) for the treatment of End Stage Renal Disease (ESRD) when compared with heparin 4,000 USP Units/4mL (1,000 USP Units/mL).

This is a randomized, double-blind, active control, parallel-arm, multicenter study. Six hundred and thirty two subjects will be randomized in a 1:1 ratio to receive either Neutrolin® or the active control heparin (Heparin sodium USP 1,000 units/mL, Benzyl alcohol 9.45 mg/mL and Sodium chloride 9.0 mg/mL) as a CLS.

Approximately 632 randomized subjects are planned for this trial. In this study, one-half of the subjects (316 subjects) will receive Neutrolin as a study drug and the other half will receive heparin 4,000 USP Units/4mL (1,000 USP Units/mL) with benzyl alcohol preservative as a comparator. Subjects will be assigned in a 1:1 ratio using permuted blocks without additional stratification for both groups.

The primary objective of this study is to demonstrate the effectiveness of Neutrolin® as a CLS in ESRD subjects undergoing HD treatment using a permanent, cuffed, tunneled silicone or polyurethane HD catheter. The study will evaluate whether Neutrolin® is superior to the active control heparin by documenting the time to CRBSI and consequently delaying the time until the occurrence of CRBSI.

Conditions


Conditions:	Kidney Failure, Chronic Catheter-Related Infections
Keywords:	Kidney Failure, Chronic Catheter-Related Infections Central Venous Catheter

Study Design


Study Type:	Interventional
Primary Purpose:	Prevention
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Triple (Participant, Care Provider, Investigator)
Allocation:	Randomized
Enrollment:	806 [Actual]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Neutrolin arm Neutrolin: Neutrolin will be added to the central venous catheter after dialysis as a lock solution	Drug: Neutrolin Neutrolin® will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session Other Names: 1.35% taurolidine, 3.5% citrate, heparin 1,000 USP Units/mL
Active Comparator: Heparin arm Heparin: Heparin will be added to the central venous catheter after dialysis as a lock solution	Drug: Heparin Heparin will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session Other Names: Heparin Sodium

Outcome Measures

[See Results Section.]


Primary Outcome Measures:
1.	Presence of a CAC-Adjudicated Catheter-Related Bloodstream Infection (CRBSI) in Subjects Receiving Hemodialysis for the Treatment of End Stage Renal Disease (ESRD): Final Analysis [ Time Frame: The event time was the number of days from randomization until the occurrence of a CAC-Adjudicated CRBSI or until the subject was censored. The mean participant duration of exposure to study drug was 174 days (range 4-884 days). ] CRBSI was defined as the same organism grown from at least one positive blood culture from a peripheral site or bloodline sample, or either the arterial or venous catheter hub. The final assessment of CRBSI was determined by a Clinical Adjudication Committee (CAC) who used both clinical documentation and blood culture results in their assessment.
Secondary Outcome Measures:
1.	Participants With a Study Catheter Removal for Any Reason [ Time Frame: The event time was the number of days from randomization until catheter removal for any reason or until the subject was censored. The mean participant duration of exposure to study drug was 174 days (range 4-884 days). ] Analysis of all catheter removals during the study or until the catheter was removed

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Subject has ESRD and undergoes chronic HD at least two times per week Subject has a HD catheter that has demonstrated the ability to achieve a minimum blood flow of at least 250 mL/min for at least two consecutive dialysis sessions blood flow to enable successful HD The HD catheter is implanted with the tip in a jugular or subclavian vein The subject is not expected to expire within 180 days The subject is likely to require the use of a CVC for at least 90 days The subject (or the legal guardian) understands the nature of the study and provides written informed consent prior to the study enrollment The subject is willing to comply with specified follow-up evaluations and prescribed dialysis therapy and If female and of childbearing potential, the subject must have a negative pregnancy test at the screening visit (i.e., subject is not pregnant); not be lactating; and use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or hormonal contraceptive (oral, implant, ring, patch) for the duration of the study. (NOTE: The subject must have used the chosen method of birth control for at least 1 month/cycle prior to enrollment into the study). Exclusion Criteria: Subjects who received antibiotics within the last 14 days Visible evidence of compromised skin integrity is present at the catheter exit site or evidence of a catheter exit site infection Subject has received any thrombolytic treatment (i.e., tPA) in their current catheter within 30 days of randomization Fill volume of HD catheter is unknown or cannot be determined Subjects using any type of antimicrobial-coated or heparin-coated catheter Documented chronic bleeding diathesis, active or recurrent bleeding within 1 month prior to randomization Documented history of an atrial thrombus or known hypercoagulable state Subjects with open, non-healing skin ulcers Current requirement for systemic immunosuppression that would increase risk of infection Active malignancy requiring or anticipated to require chemotherapy likely to cause leukopenia and/or immunosuppression Known allergy or absolute contraindication to citrate, taurolidine or heparin or a history of heparin-induced thrombocytopenia Unstable malignancy Cirrhosis with encephalopathy Subject is currently taking another medication with known systemic drug interaction with citrate, taurolidine, or heparin Subject is currently enrolled in another investigational device and/or drug trial or has participated in another investigational device and/or drug trial within 30 days prior to enrollment Subject is anticipated to receive a renal transplant within 90 days (subjects can be on the transplant list, but a subject with a known or anticipated transplant date within the next 90 days should be excluded) Any other medical condition which renders the subject unable to or unlikely to complete the study, or which would interfere with optimal participation in the study or produce significant risk to the subject. -

Contacts/Locations


Study Officials:	Antony Pfaffle, MD Study Director Chief Scientific Officer
Locations:	United States, California
	Riverside Nephrology Physicians/Van Buren Dialysis center Riverside, California, United States, 92503
	North America Research Institute San Dimas, California, United States, 91773
	United States, Florida
	North Beach Dialysis Center Inc. Miami Gardens, Florida, United States, 33169
	United States, New York
	Lower Manhattan Dialysis Center New York, New York, United States, 10016
	United States, Texas
	Diagnostic Clinic of Houston Houston, Texas, United States, 77004

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:
Available IPD/Information:

Document Section


	Study Protocol Document Date: October 6, 2017 Uploaded: 04/28/2021 17:40 File Name: Prot_000.pdf
	Statistical Analysis Plan Document Date: January 29, 2018 Uploaded: 04/28/2021 17:41 File Name: SAP_001.pdf

Participant Flow

Recruitment Details

Pre-assignment Details

Arm/Group Title	Neutrolin Arm	Heparin Arm
Arm/Group Description	Neutrolin: Neutrolin will be added to the central venous catheter after dialysis as a lock solution Neutrolin: Neutrolin® will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session	Heparin: Heparin will be added to the central venous catheter after dialysis as a lock solution Heparin: Heparin will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session

Period Title: Overall Study
Started	403	403
Completed	359	359
Not Completed	44	44

Baseline Characteristics


Arm/Group Title		Neutrolin Arm	Heparin Arm	Total
Arm/Group Description		Neutrolin: Neutrolin will be added to the central venous catheter after dialysis as a lock solution Neutrolin: Neutrolin® will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session	Heparin: Heparin will be added to the central venous catheter after dialysis as a lock solution Heparin: Heparin will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session	Total of all reporting groups
Overall Number of Baseline Participants		403	403	806
Baseline Analysis Population Description
Age, Continuous Mean (Standard Deviation) Unit of measure: years	Number Analyzed	403 Participants	403 Participants	806 Participants
		60.8(14.22)	60.9(14.39)	60.9(14.30)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	403 Participants	403 Participants	806 Participants
	Female	184 45.66%	154 38.21%	338 41.94%
	Male	219 54.34%	249 61.79%	468 58.06%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	403 Participants	403 Participants	806 Participants
	American Indian or Alaska Native	3 0.74%	2 0.5%	5 0.62%
	Asian	15 3.72%	18 4.47%	33 4.09%
	Native Hawaiian or Other Pacific Islander	10 2.48%	4 0.99%	14 1.74%
	Black or African American	126 31.27%	112 27.79%	238 29.53%
	White	248 61.54%	262 65.01%	510 63.28%
	More than one race	0 0%	0 0%	0 0%
	Unknown or Not Reported	1 0.25%	5 1.24%	6 0.74%
Region of Enrollment Measure Type: Number Unit of measure: participants	Number Analyzed	403 Participants	403 Participants	806 Participants
United States		403	403	806

Outcome Measures

1. Primary Outcome:

Title

Presence of a CAC-Adjudicated Catheter-Related Bloodstream Infection (CRBSI) in Subjects Receiving Hemodialysis for the Treatment of End Stage Renal Disease (ESRD): Final Analysis

Description

CRBSI was defined as the same organism grown from at least one positive blood culture from a peripheral site or bloodline sample, or either the arterial or venous catheter hub. The final assessment of CRBSI was determined by a Clinical Adjudication Committee (CAC) who used both clinical documentation and blood culture results in their assessment.

Time Frame

The event time was the number of days from randomization until the occurrence of a CAC-Adjudicated CRBSI or until the subject was censored. The mean participant duration of exposure to study drug was 174 days (range 4-884 days).

Outcome Measure Data

Analysis Population Description

Full Analysis Population - all subjects randomized and receiving one or more doses of study medication.


Arm/Group Title	Neutrolin Arm	Heparin Arm
Arm/Group Description	Neutrolin: Neutrolin will be added to the central venous catheter after dialysis as a lock solution Neutrolin: Neutrolin® will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session	Heparin: Heparin will be added to the central venous catheter after dialysis as a lock solution Heparin: Heparin will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session
Overall Number of Participants Analyzed	397	398
Measure Type: Count of Participants Unit of Measure: Participants	9 2.3%	32 8%

Statistical Analysis 1


Statistical Analysis Overview	Comparison Group Selection	Neutrolin Arm, Heparin Arm
	Comments	The null hypothesis was that there was no difference in the survival functions for CRBSI between the two treatments. Based on 80% power to detect a 55% reduction in the risk of CRBSI relative to the control treatment, a 1:1 randomization, a 2-sided log-rank test, one interim analysis using the method of Pocock, and an overall alpha of 0.05, it was determined that 56 CRBSIs would be needed. These are the results of the final analysis.
	Type of Statistical Test	Superiority
	Comments	[Not specified]


Statistical Test of Hypothesis	P-Value	0.0006
	Comments	The threshold significance level at the interim and final statistical analyses for the primary efficacy endpoint was 0.0294.
	Method	Log Rank
	Comments	[Not specified]


Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.29
	Confidence Interval	(2-sided) 95% 0.14 to 0.62
	Estimation Comments	The numerator for the hazard ratio was the estimated hazard for the Neutrolin treatment arm, and the denominator was the estimated hazard for the Heparin treatment arm.

2. Secondary Outcome:

Title

Participants With a Study Catheter Removal for Any Reason

Description

Analysis of all catheter removals during the study or until the catheter was removed

Time Frame

The event time was the number of days from randomization until catheter removal for any reason or until the subject was censored. The mean participant duration of exposure to study drug was 174 days (range 4-884 days).

Outcome Measure Data

Analysis Population Description

Full Analysis Population - all subjects randomized and receiving one or more doses of study medication.


Arm/Group Title	Neutrolin Arm	Heparin Arm
Arm/Group Description	Neutrolin: Neutrolin will be added to the central venous catheter after dialysis as a lock solution Neutrolin: Neutrolin® will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session	Heparin: Heparin will be added to the central venous catheter after dialysis as a lock solution Heparin: Heparin will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session
Overall Number of Participants Analyzed	397	398
Measure Type: Count of Participants Unit of Measure: Participants	236 59.4%	225 56.5%

Statistical Analysis 1


Statistical Analysis Overview	Comparison Group Selection	Neutrolin Arm, Heparin Arm
	Comments	The null hypothesis was that there was no difference in the time until catheter removal for any reason between the two treatments.
	Type of Statistical Test	Superiority
	Comments	[Not specified]


Statistical Test of Hypothesis	P-Value	0.4161
	Comments	The threshold for statistical significance was p < 0.05.
	Method	Log Rank
	Comments	[Not specified]


Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-sided) 95% 0.90 to 1.29
	Estimation Comments	The numerator for the hazard ratio was the estimated hazard for the Neutrolin treatment arm, and the denominator was the estimated hazard for the Heparin treatment arm.

Adverse Events


Time Frame	Through a participant's study completion. The mean participant duration of exposure to study drug was 174 days (range 4-884 days).
Adverse Event Reporting Description	Adverse events were collected for all participants who received study drug, the Full Analysis Population (n=398 Neutrolin, n=399 Heparin). Subjects who did not receive study medication are not included in the adverse event reporting.

Arm/Group Title	Neutrolin Arm		Heparin Arm
Arm/Group Description	Neutrolin: Neutrolin will be added to the central venous catheter after dialysis as a lock solution Neutrolin: Neutrolin® will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session		Heparin: Heparin will be added to the central venous catheter after dialysis as a lock solution Heparin: Heparin will be instilled into central venous HD catheters at the discontinuation of all dialysis sessions and will be withdrawn prior to the initiation of the next dialysis session
All-Cause Mortality
	Neutrolin Arm		Heparin Arm
	Affected / At Risk (%)	# Events	Affected / At Risk (%)	# Events
Total	18 / 398 (4.52%)		21 / 399 (5.26%)
Serious Adverse Events
	Neutrolin Arm		Heparin Arm
	Affected / At Risk (%)	# Events	Affected / At Risk (%)	# Events
Total	159 / 398 (39.95%)		167 / 399 (41.85%)
Blood and lymphatic system disorders
Anemia ^{† A}	3 / 398 (0.75%)	3	4 / 399 (1%)	4
Hemorrhagic anemia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Heparin-induced thrombocytopenia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Lymphadenitis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Nephrogenic anemia ^{† A}	3 / 398 (0.75%)	3	4 / 399 (1%)	4
Normocytic anemia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Pancytopenia ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Thrombocytopenia ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Cardiac disorders
Acute coronary syndrome ^{† A}	1 / 398 (0.25%)	1	2 / 399 (0.5%)	2
Acute myocardial infarction ^{† A}	5 / 398 (1.26%)	5	13 / 399 (3.26%)	13
Angina pectoris ^{† A}	5 / 398 (1.26%)	5	5 / 399 (1.25%)	5
Angina unstable ^{† A}	0 / 398 (0%)	0	3 / 399 (0.75%)	3
Atrial fibrillation ^{† A}	2 / 398 (0.5%)	2	6 / 399 (1.5%)	6
Atrial tachycardia ^{† A}	0 / 398 (0%)	0	2 / 399 (0.5%)	2
Bradycardia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Cardiac arrest ^{† A}	2 / 398 (0.5%)	2	5 / 399 (1.25%)	5
Cardiac failure ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Cardiac failure acute ^{† A}	0 / 398 (0%)	0	2 / 399 (0.5%)	2
Cardiac failure congestive ^{† A}	12 / 398 (3.02%)	12	7 / 399 (1.75%)	7
Cardiac tamponade ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Cardiac valve disease ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Cardio-respiratory arrest ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Cardiomyopathy ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Coronary artery disease ^{† A}	2 / 398 (0.5%)	2	3 / 399 (0.75%)	3
Coronary artery occlusion ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Ischemic cardiomyopathy ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Left ventricular failure ^{† A}	1 / 398 (0.25%)	1	3 / 399 (0.75%)	3
Mitral valve incompetence ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Myocardial infarction ^{† A}	1 / 398 (0.25%)	1	3 / 399 (0.75%)	3
Nodal arrhythmia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pericardial effusion ^{† A}	1 / 398 (0.25%)	1	2 / 399 (0.5%)	2
Pulseless electrical activity ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Supraventricular tachycardia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Tachycardia ^{† A}	1 / 398 (0.25%)	1	2 / 399 (0.5%)	2
Congenital, familial and genetic disorders
Protein C deficiency ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Endocrine disorders
Hyperthyroidism secondary ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Myxoedema ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Eye disorders
Blindness cortical ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Visual impairment ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Gastrointestinal disorders
Abdominal pain ^{† A}	2 / 398 (0.5%)	2	4 / 399 (1%)	4
Abdominal pain upper ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Ascites ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Colitis ischemic ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Constipation ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Diabetic gastroparesis ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Diarrhea ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Dumping syndrome ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Duodenal ulcer ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Dysphagia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Esophageal ulcer hemorrhage ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Esophageal varices hemorrhage ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Esophagitis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Esophagitis ulcerative ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Gastric ulcer ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Gastric ulcer hemorrhage ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Gastritis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Gastrointestinal hemorrhage ^{† A}	4 / 398 (1.01%)	4	6 / 399 (1.5%)	6
Hematemesis ^{† A}	3 / 398 (0.75%)	3	1 / 399 (0.25%)	1
Hemorrhoidal hemorrhage ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Incarcerated inguinal hernia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Intestinal infarction ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Intestinal ischemia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Intestinal obstruction ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Large intestine perforation ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Lower gastrointestinal hemorrhage ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Mallory-Weiss syndrome ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Nausea ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pancreatitis ^{† A}	3 / 398 (0.75%)	3	0 / 399 (0%)	0
Pancreatitis acute ^{† A}	3 / 398 (0.75%)	3	0 / 399 (0%)	0
Peptic ulcer ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Small intestinal obstruction ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Upper gastrointestinal hemorrhage ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Vomiting ^{† A}	5 / 398 (1.26%)	5	1 / 399 (0.25%)	1
General disorders
Asthenia ^{† A}	3 / 398 (0.75%)	3	2 / 399 (0.5%)	2
Chest pain ^{† A}	1 / 398 (0.25%)	1	2 / 399 (0.5%)	2
Complication associated with device ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Death ^{† A}	5 / 398 (1.26%)	5	2 / 399 (0.5%)	2
Drug withdrawal syndrome ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Edema peripheral ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Impaired healing ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Multiple organ dysfunction syndrome ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Non-cardiac chest pain ^{† A}	5 / 398 (1.26%)	5	1 / 399 (0.25%)	1
Pain ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Pyrexia ^{† A}	0 / 398 (0%)	0	3 / 399 (0.75%)	3
Hepatobiliary disorders
Biliary diskynesia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Cholangitis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Cholecystitis ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Cholecystitis acute ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Cholecystitis chronic ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Cholelithiasis ^{† A}	3 / 398 (0.75%)	3	0 / 399 (0%)	0
Hemobilia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Hepatic cholestatic ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Hepatic cirrhosis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Hepatic failure ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Jaundice ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Jaundice cholestatic ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Immune system disorders
Hypogammaglobulinemia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Infections and infestations
Abdominal abscess ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Abscess neck ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Appendicitis perforated ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Arteriovenous fistula site infection ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Arteriovenous graft site infection ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Bacteremia ^{† A}	5 / 398 (1.26%)	5	7 / 399 (1.75%)	7
Bacterial sepsis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Bronchitis ^{† A}	2 / 398 (0.5%)	2	2 / 399 (0.5%)	2
Bronchitis bacterial ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Carbuncle ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Catheter site cellulitis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Cellulitis ^{† A}	7 / 398 (1.76%)	7	2 / 399 (0.5%)	2
Clostridium difficile colitis ^{† A}	1 / 398 (0.25%)	1	3 / 399 (0.75%)	3
Clostridium difficile infection ^{† A}	4 / 398 (1.01%)	4	0 / 399 (0%)	0
Device related infection ^{† A}	6 / 398 (1.51%)	6	8 / 399 (2.01%)	8
Device related sepsis ^{† A}	2 / 398 (0.5%)	2	4 / 399 (1%)	4
Diabetic foot infection ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Endocarditis ^{† A}	0 / 398 (0%)	0	2 / 399 (0.5%)	2
Endocarditis staphylococcal ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Endophthalmitis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Enterococcal bacteremia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Enterococcal infection ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Escherichia urinary tract infection ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Gangrene ^{† A}	3 / 398 (0.75%)	3	5 / 399 (1.25%)	5
Gastritis viral ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Gastroenteritis ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Gastroenteritis viral ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Histoplasmosis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Infected skin ulcer ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Infectious pleural effusion ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Influenza ^{† A}	2 / 398 (0.5%)	2	3 / 399 (0.75%)	3
Intervertebral discitis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Klebsiella bacteremia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Localized infection ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Necrotizing soft tissue infection ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Oral candidiasis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Orchitis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Oropharyngeal candidiasis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Osteomyelitis ^{† A}	4 / 398 (1.01%)	4	4 / 399 (1%)	4
Osteomyelitis acute ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Pancreatic abscess ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pneumococcal sepsis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pneumonia ^{† A}	12 / 398 (3.02%)	12	21 / 399 (5.26%)	21
Pneumonia haemophilus ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pneumonia staphylococcal ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Postoperative wound infection ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Psoas abscess ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pyelonephritis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pyelonephritis acute ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Respiratory tract infection viral ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Sepsis ^{† A}	9 / 398 (2.26%)	9	14 / 399 (3.51%)	14
Septic shock ^{† A}	5 / 398 (1.26%)	5	1 / 399 (0.25%)	1
Serratia bacteremia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Sinusitis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Staphylococcal infection ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Staphylococcal sepsis ^{† A}	1 / 398 (0.25%)	1	4 / 399 (1%)	4
Stenotrophomanas infection ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Streptococcal bacteremia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Streptococcal sepsis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Subcutaneous abscess ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Tracheobronchitis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Tuberculosis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Upper respiratory tract infection ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Urinary tract infection ^{† A}	2 / 398 (0.5%)	2	2 / 399 (0.5%)	2
Urinary tract infection bacterial ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Urosepsis ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Viral infection ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Viral sepsis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Injury, poisoning and procedural complications
Abdominal wound dehiscence ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Anemia postoperative ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Ankle fracture ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Arteriovenous fistula occlusion ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Arteriovenous fistula site complication ^{† A}	1 / 398 (0.25%)	1	3 / 399 (0.75%)	3
Arteriovenous fistula site hematoma ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Arteriovenous graft thrombosis ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Eschar ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Fall ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Femur fracture ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Foot fracture ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Fractured coccyx ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Fractured sacrum ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Gastrostomy failure ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Head injury ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Hip fracture ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Incision site hemorrhage ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Limb surgery ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Pneumothorax traumatic ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Post procedural complication ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Procedural hypotension ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Procedural pain ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pubis fracture ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pulmonary contusion ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Spinal compression fracture ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Subdural hematoma ^{† A}	0 / 398 (0%)	0	2 / 399 (0.5%)	2
Toxicity to various agents ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Transplant dysfunction ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Vascular access complication ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Vascular graft complication ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Investigations
Blood creatinine phosphokinase MB increased ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Blood culture positive ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Blood potassium increased ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Ejection fraction increased ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Hemoglobin decreased ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
International normalized ration increased ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Diabetic ketoacidosis ^{† A}	1 / 398 (0.25%)	1	3 / 399 (0.75%)	3
Failure to thrive ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Fluid overload ^{† A}	14 / 398 (3.52%)	14	12 / 399 (3.01%)	12
Gout ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Hyperglycemia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Hyperkalemia ^{† A}	10 / 398 (2.51%)	10	8 / 399 (2.01%)	8
Hyperosmolar state ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Hypoglycaemia ^{† A}	6 / 398 (1.51%)	6	6 / 399 (1.5%)	6
Hypovolemia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Lactic acidosis ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Metabolic acidosis ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Metabolic disorder ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Musculoskeletal and connective tissue disorders
Arthritis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Back pain ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Back pain ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Costochondritis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Intervertebral disc degeneration ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Intervertebral disc protrusion ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Joint effusion ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Lumbar spinal stenosis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Muscular weakness ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Musculoskeletal chest pain ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Myopathy ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pain in extremity ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Rotator cuff syndrome ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Spinal column stenosis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukemia ^{† A}	1 / 398 (0.25%)	1	4 / 399 (1%)	4
Lung neoplasm malignant ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Neoplasm malignant ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Small cell lung cancer ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Urine leiomyoma ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Nervous system disorders
Altered state of consciousness ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Autonomic nervous system imbalance ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Carotid artery occlusion ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Carpal tunnel syndrome ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Cerebellar hemorrhage ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Cerebellar stroke ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Cerebral hemorrhage ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Cerebral infarction ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Cerebral ischemia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Cerebrovascular accident ^{† A}	4 / 398 (1.01%)	4	5 / 399 (1.25%)	5
Dementia ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Dizziness ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Dizziness postural ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Encephalopathy ^{† A}	0 / 398 (0%)	0	3 / 399 (0.75%)	3
Guillain-Barre syndrome ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Headache ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Hemorrhage intracranial ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Hemorrhagic stroke ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Hepatic encephalopathy ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Hyperglycemic seizure ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Hypertensive encephalopathy ^{† A}	0 / 398 (0%)	0	2 / 399 (0.5%)	2
Hypoxic-ischemic encephalopathy ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Loss of consciousness ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Metabolic encephalopathy ^{† A}	2 / 398 (0.5%)	2	2 / 399 (0.5%)	2
Neuralgia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Paraesthesia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Posterior reversible encephalopathy syndrome ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Seizure ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Somnolence ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Syncope ^{† A}	4 / 398 (1.01%)	4	1 / 399 (0.25%)	1
Toxic encephalopathy ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Transient ischemic attack ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Product Issues
Device breakage ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Device dislocation ^{† A}	3 / 398 (0.75%)	3	1 / 399 (0.25%)	1
Device malfunction ^{† A}	6 / 398 (1.51%)	6	1 / 399 (0.25%)	1
Thrombosis in device ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Psychiatric disorders
Delirium ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Mental status changes ^{† A}	2 / 398 (0.5%)	2	5 / 399 (1.25%)	5
Suicidal ideation ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Renal and urinary disorders
Azotemia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
End stage renal disease ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Nephrolithiasis ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Renal failure ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Renal hematoma ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Reproductive system and breast disorders
Penile swelling ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Acute respiratory distress syndrome ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Acute respiratory failure ^{† A}	4 / 398 (1.01%)	4	1 / 399 (0.25%)	1
Asthma ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Bronchiectasis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Chronic obstructive pulmonary disease ^{† A}	6 / 398 (1.51%)	6	2 / 399 (0.5%)	2
Cough ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Dyspnea ^{† A}	2 / 398 (0.5%)	2	5 / 399 (1.25%)	5
Dyspnea exertional ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Epistaxis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Hemoptysis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Hypoxia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Pleural effusion ^{† A}	3 / 398 (0.75%)	3	1 / 399 (0.25%)	1
Pneumonia aspiration ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pneumonitis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pneumothorax ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Pulmonary edema ^{† A}	5 / 398 (1.26%)	5	4 / 399 (1%)	4
Pulmonary embolism ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Pulmonary hypertension ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Respiratory failure ^{† A}	7 / 398 (1.76%)	7	9 / 399 (2.26%)	9
Skin and subcutaneous tissue disorders
Decubitus ulcer ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Diabetic foot ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Skin ulcer ^{† A}	2 / 398 (0.5%)	2	0 / 399 (0%)	0
Swelling face ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Vascular disorders
Accelerated hypertension ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Angiopathy ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Aortic dissection ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Aortic stenosis ^{† A}	1 / 398 (0.25%)	1	2 / 399 (0.5%)	2
Arterial hemorrhage ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Arteriosclerosis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Dry gangrene ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Haematoma ^{† A}	1 / 398 (0.25%)	1	2 / 399 (0.5%)	2
Hypertension ^{† A}	4 / 398 (1.01%)	4	10 / 399 (2.51%)	10
Hypertensive crisis ^{† A}	2 / 398 (0.5%)	2	6 / 399 (1.5%)	6
Hypertensive emergency ^{† A}	0 / 398 (0%)	0	2 / 399 (0.5%)	2
Hypotension ^{† A}	6 / 398 (1.51%)	6	3 / 399 (0.75%)	3
Iliac artery occlusion ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Jugular vein thrombosis ^{† A}	1 / 398 (0.25%)	1	2 / 399 (0.5%)	2
Orthostatic hypotension ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Peripheral artery occlusion ^{† A}	1 / 398 (0.25%)	1	1 / 399 (0.25%)	1
Peripheral artery occlusive disease ^{† A}	2 / 398 (0.5%)	2	1 / 399 (0.25%)	1
Peripheral ischemia ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Peripheral vascular disorder ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Steal syndrome ^{† A}	4 / 398 (1.01%)	4	1 / 399 (0.25%)	1
Superior vena cava occlusion ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Thrombosis ^{† A}	1 / 398 (0.25%)	1	0 / 399 (0%)	0
Vasculitis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Vasoconstriction ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
Venous stenosis ^{† A}	0 / 398 (0%)	0	1 / 399 (0.25%)	1
†Indicates events were collected by systematic assessment. ATerm from vocabulary, MeDRA 21.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Neutrolin Arm		Heparin Arm
	Affected / At Risk (%)	# Events	Affected / At Risk (%)	# Events
Total	314 / 398 (78.89%)		315 / 399 (78.95%)
Blood and lymphatic system disorders
Anemia ^{† A}	8 / 398 (2.01%)	8	16 / 399 (4.01%)	16
Nephrogenic anemia ^{† A}	10 / 398 (2.51%)	10	8 / 399 (2.01%)	8
Cardiac disorders
Acute myocardial infarction ^{† A}	6 / 398 (1.51%)	6	14 / 399 (3.51%)	14
Angina pectoris ^{† A}	10 / 398 (2.51%)	10	8 / 399 (2.01%)	8
Atrial fibrillation ^{† A}	7 / 398 (1.76%)	7	13 / 399 (3.26%)	13
Bradycardia ^{† A}	12 / 398 (3.02%)	12	11 / 399 (2.76%)	11
Cardiac failure congestive ^{† A}	16 / 398 (4.02%)	16	10 / 399 (2.51%)	10
Tachycardia ^{† A}	11 / 398 (2.76%)	11	22 / 399 (5.51%)	22
Gastrointestinal disorders
Abdominal pain ^{† A}	20 / 398 (5.03%)	20	27 / 399 (6.77%)	27
Constipation ^{† A}	18 / 398 (4.52%)	18	17 / 399 (4.26%)	17
Diarrhea ^{† A}	38 / 398 (9.55%)	38	30 / 399 (7.52%)	30
Gastrointestinal hemorrhage ^{† A}	6 / 398 (1.51%)	6	8 / 399 (2.01%)	8
Nausea ^{† A}	26 / 398 (6.53%)	26	43 / 399 (10.78%)	43
Vomiting ^{† A}	24 / 398 (6.03%)	24	31 / 399 (7.77%)	31
General disorders
Asthenia ^{† A}	15 / 398 (3.77%)	15	12 / 399 (3.01%)	12
Catheter site erythema ^{† A}	7 / 398 (1.76%)	7	8 / 399 (2.01%)	8
Edema peripheral ^{† A}	9 / 398 (2.26%)	9	19 / 399 (4.76%)	19
Non-cardiac chest pain ^{† A}	10 / 398 (2.51%)	10	4 / 399 (1%)	4
Pain ^{† A}	7 / 398 (1.76%)	7	10 / 399 (2.51%)	10
Peripheral swelling ^{† A}	9 / 398 (2.26%)	9	9 / 399 (2.26%)	9
Pyrexia ^{† A}	15 / 398 (3.77%)	15	24 / 399 (6.02%)	24
Infections and infestations
Bacteremia ^{† A}	6 / 398 (1.51%)	6	9 / 399 (2.26%)	9
Bronchitis ^{† A}	9 / 398 (2.26%)	9	5 / 399 (1.25%)	5
Cellulitis ^{† A}	13 / 398 (3.27%)	13	14 / 399 (3.51%)	14
Device-related infection ^{† A}	10 / 398 (2.51%)	10	17 / 399 (4.26%)	17
Nasopharyngitis ^{† A}	8 / 398 (2.01%)	8	3 / 399 (0.75%)	3
Osteomyelitis ^{† A}	8 / 398 (2.01%)	8	5 / 399 (1.25%)	5
Pneumonia ^{† A}	18 / 398 (4.52%)	18	28 / 399 (7.02%)	28
Sepsis ^{† A}	11 / 398 (2.76%)	11	21 / 399 (5.26%)	21
Upper respiratory tract infection ^{† A}	8 / 398 (2.01%)	8	15 / 399 (3.76%)	15
Urinary tract infection ^{† A}	12 / 398 (3.02%)	12	15 / 399 (3.76%)	15
Injury, poisoning and procedural complications
Arteriovenous fistula site complication ^{† A}	13 / 398 (3.27%)	13	20 / 399 (5.01%)	20
Fall ^{† A}	17 / 398 (4.27%)	17	17 / 399 (4.26%)	17
Procedural hypotension ^{† A}	18 / 398 (4.52%)	18	18 / 399 (4.51%)	18
Metabolism and nutrition disorders
Fluid overload ^{† A}	26 / 398 (6.53%)	26	21 / 399 (5.26%)	21
Hyperkalemia ^{† A}	27 / 398 (6.78%)	27	26 / 399 (6.52%)	26
Hypoglycemia ^{† A}	14 / 398 (3.52%)	14	10 / 399 (2.51%)	10
Musculoskeletal and connective tissue disorders
Back pain ^{† A}	15 / 398 (3.77%)	15	17 / 399 (4.26%)	17
Muscle spasm ^{† A}	23 / 398 (5.78%)	23	36 / 399 (9.02%)	36
Pain in extremity ^{† A}	15 / 398 (3.77%)	15	22 / 399 (5.51%)	22
Nervous system disorders
Dizziness ^{† A}	22 / 398 (5.53%)	22	16 / 399 (4.01%)	16
Headache ^{† A}	22 / 398 (5.53%)	22	22 / 399 (5.51%)	22
Syncope ^{† A}	10 / 398 (2.51%)	10	4 / 399 (1%)	4
Product Issues
Device dislocation ^{† A}	9 / 398 (2.26%)	9	5 / 399 (1.25%)	5
Device malfunction ^{† A}	68 / 398 (17.09%)	68	47 / 399 (11.78%)	47
Device occlusion ^{† A}	9 / 398 (2.26%)	9	9 / 399 (2.26%)	9
Thrombosis in device ^{† A}	8 / 398 (2.01%)	8	16 / 399 (4.01%)	16
Psychiatric disorders
Insomnnia ^{† A}	9 / 398 (2.26%)	9	7 / 399 (1.75%)	7
Mental status changes ^{† A}	9 / 398 (2.26%)	9	12 / 399 (3.01%)	12
Respiratory, thoracic and mediastinal disorders
Cough ^{† A}	21 / 398 (5.28%)	21	30 / 399 (7.52%)	30
Dyspnea ^{† A}	19 / 398 (4.77%)	19	30 / 399 (7.52%)	30
Pleural effusion ^{† A}	9 / 398 (2.26%)	9	10 / 399 (2.51%)	10
Pulmonary edema ^{† A}	6 / 398 (1.51%)	6	8 / 399 (2.01%)	8
Respiratory failure ^{† A}	9 / 398 (2.26%)	9	13 / 399 (3.26%)	13
Skin and subcutaneous tissue disorders
Skin ulcer ^{† A}	10 / 398 (2.51%)	10	4 / 399 (1%)	4
Vascular disorders
Hypertension ^{† A}	27 / 398 (6.78%)	27	39 / 399 (9.77%)	39
Hypotension ^{† A}	35 / 398 (8.79%)	35	27 / 399 (6.77%)	27
†Indicates events were collected by systematic assessment. ATerm from vocabulary, MeDRA 21.0

Limitations and Caveats


[Not specified]

More Information


Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact:
Name/Official Title:	Head of Clinical Operations
Organization:	CorMedix Inc.
Phone:	908-517-9500
Email:	lmasson@cormedix.com