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A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure (CHIEF-HF)

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ClinicalTrials.gov Identifier: NCT04252287
Recruitment Status : Completed
First Posted : February 5, 2020
Results First Posted : January 12, 2023
Last Update Posted : January 12, 2023
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: Canagliflozin 100 mg
Drug: Placebo
Enrollment 476
Recruitment Details  
Pre-assignment Details A total of 1,333 participants were screened. Of which, 476 participants were randomized in the study.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description Participants received placebo (matched to canagliflozin) capsule orally once daily for 12 weeks. Participants received canagliflozin 100 milligrams (mg) immediate-release, over-encapsulated tablet (as capsule) orally once daily for 12 weeks.
Period Title: Overall Study
Started 238 238
Treated (Safety Analysis Set) [1] 231 224
Completed 207 209
Not Completed 31 29
Reason Not Completed
Death             5             3
Lost to Follow-up             4             6
Withdrawal by Subject             19             16
Protocol Violation             3             4
[1]
Safety analysis set included all randomized participants who received at least 1 dose of study intervention.
Arm/Group Title Placebo Canagliflozin 100 mg Total
Hide Arm/Group Description Participants received placebo (matched to canagliflozin) capsule orally once daily for 12 weeks. Participants received canagliflozin 100 milligrams (mg) immediate-release, over-encapsulated tablet (as capsule) orally once daily for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 231 224 455
Hide Baseline Analysis Population Description
Safety analysis set included all randomized participants who received at least 1 dose of study intervention.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 231 participants 224 participants 455 participants
63.8  (13.5) 62.9  (13.15) 63.4  (13.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 231 participants 224 participants 455 participants
Female
99
  42.9%
105
  46.9%
204
  44.8%
Male
132
  57.1%
119
  53.1%
251
  55.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 231 participants 224 participants 455 participants
White
199
  86.1%
184
  82.1%
383
  84.2%
Black or African American
30
  13.0%
35
  15.6%
65
  14.3%
Asian
1
   0.4%
1
   0.4%
2
   0.4%
Other
1
   0.4%
4
   1.8%
5
   1.1%
1.Primary Outcome
Title Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 12
Hide Description Change from baseline in KCCQ-TSS was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-TSS was average of domains- symptom frequency and symptom burden, and transformed to a single score which ranged from 0 (worst) to 100 (the best possible status), where the higher score reflected better health status.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants who had received at least one dose of study intervention/medication and had at least one post-baseline KCCQ measurement. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received placebo (matched to canagliflozin) capsule orally once daily for 12 weeks.
Participants received canagliflozin 100 milligrams (mg) immediate-release, over-encapsulated tablet (as capsule) orally once daily for 12 weeks.
Overall Number of Participants Analyzed 206 208
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
4.9  (1.27) 9.2  (1.27)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.3
Confidence Interval (2-Sided) 95%
0.8 to 7.8
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Total Daily Step Count at Week 12
Hide Description Change from baseline in total daily step count at Week 12 was reported in this outcome measure. The number of steps taken per day was measured using a step activity monitor at baseline and throughout the study. Step count was measured from the Fitbit device data. The Fitbit app on the participant's phone collected all data from the Fitbit device. A negative change from baseline indicated a decrease in the number of daily steps.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who had received at least one dose of study intervention/medication and had at least one post-baseline KCCQ measurement. Here, N (Overall number of participants analyzed) signifies participants evaluated for this outcome measure.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received placebo (matched to canagliflozin) capsule orally once daily for 12 weeks.
Participants received canagliflozin 100 milligrams (mg) immediate-release, over-encapsulated tablet (as capsule) orally once daily for 12 weeks.
Overall Number of Participants Analyzed 208 205
Least Squares Mean (Standard Error)
Unit of Measure: Daily step count
-74.9  (112.85) -45.1  (113.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.852
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 29.8
Confidence Interval (2-Sided) 95%
-284.4 to 344.1
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in KCCQ Individual Domain Scores (Physical Limitation and Quality of Life) at Week 12
Hide Description Change from baseline in KCCQ physical limitation score and KCCQ quality of life score were reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 (worst) and 100 (the best possible status), where the higher score reflected better health status.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who had received at least one dose of study intervention/medication and had at least one post-baseline KCCQ measurement. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants with available data for each specified category.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received placebo (matched to canagliflozin) capsule orally once daily for 12 weeks.
Participants received canagliflozin 100 milligrams (mg) immediate-release, over-encapsulated tablet (as capsule) orally once daily for 12 weeks.
Overall Number of Participants Analyzed 206 208
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
KCCQ-Physical Limitation Number Analyzed 206 participants 204 participants
4.8  (1.26) 7.8  (1.27)
KCCQ-Quality of Life Number Analyzed 206 participants 208 participants
9.1  (1.40) 12.4  (1.41)
4.Secondary Outcome
Title Change From Baseline in KCCQ Clinical Summary Score at Week 12
Hide Description Change from baseline in KCCQ-clinical summary score was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-clinical summary score was average of domains- physical limitation and total symptoms (average of symptom frequency and symptom burden), and transformed to a single score which ranged from 0 (worst) -100 (the best possible status), where the higher score reflected better health status.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who had received at least one dose of study intervention/medication and had at least one post-baseline KCCQ measurement. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received placebo (matched to canagliflozin) capsule orally once daily for 12 weeks.
Participants received canagliflozin 100 milligrams (mg) immediate-release, over-encapsulated tablet (as capsule) orally once daily for 12 weeks.
Overall Number of Participants Analyzed 206 208
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
4.7  (1.16) 8.5  (1.17)
5.Secondary Outcome
Title Change From Baseline in KCCQ Overall Summary Score at Week 12
Hide Description Change from baseline in KCCQ-overall summary score was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ- overall summary score was average of domains- physical limitation, total symptoms (average of symptom frequency and symptom burden), quality of life, and social limitation, and transformed to a single score which ranged from 0 (worst) -100 (the best possible status), where the higher score reflected better health status.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who had received at least one dose of study intervention/medication and had at least one post-baseline KCCQ measurement. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received placebo (matched to canagliflozin) capsule orally once daily for 12 weeks.
Participants received canagliflozin 100 milligrams (mg) immediate-release, over-encapsulated tablet (as capsule) orally once daily for 12 weeks.
Overall Number of Participants Analyzed 206 208
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
6.2  (1.18) 9.5  (1.18)
Time Frame All-cause mortality: Up to 9 months; serious adverse events and other adverse events: Up to 30 days after end of treatment (up to 4 months)
Adverse Event Reporting Description Safety analysis set included all randomized participants who received at least 1 dose of study intervention.
 
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description Participants received placebo (matched to canagliflozin) capsule orally once daily for 12 weeks. Participants received canagliflozin 100 milligrams (mg) immediate-release, over-encapsulated tablet (as capsule) orally once daily for 12 weeks.
All-Cause Mortality
Placebo Canagliflozin 100 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   5/231 (2.16%)   3/224 (1.34%) 
Hide Serious Adverse Events
Placebo Canagliflozin 100 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   36/231 (15.58%)   33/224 (14.73%) 
Blood and lymphatic system disorders     
Anaemia * 1  0/231 (0.00%)  1/224 (0.45%) 
Cardiac disorders     
Arrhythmia * 1  1/231 (0.43%)  0/224 (0.00%) 
Atrial fibrillation * 1  2/231 (0.87%)  2/224 (0.89%) 
Atrial flutter * 1  0/231 (0.00%)  1/224 (0.45%) 
Cardiac arrest * 1  1/231 (0.43%)  0/224 (0.00%) 
Cardiac failure * 1  1/231 (0.43%)  0/224 (0.00%) 
Cardiac failure acute * 1  0/231 (0.00%)  1/224 (0.45%) 
Cardiac failure congestive * 1  3/231 (1.30%)  4/224 (1.79%) 
Cardiogenic shock * 1  0/231 (0.00%)  1/224 (0.45%) 
Coronary artery disease * 1  1/231 (0.43%)  0/224 (0.00%) 
Coronary artery occlusion * 1  1/231 (0.43%)  0/224 (0.00%) 
Intracardiac thrombus * 1  0/231 (0.00%)  1/224 (0.45%) 
Pericardial effusion * 1  1/231 (0.43%)  0/224 (0.00%) 
Ventricular tachycardia * 1  0/231 (0.00%)  1/224 (0.45%) 
Endocrine disorders     
Goitre * 1  0/231 (0.00%)  1/224 (0.45%) 
Eye disorders     
Visual impairment * 1  0/231 (0.00%)  1/224 (0.45%) 
Gastrointestinal disorders     
Gastric ulcer * 1  0/231 (0.00%)  1/224 (0.45%) 
Gastrointestinal haemorrhage * 1  1/231 (0.43%)  1/224 (0.45%) 
Oesophageal stenosis * 1  1/231 (0.43%)  0/224 (0.00%) 
Pancreatitis * 1  0/231 (0.00%)  1/224 (0.45%) 
General disorders     
Asthenia * 1  0/231 (0.00%)  1/224 (0.45%) 
Chest pain * 1  2/231 (0.87%)  0/224 (0.00%) 
Fatigue * 1  1/231 (0.43%)  1/224 (0.45%) 
Oedema * 1  1/231 (0.43%)  0/224 (0.00%) 
Pain * 1  0/231 (0.00%)  1/224 (0.45%) 
Peripheral swelling * 1  1/231 (0.43%)  2/224 (0.89%) 
Sudden cardiac death * 1  1/231 (0.43%)  0/224 (0.00%) 
Ulcer haemorrhage * 1  0/231 (0.00%)  1/224 (0.45%) 
Hepatobiliary disorders     
Cholelithiasis * 1  1/231 (0.43%)  0/224 (0.00%) 
Infections and infestations     
COVID-19 * 1  2/231 (0.87%)  4/224 (1.79%) 
Pneumonia * 1  2/231 (0.87%)  0/224 (0.00%) 
Pneumonia viral * 1  0/231 (0.00%)  1/224 (0.45%) 
Urinary tract infection * 1  0/231 (0.00%)  2/224 (0.89%) 
Urosepsis * 1  0/231 (0.00%)  1/224 (0.45%) 
Injury, poisoning and procedural complications     
Back injury * 1  1/231 (0.43%)  0/224 (0.00%) 
Fall * 1  0/231 (0.00%)  1/224 (0.45%) 
Foot fracture * 1  1/231 (0.43%)  0/224 (0.00%) 
Head injury * 1  0/231 (0.00%)  1/224 (0.45%) 
Hip fracture * 1  1/231 (0.43%)  1/224 (0.45%) 
Lower limb fracture * 1  1/231 (0.43%)  0/224 (0.00%) 
Road traffic accident * 1  0/231 (0.00%)  1/224 (0.45%) 
Tendon rupture * 1  1/231 (0.43%)  0/224 (0.00%) 
Investigations     
Blood creatinine increased * 1  0/231 (0.00%)  1/224 (0.45%) 
Blood glucose increased * 1  1/231 (0.43%)  0/224 (0.00%) 
Fibrin D dimer increased * 1  0/231 (0.00%)  1/224 (0.45%) 
Heart rate increased * 1  1/231 (0.43%)  0/224 (0.00%) 
Oxygen saturation decreased * 1  2/231 (0.87%)  0/224 (0.00%) 
Weight increased * 1  1/231 (0.43%)  1/224 (0.45%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  0/231 (0.00%)  1/224 (0.45%) 
Fluid overload * 1  0/231 (0.00%)  1/224 (0.45%) 
Fluid retention * 1  1/231 (0.43%)  0/224 (0.00%) 
Hypercalcaemia * 1  0/231 (0.00%)  1/224 (0.45%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  0/231 (0.00%)  1/224 (0.45%) 
Pain in extremity * 1  0/231 (0.00%)  1/224 (0.45%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant * 1  0/231 (0.00%)  1/224 (0.45%) 
Nervous system disorders     
Balance disorder * 1  1/231 (0.43%)  0/224 (0.00%) 
Bell's palsy * 1  1/231 (0.43%)  0/224 (0.00%) 
Cerebrovascular accident * 1  1/231 (0.43%)  2/224 (0.89%) 
Dizziness * 1  0/231 (0.00%)  1/224 (0.45%) 
Neuropathy peripheral * 1  1/231 (0.43%)  1/224 (0.45%) 
Psychiatric disorders     
Hallucination * 1  1/231 (0.43%)  0/224 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  1/231 (0.43%)  0/224 (0.00%) 
Renal impairment * 1  1/231 (0.43%)  0/224 (0.00%) 
Urinary retention * 1  0/231 (0.00%)  1/224 (0.45%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome * 1  1/231 (0.43%)  0/224 (0.00%) 
Asthma * 1  1/231 (0.43%)  0/224 (0.00%) 
Choking * 1  1/231 (0.43%)  0/224 (0.00%) 
Chronic obstructive pulmonary disease * 1  1/231 (0.43%)  0/224 (0.00%) 
Dyspnoea * 1  3/231 (1.30%)  1/224 (0.45%) 
Epistaxis * 1  0/231 (0.00%)  1/224 (0.45%) 
Haemoptysis * 1  0/231 (0.00%)  1/224 (0.45%) 
Pleural effusion * 1  1/231 (0.43%)  0/224 (0.00%) 
Pneumonitis * 1  1/231 (0.43%)  0/224 (0.00%) 
Pulmonary embolism * 1  0/231 (0.00%)  1/224 (0.45%) 
Pulmonary hypertension * 1  1/231 (0.43%)  0/224 (0.00%) 
Respiratory failure * 1  1/231 (0.43%)  0/224 (0.00%) 
Surgical and medical procedures     
Cardiac operation * 1  0/231 (0.00%)  1/224 (0.45%) 
Implantable defibrillator replacement * 1  1/231 (0.43%)  0/224 (0.00%) 
Knee arthroplasty * 1  1/231 (0.43%)  0/224 (0.00%) 
Vascular disorders     
Hypertension * 1  0/231 (0.00%)  1/224 (0.45%) 
Hypotension * 1  2/231 (0.87%)  1/224 (0.45%) 
Subclavian artery stenosis * 1  0/231 (0.00%)  1/224 (0.45%) 
1
Term from vocabulary, MedDRA Version 24.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Canagliflozin 100 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/231 (0.00%)   0/224 (0.00%) 
[Not Specified]
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 an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director CVM Health Equity
Organization: Janssen Scientific Affairs, LLC
Phone: 844-434-4210
EMail: ClinicalTrialDisclosure@its.jnj.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04252287    
Other Study ID Numbers: CR108750
28431754HFA3002 ( Other Identifier: Janssen Research & Development, LLC )
First Submitted: January 31, 2020
First Posted: February 5, 2020
Results First Submitted: November 7, 2022
Results First Posted: January 12, 2023
Last Update Posted: January 12, 2023