A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to determine the superiority of the effectiveness of canagliflozin 100 milligram (mg) daily versus placebo in participants with symptomatic heart failure (HF) in improving the overall Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS).

Official Title
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Canagliflozin: Impact on Health Status, Quality of Life, and Functional Status in Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Canagliflozin 100 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Have clinically stable symptomatic heart failure (HF) (heart failure with reduced ejection fraction [HFrEF] and heart failure with preserved ejection fraction [HFpEF]): (A) For HFrEF: (a) ejection fraction (EF) less than or equal to (<=) 40 percent (%) and (b) a primary diagnosis of HF OR 2 medical visits (including virtual) with a HF diagnosis code in any position in the past 18 months (B) For HFpEF: (a) EF greater than (>) 40%; (b) a primary diagnosis of HF OR 2 medical visits (including virtual) with a HF diagnosis code in any position in the past 18 months, AND; (C) on a loop diuretic or spironolactone or eplerenone (mineralocorticoid receptor antagonists), in the past 18 months Have a baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) score of less than or equal to (<=) 80 prior to randomization Be able to read and understand English Possess and have sole use (example: not shared with other users) of smartphone compatible with the Fitbit device Willing/able to wear the Fitbit device on a regular basis for the 9-month study period Exclusion Criteria: Currently taking a sodium-glucose co-transporter 2 inhibitor (SGLT2i) or within the last 3 months History of diabetic ketoacidosis or have type 1 diabetes mellitus (T1DM) Have acute decompensated HF (exacerbation of symptomatic HF) requiring intravenous diuretics, inotropes, or vasodilators within the last 4 weeks Have stage 4 or 5 Chronic Kidney Disease (that is, estimated glomerular filtration rate [eGFR] <30 milliliter per minute [ml/min] on dialysis) from the most recent assessment Have a diagnosis of hypotension within 30 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canagliflozin 100 mg<br>Participants will be administered 100 milligram (mg) immediate-release, over-encapsulated tablets (as a capsule) orally once daily for 12 weeks. | Drug: Canagliflozin 100 mg<br>* Participants will receive 100 mg immediate-release, over-encapsulated tablets (as a capsule) orally once daily.<br>* Other names: INVOKANA;|
| Placebo Comparator: Placebo<br>Participants will be administered matching placebo capsules orally once daily for 12 weeks. | Drug: Placebo<br>* Participants will receive matching placebo capsules orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 12 | 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. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Daily Step Count at Week 12 | 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. | Baseline, Week 12 | 
| Change From Baseline in KCCQ Individual Domain Scores (Physical Limitation and Quality of Life) at Week 12 | 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. | Baseline, Week 12 | 
| Change From Baseline in KCCQ Clinical Summary Score at Week 12 | 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. | Baseline, Week 12 | 
| Change From Baseline in KCCQ Overall Summary Score at Week 12 | 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. | Baseline, Week 12 |