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

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

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).

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Canagliflozin 100 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 476
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Fort Smith, Arkansas, United States, 72903
      • Mercy Clinic Cardiology - Fort Smith
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado - Anschutz Medical Campus
  • Florida
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular Consultants
  • Georgia
    • Atlanta, Georgia, United States, 30022
      • Emory University
  • Idaho
    • Boise, Idaho, United States, 83712
      • St Lukes Regional Medical
  • Illinois
    • Peoria, Illinois, United States, 61614
      • OSF HealthCare Cardiovascular Institute
    • Winfield, Illinois, United States, 60190
      • Central DuPage Hospital
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Cancer Institute
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • MedStar Health Research Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital Kansas City
    • Washington, Missouri, United States, 63090
      • Mercy Health Research
  • New Jersey
    • Piscataway, New Jersey, United States, 08854
      • Robert Wood Johnson Medical School Dept. of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Texas
    • Corpus Christi, Texas, United States, 78412
      • Thomas Spann Clinic
    • Houston, Texas, United States, 30322
      • Texas Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Canagliflozin 100 mg; 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; Participants will receive 100 mg immediate-release, over-encapsulated tablets (as a capsule) orally once daily.; Other Names: INVOKANA; JNJ-28431754
Placebo Comparator: Placebo; Participants will be administered matching placebo capsules orally once daily for 12 weeks.	Drug: Placebo; Participants will receive matching placebo capsules orally once daily.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Spertus JA, Birmingham MC, Nassif M, Damaraju CV, Abbate A, Butler J, Lanfear DE, Lingvay I, Kosiborod MN, Januzzi JL. The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial. Nat Med. 2022 Apr;28(4):809-813. doi: 10.1038/s41591-022-01703-8. Epub 2022 Feb 28.
• Spertus JA, Birmingham MC, Butler J, Lingvay I, Lanfear DE, Abbate A, Kosiborod ML, Fawcett C, Burton P, Damaraju CV, Januzzi JL, Whang J. Novel Trial Design: CHIEF-HF. Circ Heart Fail. 2021 Mar;14(3):e007767. doi: 10.1161/CIRCHEARTFAILURE.120.007767. Epub 2021 Mar 16. Erratum In: Circ Heart Fail. 2021 Apr;14(4):e000068.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2020
• Primary Completion (Actual): November 9, 2021
• Study Completion (Actual): November 9, 2021

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: January 31, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Canagliflozin
• Other Study ID Numbers: CR108750; 28431754HFA3002 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No