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

• 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: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: January 31, 2020
• First Posted Date: February 5, 2020
• Results First Submitted Date: November 7, 2022
• Results First Posted Date: January 12, 2023
• Last Update Posted Date: January 12, 2023
• Actual Study Start Date: March 10, 2020
• Actual Primary Completion Date: November 9, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 7, 2022)

Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 12 [ Time Frame: Baseline, 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.

Original Primary Outcome Measures (submitted: January 31, 2020)

Change from Baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) to Week 12 [ Time Frame: Baseline to Week 12 ]

Change from baseline in KCCQ-TSS will be reported. The KCCQ is a 23-item, self-administered questionnaire with score range of 0 to 100, and higher scores indicating better health.

Current Secondary Outcome Measures (submitted: November 7, 2022)

• Change From Baseline in Total Daily Step Count at Week 12 [ Time Frame: Baseline, 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.
• Change From Baseline in KCCQ Individual Domain Scores (Physical Limitation and Quality of Life) at Week 12 [ Time Frame: Baseline, 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.
• Change From Baseline in KCCQ Clinical Summary Score at Week 12 [ Time Frame: Baseline, 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.
• Change From Baseline in KCCQ Overall Summary Score at Week 12 [ Time Frame: Baseline, 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.

Original Secondary Outcome Measures (submitted: January 31, 2020)

• Change in Total Daily Step Count from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
  Change from baseline in total daily step count will be reported. Step count will be measured from the Fitbit device data. The Fitbit app on the participant's phone will collect all data from the Fitbit device.
• Change from Baseline in KCCQ Individual Domain Scores to Week 12 [ Time Frame: Baseline to Week 12 ]
  The KCCQ is a 23-item self-administered questionnaire developed to independently measure the patient's perception of their health status over eight domains: physical limitation; symptom stability; symptom frequency; symptom burden; total symptom; social limitation; self-efficacy; and quality of life. Summary scores will be computed: the "Clinical Summary Score" including total symptom and physical limitation scores; and the "Overall Summary Score" including the total symptom, physical limitation, social limitations and quality of life scores. Scores are transformed into values ranging from 0 to 100, with higher scores indicating more favorable health status. Improvement in physical limitation, quality of life, clinical summary, and overall summary will be assessed.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure
• Official Title: Canagliflozin: Impact on Health Status, Quality of Life, and Functional Status in Heart Failure
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

• Drug: Canagliflozin 100 mg
  Participants will receive 100 mg immediate-release, over-encapsulated tablets (as a capsule) orally once daily.
  Other Names:

  • JNJ-28431754
  • INVOKANA
• Drug: Placebo
  Participants will receive matching placebo capsules orally once daily.

Study Arms

• 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.
  Intervention: Drug: Canagliflozin 100 mg
• Placebo Comparator: Placebo
  Participants will be administered matching placebo capsules orally once daily for 12 weeks.
  Intervention: Drug: Placebo

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 2, 2021): 476
• Original Estimated Enrollment (submitted: January 31, 2020): 1900
• Actual Study Completion Date: November 9, 2021
• Actual Primary Completion Date: November 9, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04252287
• Other Study ID Numbers: CR108750; 28431754HFA3002 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

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

• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: December 2022