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NCT04252287: CHIEF-HF

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

Completed Phase 3 Results posted Last updated 30 March 2025
What this trial tests

Phase 3 trial testing Canagliflozin 100 mg in Heart Failure in 476 participants. Completed in 9 November 2021.

Timeline
10 March 2020
Primary endpoint
9 November 2021
9 November 2021

Quick facts

Lead sponsorJanssen Research & Development, LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment476
Start date10 March 2020
Primary completion9 November 2021
Estimated completion9 November 2021
Sites18 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

18 and older, any sex, with Heart Failure. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 12 Primary · 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 denotin

GroupValue95% CI
Placebo4.9± 1.27
Canagliflozin 100 mg9.2± 1.27
Change From Baseline in Total Daily Step Count at Week 12 Secondary · 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.

GroupValue95% CI
Placebo-74.9± 112.85
Canagliflozin 100 mg-45.1± 113.78
Change From Baseline in KCCQ Individual Domain Scores (Physical Limitation and Quality of Life) at Week 12 Secondary · 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 fo

KCCQ-Physical Limitation
GroupValue95% CI
Placebo4.8± 1.26
Canagliflozin 100 mg7.8± 1.27
KCCQ-Quality of Life
GroupValue95% CI
Placebo9.1± 1.40
Canagliflozin 100 mg12.4± 1.41
Change From Baseline in KCCQ Clinical Summary Score at Week 12 Secondary · 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

GroupValue95% CI
Placebo4.7± 1.16
Canagliflozin 100 mg8.5± 1.17
Change From Baseline in KCCQ Overall Summary Score at Week 12 Secondary · 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 1

GroupValue95% CI
Placebo6.2± 1.18
Canagliflozin 100 mg9.5± 1.18

Adverse events — posted to ClinicalTrials.gov

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). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 36/231 (16%)
Deaths: 5/231
Canagliflozin 100 mg
Serious: 33/224 (15%)
Deaths: 3/224

Serious adverse events (82 terms)

ReactionSystemPlaceboCanagliflozin 100 mg
Cardiac failure congestiveCardiac disorders
COVID-19Infections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
Chest painGeneral disorders
Peripheral swellingGeneral disorders
PneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
Oxygen saturation decreasedInvestigations
Cerebrovascular accidentNervous system disorders
HypotensionVascular disorders
AnaemiaBlood and lymphatic system disorders
ArrhythmiaCardiac disorders
Atrial flutterCardiac disorders
Cardiac arrestCardiac disorders
Cardiac failureCardiac disorders
Cardiac failure acuteCardiac disorders
Cardiogenic shockCardiac disorders
Coronary artery diseaseCardiac disorders
Coronary artery occlusionCardiac disorders
Intracardiac thrombusCardiac disorders
Pericardial effusionCardiac disorders
Ventricular tachycardiaCardiac disorders
GoitreEndocrine disorders
Visual impairmentEye disorders

Most-reported serious reactions: Cardiac failure congestive, COVID-19, Dyspnoea, Atrial fibrillation, Chest pain, Peripheral swelling, Pneumonia, Urinary tract infection.

Data from ClinicalTrials.gov NCT04252287 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial.
    Spertus JA, Birmingham MC, Nassif M, Damaraju CV, et al · · 2022 · cited 182× · PMID 35228753 · DOI 10.1038/s41591-022-01703-8
  2. The NO-cGMP-PKG Axis in HFpEF: From Pathological Mechanisms to Potential Therapies.
    Cai Z, Wu C, Xu Y, Cai J, et al · · 2023 · cited 33× · PMID 36818566 · DOI 10.14336/ad.2022.0523
  3. Novel Trial Design: CHIEF-HF.
    Spertus JA, Birmingham MC, Butler J, Lingvay I, et al · · 2021 · cited 22× · PMID 33724883 · DOI 10.1161/circheartfailure.120.007767
  4. Effects of SGLT2 inhibitors on cardiac function and health status in chronic heart failure: a systematic review and meta-analysis.
    Chen J, Jiang C, Guo M, Zeng Y, et al · · 2024 · cited 21× · PMID 38172861 · DOI 10.1186/s12933-023-02042-9
  5. Sodium-glucose cotransporter-2 inhibition for heart failure with preserved ejection fraction and chronic kidney disease with or without type 2 diabetes mellitus: a narrative review.
    Mentz RJ, Brunton SA, Rangaswami J. · · 2023 · cited 16× · PMID 37974185 · DOI 10.1186/s12933-023-02023-y
  6. Sodium-glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review.
    Rasalam R, Atherton JJ, Deed G, Molloy-Bland M, et al · · 2021 · cited 16× · PMID 34219407 · DOI 10.1002/ehf2.13483
  7. Association Between Wearable Device Measured Activity and Patient-Reported Outcomes for Heart Failure.
    Golbus JR, Gosch K, Birmingham MC, Butler J, et al · · 2023 · cited 15× · PMID 37498273 · DOI 10.1016/j.jchf.2023.05.033
  8. SGLT-2 inhibitors on prognosis and health-related quality of life in patients with heart failure and preserved ejection fraction: A systematic review and meta-analysis.
    Yang D, Zhang Y, Yan J, Liu M, et al · · 2022 · cited 12× · PMID 36158789 · DOI 10.3389/fcvm.2022.942125

Verify or expand the search:

Other trials of Canagliflozin 100 mg

Trials testing the same drug.

Other recruiting trials for Heart Failure

Currently open trials in the same condition.

Other Janssen Research & Development, LLC trials

Trials by the same sponsor.

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