The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• Sodium-glucose co-transporter 2 inhibitors show promise in traditional trials for heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).
• The Coronavirus Disease 2019 pandemic necessitated innovative approaches to clinical research, including remote trial methodologies.

Purpose of the Study:

• To confirm the benefits of sodium-glucose co-transporter 2 inhibitors in a patient-centered, entirely remote clinical trial.
• To evaluate the efficacy of canagliflozin in improving symptoms of heart failure (HF) across different ejection fraction (EF) statuses and in patients with or without diabetes.

Main Methods:

• The CHIEF-HF trial (NCT04252287) randomized 476 participants with HF to canagliflozin (100 mg) or placebo in a double-blind, all-virtual format.
• The primary outcome was the change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS) at 12 weeks.
• Enrollment was stopped early due to shifting sponsor priorities, prior to unblinding.

Main Results:

• Canagliflozin demonstrated a statistically significant improvement in KCCQ TSS of 4.3 points compared to placebo at 12 weeks (95% CI, 0.8-7.8; P=0.016), meeting the primary endpoint.
• Benefits were consistent across subgroups, including patients with HFpEF, HFrEF, and those with or without diabetes.
• The trial successfully confirmed canagliflozin's efficacy in improving symptom burden in HF, irrespective of EF or diabetes status.

Conclusions:

• Canagliflozin effectively improves symptoms in patients with heart failure, regardless of ejection fraction or diabetes status.
• The CHIEF-HF trial serves as a successful model for conducting patient-centered, all-virtual clinical trials, demonstrating feasibility and efficacy in a remote setting.