NCT06653725

Exogenous KETOne Supplements in Patients Hospitalized for Acute Heart Failure

Exogenous KETOne Supplements in Patients Hospitalized for Acute Heart Failure. A Randomized Clinical Trial (KETO-AHF)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 250 (estimated)
• Sponsor: Aarhus University Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, randomized, double-blind, placebo-controlled trial to investigate the clinical efficacy of treatment with exogenous dietary ketone supplement containing 1,3-butanediol in patients hospitalized with acute heart failure (AHF), potentially leading to better clinical outcomes.

Detailed description

Acute heart failure (AHF) is life-threatening with a 30-day mortality rate between 10% and 50%, especially in patients with cardiogenic shock. Current medical treatments have not shown a survival benefit in randomized trials, highlighting the need for new therapies. Ketone bodies, particularly 3-hydroxybutyrate (3-OHB), are vital for energy in the heart and brain during stress. Elevated 3-OHB levels from exogenous sources, such as ketone esters or 1,3-butanediol, enhance organ perfusion and improve cardiac function. In chronic heart failure (HF), 3-OHB infusion increases cardiac output and left ventricular ejection fraction (LVEF) without excess oxygen consumption, supporting its role as an efficient energy source. Short-term ketone ester treatment has been shown to improve hemodynamics, reduce NT-proBNP, and enhance physical performance in heart failure with reduced ejection fraction (HFrEF) patients. In AHF patients, ketone ester improved cardiac output, LVEF, and filling pressures. Emerging evidence suggests that 1,3-butanediol supplements may sustain ketosis longer, offering potential for practical dosing in the acute phase of heart failure. This proposal aims to study the clinical efficacy of treatment with exogenous dietary ketone supplement containing 1,3-butanediol in patients hospitalized with AHF. The primary hypothesis is that in patients hospitalized with AHF, a 30-day treatment with 1,3- butanediol has beneficial clinical effects as compared with placebo. Clinical benefit is defined as a hierarchical composite of death, heart failure (HF) events, change from baseline in the 6-minute walk test (6MWT), and change from baseline in NT-proBNP at 30 days, as assessed using win ratio statistics.

Conditions

• Acute Heart Failure (AHF)

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	1,3-butanediol	1,3-butanediol (Ketone-IQ®) 118 mL (33 g) servings trice daily
DIETARY_SUPPLEMENT	Placebo	Taste-matched placebo (isovolumic, isoviscous water with stevia) 118 mL servings trice daily

Timeline

• Start date: 2025-03-20
• Primary completion: 2027-11-01
• Completion: 2028-01-01
• First posted: 2024-10-22
• Last updated: 2025-06-05

Locations

8 sites across 1 country: Denmark