Exogenous KETOne Supplements in Patients Hospitalized for Acute Heart Failure

NCT ID: NCT06653725

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-20
• Study Completion Date: 2028-01-01

Brief 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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1,3-butanediol

1,3-butanediol (Ketone-IQ®) 118 mL (33 g) servings trice daily

Group Type: EXPERIMENTAL

1,3-butanediol

Intervention Type: DIETARY_SUPPLEMENT

1,3-butanediol (Ketone-IQ®) 118 mL (33 g) servings trice daily

Placebo

Taste-matched placebo (isovolumic, isoviscous water with stevia) 118 mL servings trice daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Taste-matched placebo (isovolumic, isoviscous water with stevia) 118 mL servings trice daily

Interventions

1,3-butanediol

1,3-butanediol (Ketone-IQ®) 118 mL (33 g) servings trice daily

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Taste-matched placebo (isovolumic, isoviscous water with stevia) 118 mL servings trice daily

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

The enrollment window extends to the first five days of the hospital stay.

Exclusion Criteria

1. Current hospitalization for AHF triggered by significant arrhythmia (atrial fibrillation/flutter with sustained ventricular response >110 beats per minute, clinically significant bradycardia, or sustained ventricular tachycardia)

2. Cardiogenic shock in INTERMACS level 1 or 2 (i.e. unstable hemodynamics despite inotropic/vasopressor therapy)

3. Likelihood or current use of mechanical circulatory support

4. Recent cardiac surgery within 3 days

5. Ongoing severe infection or sepsis, severe anemia, acute exacerbation of chronic obstructive pulmonary disease, pulmonary embolism, or cerebrovascular accident

6. Significant primary valvular disease (hemodynamically severe uncorrected primary cardiac valvular disease)

7. Planned implantation of a cardiac resynchronization therapy device

8. eGFR <15 mL/min/1.73 m2 during current hospitalization (unless ongoing continuous renal replacement therapy) or recurring dialysis

9. Known obstructive hypertrophic cardiomyopathy, congenital heart disease, acute mechanical cause of acute heart failure (e.g., papillary muscular rupture), acute myocarditis, or constrictive pericarditis according to the treating physician

10. Type 1 diabetes

11. Advanced liver disease (Child-Pugh class C)

12. Dementia or other cognitive disorder making the patient unable to give informed consent

13. Pregnancy or breastfeeding

14. Inability to intake oral substances or severe dysphagia

15. Significant gastrointestinal disease (i.e. severe inflammatory bowel disease or gastric ulcer)

16. Adherent to a ketogenic diet within 30 days of enrollment

17. Awaiting cardiac transplantation

18. Very severe lung disease and/or treatment with continuous home oxygen therapy

19. Major comorbidity, medical condition, or health issue that, according to the investigator's judgment, would hinder the participant's capacity to engage in or successfully finish the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Viborg Regional Hospital

OTHER

Sponsor Role: collaborator

Hospitalsenhed Vest, Herning

UNKNOWN

Sponsor Role: collaborator

Odense University Hospital

OTHER

Sponsor Role: collaborator

Aalborg University Hospital

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

Copenhagen University Hospital at Herlev

OTHER

Sponsor Role: collaborator

Copenhagen University Hospital, Amager-Hvidovre, Denmark

UNKNOWN

Sponsor Role: collaborator

Aarhus University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kristoffer Berg-Hansen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiology, Aarhus University Hospital

Locations

Department of Cardiology, Aalborg University Hospital

Aalborg, , Denmark

Site Status: NOT_YET_RECRUITING

Department of Cardiology, Aarhus University Hospital

Aarhus N, , Denmark

Site Status: RECRUITING

Department of Cardiology, Herlev-Gentofte Hospital

Copenhagen, , Denmark

Site Status: RECRUITING

Department of Cardiology, Rigshospitalet

Copenhagen, , Denmark

Site Status: NOT_YET_RECRUITING

Department of Cardiology, Gødstrup Hospital, Herning, Denmark

Herning, , Denmark

Site Status: RECRUITING

Department of Cardiology, Copenhagen University Hospital - Amager and Hvidovre Hospital

Hvidovre, , Denmark

Site Status: RECRUITING

Department of Cardiology, Odense University Hospital

Odense, , Denmark

Site Status: NOT_YET_RECRUITING

Department of Cardiology, Viborg Hospital

Viborg, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Kristoffer Berg-Hansen, MD, PhD

Role: CONTACT

krisbe@rm.dk

+4560540700

Henrik Wiggers, MD, PHD, DMSc

Role: CONTACT

henrikwiggers@dadlnet.dk

Facility Contacts

Søren Vraa, MD, PhD

Role: primary

sov@rn.dk

+4560540700

Kristoffer Berg-Hansen, MD, PhD

Role: primary

krisbe@rm.dk

+4560540700

Henrik Wiggers, MD, PhD, DMSc

Role: backup

henrikwiggers@dadlnet.dk

Morten Schou, MD, PhD

Role: primary

morten.schou.04@regionh.dk

+4560540700

Jacob Eifer Møller, MD, PhD, DMSc

Role: primary

Jacob.Moeller1@rsyd.dk

+4560540700

Morten Böttcher

Role: primary

morboett@rm.dk

+4560540700

Jens Dahlgaard Hove, MD, PhD

Role: primary

Jens.Dahlgaard.Hove@regionh.dk

+4560540700

Mikael Kjær Poulsen, MD, PhD

Role: primary

Mikael.Kjaer.Poulsen1@rsyd.dk

+4560540700

Malene Hollingdal, MD, PhD

Role: primary

malene.hollingdal@midt.rm.dk

+4560540700

Other Identifiers

1-10-72-63-24

Identifier Type: REGISTRY

Identifier Source: secondary_id

KETO-AHF

Identifier Type: -

Identifier Source: org_study_id