Exogenous KETOne Supplements in Patients Hospitalized for Acute Heart Failure

NCT06653725 | Recruiting Phase 2 DMC

• 2 other identifiers: KETO-AHF1-10-72-63-24
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 8

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.

Conditions

Acute Heart Failure (AHF)

Keywords

Acute heart failure; Ketone supplements; Ketones; 3-hydroxybutyrate; 1,3-butanediol; six-minute walk test; win ratio

Outcome Measures

Primary Outcomes (1)

• Change in clinical benefit during 1,3-butanediol treatment versus placebo

  Clinical benefit is defined through a hierarchical composite endpoint, using a win ratio, from day 0 to 30 in all-cause death and time to death, number of and time to heart failure events, ≥30 meters increase in the change from baseline to follow-up at 30 days in the 6MWT, (iv) \>30% decrease in the change from baseline to follow-up at 30 days in NT-proBNP, and (v) % decrease in NT-proBNP (continuous variable). The primary endpoint will be evaluated using a win ratio, in an intention-to-treat approach, with participants analyzed within the treatment groups to which they were originally randomized. The win ratio method involves a pairwise hierarchical comparison of each participant against all others and is determined by dividing the total number of wins achieved by participants in the 1,3-butanediol group by the total number of losses.

  From baseline (day 0) to end of treatment (day 30)

Secondary Outcomes (15)

• Time to all-cause death

  From baseline (day 0) to end of treatment (day 30)

• Time to first heart failure event

  From baseline (day 0) to end of treatment (day 30)

• Change in six-minute walking distance

  From baseline (day 0) to end of treatment (day 30)

• Change in daily activity level

  From discharge, day 30, and end of treatment (day 30)

• Change in NT-proBNP

  From baseline (day 0) to discharge and end of treatment (day 30)

Other Outcomes (14)

• Length of index hospital stay

  From baseline (day 0) to end of treatment (day 30)

• Days alive out of hospital

  From baseline (day 0) to end of treatment (day 30)

• Subject experiencing improvement/deterioration in NYHA Class

  From baseline (day 0) to discharge, day 30, and end of treatment (day 30)

Study Arms (2)

1,3-butanediol

EXPERIMENTAL

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

Dietary Supplement: 1,3-butanediol

Placebo

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo

Interventions

1,3-butanediol DIETARY_SUPPLEMENT

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

1,3-butanediol

Placebo DIETARY_SUPPLEMENT

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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)
• Cardiogenic shock in INTERMACS level 1 or 2 (i.e. unstable hemodynamics despite inotropic/vasopressor therapy)
• Likelihood or current use of mechanical circulatory support
• Recent cardiac surgery within 3 days
• Ongoing severe infection or sepsis, severe anemia, acute exacerbation of chronic obstructive pulmonary disease, pulmonary embolism, or cerebrovascular accident
• Significant primary valvular disease (hemodynamically severe uncorrected primary cardiac valvular disease)
• Planned implantation of a cardiac resynchronization therapy device
• eGFR \<15 mL/min/1.73 m2 during current hospitalization (unless ongoing continuous renal replacement therapy) or recurring dialysis
• 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
• Type 1 diabetes
• Advanced liver disease (Child-Pugh class C)
• Dementia or other cognitive disorder making the patient unable to give informed consent
• Pregnancy or breastfeeding
• Inability to intake oral substances or severe dysphagia
• Significant gastrointestinal disease (i.e. severe inflammatory bowel disease or gastric ulcer)

Sponsors & Collaborators

• Aarhus University Hospital: lead
• Viborg Regional Hospital: collaborator
• Hospitalsenhed Vest, Herning: collaborator
• Odense University Hospital: collaborator
• Aalborg University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator
• Copenhagen University Hospital at Herlev: collaborator
• Amager Hospital: collaborator

Study Sites (8)

Department of Cardiology, Aalborg University Hospital

Aalborg, Denmark

NOT YET RECRUITING

Department of Cardiology, Aarhus University Hospital

Aarhus N, 8200, Denmark

RECRUITING

Department of Cardiology, Herlev-Gentofte Hospital

Copenhagen, Denmark

RECRUITING

Department of Cardiology, Rigshospitalet

Copenhagen, Denmark

NOT YET RECRUITING

Department of Cardiology, Gødstrup Hospital, Herning, Denmark

Herning, 7400, Denmark

RECRUITING

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

Hvidovre, Denmark

RECRUITING

Department of Cardiology, Odense University Hospital

Odense, 5000, Denmark

NOT YET RECRUITING

Department of Cardiology, Viborg Hospital

Viborg, 8800, Denmark

RECRUITING

MeSH Terms

Conditions

Ketosis

Interventions

1,3-butylene glycol

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Kristoffer Berg-Hansen, MD, PhD

  Department of Cardiology, Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristoffer Berg-Hansen, MD, PhD

CONTACT

+4560540700; krisbe@rm.dk

Henrik Wiggers, MD, PHD, DMSc

CONTACT

henrikwiggers@dadlnet.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients are randomized 1:1 to 1,3-butanediol or matching placebo treatment for 30 days.

Study Record Dates

• First Submitted: October 21, 2024
• First Posted: October 22, 2024
• Study Start: March 20, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: June 5, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (8)