Acute Heart Failure (AHF)Phase 2KETO-AHFNCT06653725
Exogenous KETOne Supplements in Patients Hospitalized for Acute Heart Failure
A Phase 2 study testing 1,3-butanediol in people with Acute Heart Failure (AHF), run by Aarhus University Hospital at 8 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Heart Failure (AHF)
- What is being tested?
- 1,3-butanediol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- 8 sitesDenmark
- Study dates
- 20 Mar 2025to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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)
Show all 19Show fewer
- 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)
- Adherent to a ketogenic diet within 30 days of enrollment
- Awaiting cardiac transplantation
- Very severe lung disease and/or treatment with continuous home oxygen therapy
- 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
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Henrik Wiggers, MD, PHD, DMSc contact
8 sites in 1 country
Denmark8 sites, 8 recruiting
- Not yet recruiting
Department of Cardiology, Aalborg University Hospital
Aalborg
Søren Vraa, MD, PhD, +4560540700, sov@rn.dk
Søren Vraa, MD, PhD
- Recruiting
Department of Cardiology, Aarhus University Hospital
Aarhus N, 8200
Kristoffer Berg-Hansen, MD, PhD, +4560540700, krisbe@rm.dk
Henrik Wiggers, MD, PhD, DMSc, henrikwiggers@dadlnet.dk
- Recruiting
Department of Cardiology, Herlev-Gentofte Hospital
Copenhagen
Morten Schou, MD, PhD, +4560540700, morten.schou.04@regionh.dk
Morten Schou, MD, PhD
- Not yet recruiting
Department of Cardiology, Rigshospitalet
Copenhagen
Jacob Eifer Møller, MD, PhD, DMSc, +4560540700, Jacob.Moeller1@rsyd.dk
Jacob Eifer Møller, MD, PhD, DMSc
- Recruiting
Department of Cardiology, Gødstrup Hospital, Herning, Denmark
Herning, 7400
Morten Böttcher, +4560540700, morboett@rm.dk
Morten Böttcher, MD, PhD
- Recruiting
Department of Cardiology, Copenhagen University Hospital - Amager and Hvidovre Hospital
Hvidovre
Jens Dahlgaard Hove, MD, PhD, +4560540700, Jens.Dahlgaard.Hove@regionh.dk
Jens Dahlgaard Hove, MD, PhD
- Not yet recruiting
Department of Cardiology, Odense University Hospital
Odense, 5000
Mikael Kjær Poulsen, MD, PhD, +4560540700, Mikael.Kjaer.Poulsen1@rsyd.dk
Mikael Kjær Poulsen, MD, PhD
- Recruiting
Department of Cardiology, Viborg Hospital
Viborg, 8800
Malene Hollingdal, MD, PhD, +4560540700, malene.hollingdal@midt.rm.dk
Malene Hollingdal, MD, PhD
About this study
Official title: Exogenous KETOne Supplements in Patients Hospitalized for Acute Heart Failure. A Randomized Clinical Trial (KETO-AHF)
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.
Read the 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)
- Being tested
- 1,3-butanediol, Placebo
- Keywords
- Acute heart failure, Ketone supplements, Ketones, 3-hydroxybutyrate, 1,3-butanediol, six-minute walk test, win ratio
- Medical subject headings
- Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1,3-butanediolDietary supplement
1,3-butanediol (Ketone-IQ®) 118 mL (33 g) servings trice daily
PlaceboDietary supplement
Taste-matched placebo (isovolumic, isoviscous water with stevia) 118 mL servings trice daily
| Study group | Role | What they receive |
|---|---|---|
| 1,3-butanediol | Experimental | 1,3-butanediol (Ketone-IQ®) 118 mL (33 g) servings trice daily Receives: Dietary Supplement: 1,3-butanediol |
| Placebo | Placebo comparator | Taste-matched placebo (isovolumic, isoviscous water with stevia) 118 mL servings trice daily Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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) \&gt;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.
Measured: From baseline (day 0) to end of treatment (day 30)
Secondary outcomes (15)
Time to all-cause death
Measured: From baseline (day 0) to end of treatment (day 30)
Time to first heart failure event
Measured: From baseline (day 0) to end of treatment (day 30)
Change in six-minute walking distance
Measured: From baseline (day 0) to end of treatment (day 30)
Change in daily activity level
When discharged, a wearable triaxial accelerometer will be placed around the wrist of the patient. The accelerometer will measure daily physical activity (milligravitational units) between discharge and 30-day follow-up.
Measured: From discharge, day 30, and end of treatment (day 30)
Change in NT-proBNP
Measured: From baseline (day 0) to discharge and end of treatment (day 30)
Change in KCCQ-12 total summary score
Measured: From baseline (day 0) to discharge and end of treatment (day 30)
Change in VAS dyspnea score
Measured: From baseline (day 0) to discharge and end of treatment (day 30)
Change in physical exertion score during six- minute walk test
Measured: From baseline (day 0) to discharge and end of treatment (day 30)
Change in systolic blood pressure
Measured: From baseline (day 0) to discharge and end of treatment (day 30)
Change in body weight
Measured: From baseline (day 0) to discharge and end of treatment (day 30)
Diuretic response
Diuretic response will be defined as Δ weight kg/[(total intravenous dose)/40mg] + [(total oral dose)/80mg)] furosemide or equivalent loop diuretic dose
Measured: From baseline (day 0) to discharge and end of treatment (day 30)
Cumulative dose of loop diuretic medication
Measured: From baseline (day 0) to discharge and end of treatment (day 30)
Need for inotropes
Measured: From baseline (day 0) to end of treatment (day 30)
Transfer to the intensive care unit
Measured: From baseline (day 0) to end of treatment (day 30)
Need for dialysis
Measured: From baseline (day 0) to end of treatment (day 30)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2024
- Study start20 Mar 2025
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Heart Failure (AHF)Studies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients are randomized 1:1 to 1,3-butanediol or matching placebo treatment for 30 days.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Viborg Regional Hospital, Hospitalsenhed Vest, Herning, Odense University Hospital, Aalborg University Hospital, Copenhagen University Hospital, Rigshospitalet, Copenhagen University Hospital at Herlev, Amager Hospital
- Responsible party
- Sponsor
- Investigators
- Kristoffer Berg-Hansen, MD, PhD, Principal investigator, Department of Cardiology, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06653725
- Sponsor's protocol ID
- KETO-AHF
- Other IDs
- 1-10-72-63-24
- Acronym
- KETO-AHF
- Status last verified
- Sep 2024
- First submitted
- 21 Oct 2024
- Last updated
- 5 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kodur N, Nguyen C, Tang WHW. Therapeutic Ketosis for Heart Failure: A State-of-the-Art Review. J Card Fail. 2025 Jul;31(7):1051-1061. doi: 10.1016/j.cardfail.2025.01.028. Epub 2025 Mar 3.
PubMed 40043832
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exogenous KETOne Supplements in Patients Hospitalized for Acute Heart Failure. A Randomized Clinical Trial (KETO-AHF)
- ClinicalTrials.gov ID
- NCT06653725
- Acronym / sponsor ID
- KETO-AHF / KETO-AHF
- Conditions
- Acute Heart Failure (AHF)
- Keywords
- Acute heart failure, Ketone supplements, Ketones, 3-hydroxybutyrate, 1,3-butanediol, six-minute walk test, win ratio
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Collaborators
- Viborg Regional Hospital, Hospitalsenhed Vest, Herning, Odense University Hospital, Aalborg University Hospital, Copenhagen University Hospital, Rigshospitalet, Copenhagen University Hospital at Herlev, Amager Hospital
- Study start
- 20 Mar 2025 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 22 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients are randomized 1:1 to 1,3-butanediol or matching placebo treatment for 30 days.
| Arm | Type | Receives |
|---|---|---|
| 1,3-butanediol | Experimental | Dietary Supplement: 1,3-butanediol1,3-butanediol (Ketone-IQ®) 118 mL (33 g) servings trice daily |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboTaste-matched placebo (isovolumic, isoviscous water with stevia) 118 mL servings trice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1,3-butanediol1,3-butanediol (Ketone-IQ®) 118 mL (33 g) servings trice daily | Dietary supplement | 1,3-butanediol |
| PlaceboTaste-matched placebo (isovolumic, isoviscous water with stevia) 118 mL servings trice daily | Dietary supplement | Placebo |
Primary outcome
Change in clinical benefit during 1,3-butanediol treatment versus placebo
Time frame: From baseline (day 0) to end of treatment (day 30)
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) \&gt;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.
15 secondary outcomes
Time to all-cause death
Time frame: From baseline (day 0) to end of treatment (day 30)
Time to first heart failure event
Time frame: From baseline (day 0) to end of treatment (day 30)
Change in six-minute walking distance
Time frame: From baseline (day 0) to end of treatment (day 30)
Change in daily activity level
Time frame: From discharge, day 30, and end of treatment (day 30)
Change in NT-proBNP
Time frame: From baseline (day 0) to discharge and end of treatment (day 30)
Change in KCCQ-12 total summary score
Time frame: From baseline (day 0) to discharge and end of treatment (day 30)
Change in VAS dyspnea score
Time frame: From baseline (day 0) to discharge and end of treatment (day 30)
Change in physical exertion score during six- minute walk test
Time frame: From baseline (day 0) to discharge and end of treatment (day 30)
Change in systolic blood pressure
Time frame: From baseline (day 0) to discharge and end of treatment (day 30)
Change in body weight
Time frame: From baseline (day 0) to discharge and end of treatment (day 30)
Diuretic response
Time frame: From baseline (day 0) to discharge and end of treatment (day 30)
Cumulative dose of loop diuretic medication
Time frame: From baseline (day 0) to discharge and end of treatment (day 30)
Need for inotropes
Time frame: From baseline (day 0) to end of treatment (day 30)
Transfer to the intensive care unit
Time frame: From baseline (day 0) to end of treatment (day 30)
Need for dialysis
Time frame: From baseline (day 0) to end of treatment (day 30)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- Derived from this study: PubMed 40043832Kodur N, Nguyen C, Tang WHW. Therapeutic Ketosis for Heart Failure: A State-of-the-Art Review. J Card Fail. 2025 Jul;31(7):1051-1061. doi: 10.1016/j.cardfail.2025.01.028. Epub 2025 Mar 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Henrik Wiggers, MD, PHD, DMSc contact
Kristoffer Berg-Hansen, MD, PhD principal investigator
Department of Cardiology, Aarhus University Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 1,3-butanediol in people with Acute Heart Failure (AHF), run by Aarhus University Hospital at 8 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kristoffer Berg-Hansen, MD, PhD (+4560540700, krisbe@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in clinical benefit during 1,3-butanediol treatment versus placebo (time frame: From baseline (day 0) to end of treatment (day 30)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06653725, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2025.