Acute Heart FailureKETO-AHFNCT07434466
Ketone Ester for Treatment Of Acute Heart Failure
A study testing Ketone Ester (KetoneAid MonoEster) in people with Acute Heart Failure, run by University of Alberta at 1 site in Canada.
Trial summary
Ketones have been suggested to have significant physiological effects in patients with heart failure. Potential mechanisms for these effects include energy provision for the failing heart and direct protective effects on other organs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Heart Failure
- What is being tested?
- Ketone Ester (KetoneAid MonoEster)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2027to Mar 2028
- Phase
- Interventional
- 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
Domain-Specific Inclusion Criteria:
- Primary diagnosis of AHF with dyspnea on exertion or at rest, and at least two of the following: congestion on chest radiograph, rales on chest auscultation, clinically relevant edema, or an elevated jugular venous pressure [21]
- Admitted to the hospital for less than 48 hours
- Estimated glomerular filtration rate above 15 mL/min/1.73m²
- NT-proBNP ≥ 1000 pg/ml
Domain-Specific Exclusion Criteria:
- Type 1 diabetes mellitus
- Patients on mechanical circulatory support
- Patients on more than one inotrope or on inopressors
- Patients on dialysis
- Patients with non-functioning enteral tracks
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: KETO-AHF: Ketone Ester for Treatment Of Acute Heart Failure: A Vanguard Randomized Controlled Trial
Ketones have been suggested to have significant physiological effects in patients with heart failure. Potential mechanisms for these effects include energy provision for the failing heart and direct protective effects on other organs. Despite the strong physiological rationale, the acute effects of ketone therapy in patients with acute heart failure (AHF) is unclear. AHF is a major healthcare issue, with in-hospital mortality exceeding 10%. Therefore, we propose a vanguard randomized controlled trial to assess the effects of ketone esters in patients with AHF. Sixty patients hospitalized with AHF will be randomized to receive either 25 grams of ketone esters three times per day or a matching placebo for five days, or until death or hospital discharge. We hypothesize that ketone therapy will improve markers of systemic congestion and heart failure symptoms. Primary endpoint will be changes in NT-proBNP levels during therapy. Secondary endpoints will be KCCQ scores, and hemodynamic profile as assessed by echocardiogram. Exploratory endpoints will clinical outcomes including mortality, need for intensive care unit admission, among others.
Read the detailed description
KETO-AHF (Ketone Ester for Treatment of Acute Heart Failure) is a single-site, double-blind, randomized, placebo-controlled vanguard clinical trial evaluating the feasibility, safety, and preliminary efficacy of exogenous ketone ester therapy in adults hospitalized with acute heart failure (AHF). The trial is conducted as a domain within the Heart Failure Efficacy and Research Trial (HEART) Platform master protocol framework.
Adults (≥18 years) admitted with a primary diagnosis of acute heart failure will be screened and enrolled within 48 hours of hospital admission. Eligible participants must have dyspnea and clinical evidence of congestion and meet protocol-specified laboratory and clinical criteria, including elevated NT-proBNP and adequate kidney function (eGFR >15 mL/min/1.73m²). Key exclusions include type 1 diabetes mellitus, dialysis dependence, inability to tolerate enteral therapy, and need for advanced mechanical circulatory support or inopressor therapy.
Participants will be randomized 1:1 to receive ketone ester therapy or matching placebo for up to 5 consecutive days (or until hospital discharge or death), in addition to standard-of-care acute heart failure management. Randomization will occur through a centralized web-based system using stratified randomization by sex, and both participants and study staff will remain blinded to allocation.
The investigational intervention is KetoneAid MonoEster (D-β-hydroxybutyrate bonded to R-1,3-butanediol), administered orally or enterally at 25 g three times daily (total 75 g/day). The placebo arm receives a taste- and appearance-matched placebo administered on the same schedule. Study drug administration occurs after meals with flexibility to accommodate clinical care.
The primary endpoint is change in NT-proBNP over the treatment period. Secondary outcomes include change in heart failure symptoms using the Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score and change in echocardiographic measures of cardiac function. Exploratory outcomes include glycemic control and insulin requirements, renal function, daily fluid balance adjusted for diuretic dose, and clinical outcomes through 30 days including mortality and days alive and out of hospital. The vanguard design also evaluates feasibility outcomes to inform a subsequent full-scale trial, including consent rate, representation of women, intervention adherence, and follow-up completeness.
Safety monitoring includes daily clinical assessment and laboratory monitoring (including acid-base measures), with predefined adverse events of special interest and stopping rules. An independent Data Safety Monitoring Committee (DSMC) reviews safety data at prespecified enrollment intervals.
- Conditions
- Acute Heart Failure
- Being tested
- Ketone Ester (KetoneAid MonoEster), Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone Ester (KetoneAid MonoEster)Dietary supplement
Participants randomized to the intervention arm will receive KetoneAid MonoEster (D-β-hydroxybutyrate bonded to R-1,3-butanediol) administered orally or enterally at a dose of 25 g three times daily (total 75 g/day) for up to 5 consecutive days (or until discharge or death), in addition to standard of care acute heart failure management.
PlaceboDietary supplement
Participants randomized to the control arm will receive a matching placebo administered orally or enterally three times daily for up to 5 consecutive days (or until discharge or death), in addition to standard of care acute heart failure management.
| Study group | Role | What they receive |
|---|---|---|
| KetoneAid MonoEster | Experimental | Intervention Name: KetoneAid MonoEster Formulation: D-Beta Hydroxybutyrate bonded to R 1,3 Butanediol Dosing: 25 grams, three times per day Administration: Oral or enteral route Duration: 5 consecutive days, or until hospital discharge or death Receives: Dietary Supplement: Ketone Ester (KetoneAid MonoEster) |
| Placebo | Placebo comparator | Matching placebo, also provided by KetoneAid, with similar administration instructions. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in NT-proBNP
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level over the 5-day intervention period comparing ketone ester versus placebo.
Measured: Baseline to Day 5 (or hospital discharge if earlier)
Secondary outcomes (5)
Change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score from baseline to Day 5 comparing treatment groups.
The Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) ranges from 0 to 100, where higher scores indicate fewer heart failure symptoms and better health status, and lower scores indicate more severe symptoms and worse health status.
Measured: Baseline to Day 5 (or hospital discharge if earlier)
Change in Left Ventricular Ejection Fraction (LVEF)
Change in left ventricular ejection fraction from baseline to Day 5 comparing ketone ester versus placebo.
Left ventricular ejection fraction is expressed as a percentage (%), with higher values indicating better systolic function.
Measured: Baseline to Day 5 (or hospital discharge if earlier)
Change in Mitral Inflow E/e' Ratio
Change in mitral inflow E/e' ratio from baseline to Day 5 comparing ketone ester versus placebo.
E/e' ratio is a unitless measure of left ventricular filling pressure. Higher values indicate higher estimated filling pressures and worse diastolic function.
Measured: Baseline to Day 5 (or hospital discharge if earlier)
Change in Stroke Volume
Change in stroke volume from baseline to Day 5 comparing ketone ester versus placebo.
Stroke volume is measured in milliliters (mL). Higher values indicate greater forward blood flow per heartbeat.
Measured: Baseline to Day 5 (or hospital discharge if earlier)
Change in Tricuspid Annular Plane Systolic Excursion (TAPSE)
Change in tricuspid annular plane systolic excursion from baseline to Day 5 comparing ketone ester versus placebo.
TAPSE is measured in millimeters (mm). Higher values indicate better right ventricular systolic function.
Measured: Baseline to Day 5 (or hospital discharge if earlier)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2026
- Study startJan 2027 (estimated)
- Primary completionJul 2027 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Heart FailureStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Study Design: Blinded randomized control trial Patient Population: State 1 - Worsening Heart Failure Development Phase: Vanguard Randomization: 1:1 via automated centralized web-based randomization system within REDCap, stratified by sex using random blocks of 2 or 4
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian VIGOUR Centre, University Hospital Foundation
- Responsible party
- Sponsor
- Investigators
- Fernando G Zampieri, MD, PhD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07434466
- Sponsor's protocol ID
- KETO-01
- Acronym
- KETO-AHF
- Status last verified
- Nov 2026
- First submitted
- 15 Jan 2026
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KETO-AHF: Ketone Ester for Treatment Of Acute Heart Failure: A Vanguard Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07434466
- Acronym / sponsor ID
- KETO-AHF / KETO-01
- Conditions
- Acute Heart Failure
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Canadian VIGOUR Centre, University Hospital Foundation
- Study start
- Jan 2027 (estimated)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 25 Feb 2026 (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.
Ketones have been suggested to have significant physiological effects in patients with heart failure. Potential mechanisms for these effects include energy provision for the failing heart and direct protective effects on other organs. Despite the strong physiological rationale, the acute effects of ketone therapy in patients with acute heart failure (AHF) is unclear. AHF is a major healthcare issue, with in-hospital mortality exceeding 10%. Therefore, we propose a vanguard randomized controlled trial to assess the effects of ketone esters in patients with AHF. Sixty patients hospitalized with AHF will be randomized to receive either 25 grams of ketone esters three times per day or a matching placebo for five days, or until death or hospital discharge. We hypothesize that ketone therapy will improve markers of systemic congestion and heart failure symptoms. Primary endpoint will be changes in NT-proBNP levels during therapy. Secondary endpoints will be KCCQ scores, and hemodynamic profile as assessed by echocardiogram. Exploratory endpoints will clinical outcomes including mortality, need for intensive care unit admission, among others.
Detailed description
KETO-AHF (Ketone Ester for Treatment of Acute Heart Failure) is a single-site, double-blind, randomized, placebo-controlled vanguard clinical trial evaluating the feasibility, safety, and preliminary efficacy of exogenous ketone ester therapy in adults hospitalized with acute heart failure (AHF). The trial is conducted as a domain within the Heart Failure Efficacy and Research Trial (HEART) Platform master protocol framework.
Adults (≥18 years) admitted with a primary diagnosis of acute heart failure will be screened and enrolled within 48 hours of hospital admission. Eligible participants must have dyspnea and clinical evidence of congestion and meet protocol-specified laboratory and clinical criteria, including elevated NT-proBNP and adequate kidney function (eGFR >15 mL/min/1.73m²). Key exclusions include type 1 diabetes mellitus, dialysis dependence, inability to tolerate enteral therapy, and need for advanced mechanical circulatory support or inopressor therapy.
Participants will be randomized 1:1 to receive ketone ester therapy or matching placebo for up to 5 consecutive days (or until hospital discharge or death), in addition to standard-of-care acute heart failure management. Randomization will occur through a centralized web-based system using stratified randomization by sex, and both participants and study staff will remain blinded to allocation.
The investigational intervention is KetoneAid MonoEster (D-β-hydroxybutyrate bonded to R-1,3-butanediol), administered orally or enterally at 25 g three times daily (total 75 g/day). The placebo arm receives a taste- and appearance-matched placebo administered on the same schedule. Study drug administration occurs after meals with flexibility to accommodate clinical care.
The primary endpoint is change in NT-proBNP over the treatment period. Secondary outcomes include change in heart failure symptoms using the Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score and change in echocardiographic measures of cardiac function. Exploratory outcomes include glycemic control and insulin requirements, renal function, daily fluid balance adjusted for diuretic dose, and clinical outcomes through 30 days including mortality and days alive and out of hospital. The vanguard design also evaluates feasibility outcomes to inform a subsequent full-scale trial, including consent rate, representation of women, intervention adherence, and follow-up completeness.
Safety monitoring includes daily clinical assessment and laboratory monitoring (including acid-base measures), with predefined adverse events of special interest and stopping rules. An independent Data Safety Monitoring Committee (DSMC) reviews safety data at prespecified enrollment intervals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Study Design: Blinded randomized control trial Patient Population: State 1 - Worsening Heart Failure Development Phase: Vanguard Randomization: 1:1 via automated centralized web-based randomization system within REDCap, stratified by sex using random blocks of 2 or 4
| Arm | Type | Receives |
|---|---|---|
| KetoneAid MonoEster | Experimental | Dietary Supplement: Ketone Ester (KetoneAid MonoEster)Intervention Name: KetoneAid MonoEster Formulation: D-Beta Hydroxybutyrate bonded to R 1,3 Butanediol Dosing: 25 grams, three times per day Administration: Oral or enteral route Duration: 5 consecutive days, or until hospital discharge or death |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboMatching placebo, also provided by KetoneAid, with similar administration instructions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Ketone Ester (KetoneAid MonoEster)Participants randomized to the intervention arm will receive KetoneAid MonoEster (D-β-hydroxybutyrate bonded to R-1,3-butanediol) administered orally or enterally at a dose of 25 g three times daily (total 75 g/day) for up to 5 consecutive days (or until discharge or death), in addition to standard of care acute heart failure management. | Dietary supplement | KetoneAid MonoEster |
| PlaceboParticipants randomized to the control arm will receive a matching placebo administered orally or enterally three times daily for up to 5 consecutive days (or until discharge or death), in addition to standard of care acute heart failure management. | Dietary supplement | Placebo |
Primary outcome
Change in NT-proBNP
Time frame: Baseline to Day 5 (or hospital discharge if earlier)
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level over the 5-day intervention period comparing ketone ester versus placebo.
5 secondary outcomes
Change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)
Time frame: Baseline to Day 5 (or hospital discharge if earlier)
Change in Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline to Day 5 (or hospital discharge if earlier)
Change in Mitral Inflow E/e' Ratio
Time frame: Baseline to Day 5 (or hospital discharge if earlier)
Change in Stroke Volume
Time frame: Baseline to Day 5 (or hospital discharge if earlier)
Change in Tricuspid Annular Plane Systolic Excursion (TAPSE)
Time frame: Baseline to Day 5 (or hospital discharge if earlier)
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 Nov 2026.
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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.
Fernando G Zampieri, MD, PhD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketone Ester (KetoneAid MonoEster) in people with Acute Heart Failure, run by University of Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: opening soon, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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.
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 Fernando G Zampieri, MD, PhD (587-588-6151, fzampier@ualberta.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in NT-proBNP (time frame: Baseline to Day 5 (or hospital discharge if earlier)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Nov 2026.