Ketone Ester for Treatment Of Acute Heart Failure

NCT07434466 | Not Yet Recruiting DMC

• 1 other identifier: KETO-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Acute Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Day 5 (or hospital discharge if earlier)

Secondary Outcomes (5)

• Change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)

  Baseline to Day 5 (or hospital discharge if earlier)

• Change in Left Ventricular Ejection Fraction (LVEF)

  Baseline to Day 5 (or hospital discharge if earlier)

• Change in Mitral Inflow E/e' Ratio

  Baseline to Day 5 (or hospital discharge if earlier)

• Change in Stroke Volume

  Baseline to Day 5 (or hospital discharge if earlier)

• Change in Tricuspid Annular Plane Systolic Excursion (TAPSE)

  Baseline to Day 5 (or hospital discharge if earlier)

Other Outcomes (7)

• Change in serum creatinine

  Baseline to Day 5 (or discharge if earlier)

• Insulin requirements

  Day 1 through Day 5 (or discharge if earlier)

• Glycemic control

  Day 1 through Day 5 (or discharge if earlier)

Study Arms (2)

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

Dietary Supplement: Ketone Ester (KetoneAid MonoEster)

Placebo

PLACEBO COMPARATOR

Matching placebo, also provided by KetoneAid, with similar administration instructions.

Dietary Supplement: Placebo

Interventions

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.

KetoneAid MonoEster

Placebo DIETARY_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.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alberta: lead
• Canadian VIGOUR Centre: collaborator
• University Hospital Foundation: collaborator

Study Sites (1)

University of Alberta

Edmonton, Alberta, Canada

Location

Study Officials

• Fernando G Zampieri, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fernando G Zampieri, MD, PhD

CONTACT

587-588-6151; fzampier@ualberta.ca

Justin Ezekowitz, MD

CONTACT

780-492-0712; jae2@ualberta.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding: Double-blind using placebo matching taste and appearance of ketone esters
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 15, 2026
• First Posted: February 25, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

CA (1)