Ignite Creation Date:
2026-03-26 @ 3:15 PM
Ignite Modification Date:
2026-03-26 @ 3:15 PM
Study NCT ID:
NCT07434466
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-02-25
First Post:
2026-01-15
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Ketone Ester for Treatment Of Acute Heart Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Blinding: Double-blind using placebo matching taste and appearance of ketone esters'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': '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'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 60}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-03', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2028-03', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-19', 'studyFirstSubmitDate': '2026-01-15', 'studyFirstSubmitQcDate': '2026-02-19', 'lastUpdatePostDateStruct': {'date': '2026-02-25', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-25', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-03', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Change in serum creatinine', 'timeFrame': 'Baseline to Day 5 (or discharge if earlier)', 'description': 'Change in renal function measured by serum creatinine over the intervention period.'}, {'measure': 'Insulin requirements', 'timeFrame': 'Day 1 through Day 5 (or discharge if earlier)', 'description': 'Total insulin administered during the inpatient intervention period.'}, {'measure': 'Glycemic control', 'timeFrame': 'Day 1 through Day 5 (or discharge if earlier)', 'description': 'Daily blood glucose measurements during the intervention period.'}, {'measure': 'Days Alive and Out of Hospital', 'timeFrame': '30 days', 'description': 'Number of days alive and out of hospital through Day 30 after randomization.'}, {'measure': 'All-cause mortality', 'timeFrame': '30 days', 'description': 'All-cause mortality through Day 30 after randomization.'}, {'measure': 'Major Adverse Kidney Events', 'timeFrame': '30 days', 'description': 'Composite kidney outcome through Day 30, including death, new renal replacement therapy, or persistent renal dysfunction.'}, {'measure': 'Daily Net Fluid Balance Adjusted for Loop Diuretic Dose', 'timeFrame': 'Day 1 through Day 5 (or hospital discharge if earlier)', 'description': 'Daily net fluid balance during the inpatient intervention period (Day 1 through Day 5 or hospital discharge if earlier), adjusted for total loop diuretic dose administered.\n\nNet fluid balance will be calculated as total fluid intake minus total fluid output and normalized to loop diuretic dose received during the same period.'}], 'primaryOutcomes': [{'measure': 'Change in NT-proBNP', 'timeFrame': 'Baseline to Day 5 (or hospital discharge if earlier)', 'description': 'Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level over the 5-day intervention period comparing ketone ester versus placebo.'}], 'secondaryOutcomes': [{'measure': 'Change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)', 'timeFrame': 'Baseline to Day 5 (or hospital discharge if earlier)', 'description': 'Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score from baseline to Day 5 comparing treatment groups.\n\nThe 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.'}, {'measure': 'Change in Left Ventricular Ejection Fraction (LVEF)', 'timeFrame': 'Baseline to Day 5 (or hospital discharge if earlier)', 'description': 'Change in left ventricular ejection fraction from baseline to Day 5 comparing ketone ester versus placebo.\n\nLeft ventricular ejection fraction is expressed as a percentage (%), with higher values indicating better systolic function.'}, {'measure': "Change in Mitral Inflow E/e' Ratio", 'timeFrame': 'Baseline to Day 5 (or hospital discharge if earlier)', 'description': "Change in mitral inflow E/e' ratio from baseline to Day 5 comparing ketone ester versus placebo.\n\nE/e' ratio is a unitless measure of left ventricular filling pressure. Higher values indicate higher estimated filling pressures and worse diastolic function."}, {'measure': 'Change in Stroke Volume', 'timeFrame': 'Baseline to Day 5 (or hospital discharge if earlier)', 'description': 'Change in stroke volume from baseline to Day 5 comparing ketone ester versus placebo.\n\nStroke volume is measured in milliliters (mL). Higher values indicate greater forward blood flow per heartbeat.'}, {'measure': 'Change in Tricuspid Annular Plane Systolic Excursion (TAPSE)', 'timeFrame': 'Baseline to Day 5 (or hospital discharge if earlier)', 'description': 'Change in tricuspid annular plane systolic excursion from baseline to Day 5 comparing ketone ester versus placebo.\n\nTAPSE is measured in millimeters (mm). Higher values indicate better right ventricular systolic function.'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Acute Heart Failure']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nAdults (≥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.\n\nParticipants 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.\n\nThe 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.\n\nThe 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.\n\nSafety 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Domain-Specific Inclusion Criteria:\n\n1. 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\\]\n2. Admitted to the hospital for less than 48 hours\n3. Estimated glomerular filtration rate above 15 mL/min/1.73m²\n4. NT-proBNP ≥ 1000 pg/ml\n\nDomain-Specific Exclusion Criteria:\n\n1. Type 1 diabetes mellitus\n2. Patients on mechanical circulatory support\n3. Patients on more than one inotrope or on inopressors\n4. Patients on dialysis\n5. Patients with non-functioning enteral tracks'}, 'identificationModule': {'nctId': 'NCT07434466', 'acronym': 'KETO-AHF', 'briefTitle': 'Ketone Ester for Treatment Of Acute Heart Failure', 'organization': {'class': 'OTHER', 'fullName': 'University of Alberta'}, 'officialTitle': 'KETO-AHF: Ketone Ester for Treatment Of Acute Heart Failure: A Vanguard Randomized Controlled Trial', 'orgStudyIdInfo': {'id': 'KETO-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'KetoneAid MonoEster', 'description': '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', 'interventionNames': ['Dietary Supplement: Ketone Ester (KetoneAid MonoEster)']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Matching placebo, also provided by KetoneAid, with similar administration instructions.', 'interventionNames': ['Dietary Supplement: Placebo']}], 'interventions': [{'name': 'Ketone Ester (KetoneAid MonoEster)', 'type': 'DIETARY_SUPPLEMENT', 'description': '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.', 'armGroupLabels': ['KetoneAid MonoEster']}, {'name': 'Placebo', 'type': 'DIETARY_SUPPLEMENT', 'description': '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.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Edmonton', 'state': 'Alberta', 'country': 'Canada', 'facility': 'University of Alberta', 'geoPoint': {'lat': 53.55014, 'lon': -113.46871}}], 'centralContacts': [{'name': 'Fernando G Zampieri, MD, PhD', 'role': 'CONTACT', 'email': 'fzampier@ualberta.ca', 'phone': '587-588-6151'}, {'name': 'Justin Ezekowitz, MD', 'role': 'CONTACT', 'email': 'jae2@ualberta.ca', 'phone': '780-492-0712'}], 'overallOfficials': [{'name': 'Fernando G Zampieri, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Alberta'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Alberta', 'class': 'OTHER'}, 'collaborators': [{'name': 'Canadian VIGOUR Centre', 'class': 'OTHER'}, {'name': 'University Hospital Foundation', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}