Exogenous Ketones for Acutely Decompensated HEart Failure

NCT ID: NCT04698005

Last Updated: 2021-01-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-02
• Study Completion Date: 2021-12-31

Brief Summary

This study will evaluate whether supplementation of exogenous ketones in patients with severe left ventricular dysfunction and acutely decompensated heart failure requiring inotropic therapy would improve the patient's hemodynamics and symptoms.

Detailed Description

The study will include patients with acutely decompensated chronic heart failure requiring inotropic therapy for the syndrome of low cardiac output. While being on the inotropic therapy, the patients will be randomized to oral supplementation of exogenous ketones vs. placebo, which will be repeatedly administered over 9 hours. The patients will undergo continuous invasive hemodynamic monitoring by pulmonary artery catheter, repeated laboratory assessment, and repeated assessment of the severity of symptoms for 24 hours.

Exogenous ketones will be administered orally using monoester 3-OHB concentrate without added salts (25g 3-OHB in 65ml H.V.M.N Ketone Ester, H.V.M.N, USA or equivalent). The drink will be administered over 10 mins every 3 hours, 3 times in a row (hour 0, 3, 6).

All patients with K<3.7 mmol/l will receive a continuous infusion of 7.5% potassium until reach target K levels of 4.0-4.9 mmol /l. Glycemia will be controlled as needed by insulin and dextrose to maintain glucose concentration of 4 - 12 mmol/l

All patients will receive standard treatment of acute heart failure, including intravenous diuretics and inotropic therapy. The recommended inotropic therapy will include milrinone 0.5 ug/kg/min, levosimendan 0.1 ug/kg/min up to 25mg without initial bolus, or dobutamine 0.5 ug/kg/min in patients without chronic therapy with beta-blockers.

The severity of symptoms will be self-reported by the patient using 1-10 visual analog scale.

Workflow:

• Hemodynamic assessment, assessment of ketones concentration: 1-3h before randomization, 0-9h hourly, 16-24h (next morning)
• Biochemical assessment (renal function, liver enzymes, BNP, hs-TnT) 0h, 9h, 16-24h
• Assessment of symptoms and Scv02: 0h, 1h, 3h, 9h, 16-24h

Statistical methods:

Each study arm will include 12 patients. The study size was estimated to have power of (1 - beta) of 0.8 and alpha of 5% for between-group comparison of changes in cardiac index and stroke volume index by ANOVA and for comparison of the changes in cardiac index and stroke volume index by paired t-tests.

Conditions

Acute Heart Failure; Low Cardiac Output Syndrome; Hemodynamic Instability; Ketosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Supplementation of exogenous ketones

Exogeneous ketones will be administered orally using monoester 3-OHB concentrate without added salts (25g 3-OHB in 65ml H.V.M.N Ketone Ester, H.V.M.N, USA or equivalent). The drink will be administered over 10 mins every 3 hours, 3 times in a row.

Group Type: EXPERIMENTAL

25g Ketone monoester without added salts

Intervention Type: DIETARY_SUPPLEMENT

oral supplementation of ketone monoester

Control group

The patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

The patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml)

Interventions

25g Ketone monoester without added salts

oral supplementation of ketone monoester

Intervention Type: DIETARY_SUPPLEMENT

Placebo

The patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml)

Intervention Type: OTHER

Other Intervention Names

25g 3-OHB in 65ml, H.V.M.N Ketone Ester, H.V.M.N, USA or equivalent

Eligibility Criteria

Inclusion Criteria

• Chronic heart failure due ischemic or nonischemic cardiomyopathy
• Acute decompensation of heart failure with the need of inotropes
• Achievement of relative stabilization on inotropes (INTERMACS class >2)
• Left ventricular ejection fraction <= 35%
• Age >18 years

Exclusion Criteria

• Deteriorating cardiogenic shock with likely need of mechanical circulatory support in the subsequent 48 hours
• Chronic kidney disease grade 4 or 5
• Diabetic ketoacidosis (3-OHB >2mmol/l at baseline)
• Hemodynamic severe arrhythmias
• Acute heart failure due to transient triggers (acute coronary syndrome, atrial fibrillation, infection etc..)
• Contraindications to invasive hemodynamic monitoring

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute for Clinical and Experimental Medicine

OTHER_GOV

Sponsor Role: lead

Responsible Party

Marek Sramko

Head of the Department of Acute Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Institute for Clinical and Experimental Medicine (IKEM)

Prague, , Czechia

Site Status: RECRUITING

Countries

Czechia

Central Contacts

Marek Sramko, MD, PhD

Role: CONTACT

marek.sramko@ikem.cz

+420776246127

Facility Contacts

Marek Sramko, MD, PhD

Role: primary

marek.sramko@ikem.cz

+420731682681

Other Identifiers

A-20-28

Identifier Type: -

Identifier Source: org_study_id