Exogenous Ketones for Acutely Decompensated HEart Failure (KADHEF)

Exogenous Ketones for Acutely Decompensated Heart Failure

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.

Study Overview

• Status: Recruiting
• Conditions: Ketosis; Acute Heart Failure; Hemodynamic Instability; Low Cardiac Output Syndrome
• Intervention / Treatment: Dietary supplement: 25g Ketone monoester without added salts; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 14059
    • Recruiting
    • Institute for Clinical and Experimental Medicine (IKEM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Dietary supplement: 25g Ketone monoester without added salts; oral supplementation of ketone monoester; Other Names: 25g 3-OHB in 65ml, H.V.M.N Ketone Ester, H.V.M.N, USA or equivalent
Placebo Comparator: Control group; The patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml)	Other: Placebo; The patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum change of stroke volume index	Maximum change of stroke volume index (ml/m2) between baseline and hour 1 - 3	Maximum value of stroke volume index measured between hour 1 - 3 of the study protocol at 15-minute intervals
Maximum change of cardiac index	Maximum change of cardiac index (L/m2) between baseline and hour 1 - 3	Maximum value of cardiac index measured between hour 1 - 3 of the study protocol at 15-minute intervals
Change of mean stroke volume index	Difference between baseline stroke volume index and mean stroke volume index (ml/m2) during the study protocol	Mean value of stroke volume index measured every 15 minutes during 9 hours of the study protocol
Change of mean cardiac index	Difference between baseline cardiac index (L/m2) and mean cardiac index during the study protocol	Mean value of cardiac index measured every 15 minutes during 9 hours of the study protocol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in patient/symptoms	Change in patient-referred symptoms by visual-analog scale (1=unbearable dyspnea, 10=no symptoms)	Symptoms scored at hours 0, 1, 10, 24 and expressed as an area under the curve

Collaborators and Investigators

• Sponsor: Institute for Clinical and Experimental Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: January 5, 2021
• First Posted (Actual): January 6, 2021

Study Record Updates

• Last Update Posted (Actual): January 6, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Cardiac Output, Low
• Other Study ID Numbers: A-20-28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes