Exogenous Ketones for Acutely Decompensated HEart Failure

Hemodynamic Instability Clinical Trial

— KADHEF  

Official title:

Exogenous Ketones for Acutely Decompensated Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04698005
• Other study ID #: A-20-28
• Status: Recruiting
• Phase: Phase 3
• Start date: December 2, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: January 2021
• Source: Institute for Clinical and Experimental Medicine
• Contact: Marek Sramko, MD, PhD
• Phone: +420776246127
• Email: marek.sramko[@]ikem.cz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Heart Failure
• Cardiac Output, Low
• Heart Failure
• Hemodynamic Instability
• Ketosis
• Low Cardiac Output Syndrome

Intervention

Dietary Supplement:
• 25g Ketone monoester without added salts
oral supplementation of ketone monoester

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

Locations

Country	Name	City	State
Czechia	Institute for Clinical and Experimental Medicine (IKEM)	Prague

Sponsors (1)

Lead Sponsor	Collaborator
Institute for Clinical and Experimental Medicine

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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