Treatment With the Ketone Body 3-hydroxybutyrate in Patients With Cardiogenic Shock

NCT04642768 | Completed DMC

• 1 other identifier: KETO-SHOCK 1-10-72-209-20
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Background Cardiogenic shock is a life-threatening state of acute heart failure with severely depressed blood pressure and organ perfusion. The 30-day mortality is reported as high as 50%. To date, no randomized trial has documented a survival benefit of any medical treatment in this patient group. In a first-in-man study the investigators have recently discovered that treatment with ketone bodies increases cardiac output by 2 liters per minute. Objective The present study aims to examine the direct effects of ketone body supplements on the heart function in patients hospitalized with cardiogenic shock. Also, the aim is to determine the relative need for medical circulatory support following ketone body supplement. Design A randomized double-blind cross-over study of the hemodynamic effect of enteral ketone ester versus placebo in 12 patients with cardiogenic shock Methods Right heart catheterization will be installed to monitor cardiac pressures and output. The investigators will observe heart function with transthoracic echocardiography. Blood- and urine samples will be analyzed for electrolytes, energy substrates and vasoactive substances. Organ perfusion is to be examined by renal ultrasonography and near-infrared spectroscopy for measuring cerebral and peripheral circulation. Perspectives This investigation may grant essential knowledge on ketosis in cardiogenic shock. This may lead to larger clinical trials, and hopefully a new and better treatment for patients with cardiogenic shock.

Conditions

Cardiogenic Shock

Keywords

Ketone bodies; β-hydroxybutyrate

Outcome Measures

Primary Outcomes (1)

• Cardiac Output (L/min) area under curve

  Right Heart Catheterization (by thermodilution)

  3 hours

Secondary Outcomes (11)

• Cardiac output (L/min)

  1 hour

• Left Ventricular Filling Pressure (mmHg) area under curve

  3 hours

• Cardiac Power Output (W) area under curve

  3 hours

• Mixed Venous Saturation (%) area under curve

  3 hours

• Left Ventricular Ejection Fraction (%) area under curve

  3 hours

Study Arms (2)

3-Hydroxybutyrate treatment

EXPERIMENTAL

KetoneAid Ketone Ester 0,5g/kg (max. 50g) bolus

Dietary Supplement: KetoneAid Ketone Ester

Placebo Treatment

PLACEBO COMPARATOR

Maltodextrin-base isocaloric placebo

Dietary Supplement: Maltodextrin

Interventions

KetoneAid Ketone Ester DIETARY_SUPPLEMENT

Commercially available ketone supplement

3-Hydroxybutyrate treatment

Maltodextrin DIETARY_SUPPLEMENT

Commercially available maltodextrin supplement

Placebo Treatment

Eligibility Criteria

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

You may qualify if:

• Ongoing treatment with inotropes and/or vasopressors because of cardiogenic shock as judged by the clinicians
• Patients are required at some point in time to have had \> 1 of the following: systolic blood pressure \< 90 mmHg; arterial blood lactate ≥ 2.5mmol/l; organ hypoperfusion (e.g. urinary output \< 0.5 ml/kg/hour or SvO2 \<55% with normal PaO2 and Hgb)
• LVEF \< 40%
• Age ≥ 18 years

You may not qualify if:

• Other primary causes of shock (hypovolemia, hemorrhage, severe infection or sepsis, pulmonary embolism or anaphylaxis),
• Shock due to mechanical complication to myocardial infarction (papillary muscle rupture, rupture of the ventricular septum or rupture of free wall)
• INTERMACS level 1 or 2 \[18\] with unstable or sliding hemodynamics on inotropes/vasopressors
• Use of or probable need for mechanic circulatory support (e.g. left ventricular assistant device, IMPELLA, extracorporeal membrane oxygenation)
• Recent post-cardiotomy cardiogenic shock (defined as thoracic surgery with the last 3 days)
• Inability to position a nasogastric tube
• Severe gastroparesis or abdominal distension

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, Central Jutland, 8200, Denmark

Location

Related Publications (1)

• Berg-Hansen K, Christensen KH, Gopalasingam N, Nielsen R, Eiskjaer H, Moller N, Birkelund T, Christensen S, Wiggers H. Beneficial Effects of Ketone Ester in Patients With Cardiogenic Shock: A Randomized, Controlled, Double-Blind Trial. JACC Heart Fail. 2023 Oct;11(10):1337-1347. doi: 10.1016/j.jchf.2023.05.029. Epub 2023 Jul 12.

  PMID: 37452805 DERIVED

MeSH Terms

Conditions

Shock, Cardiogenic

Interventions

maltodextrin

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 24, 2020
• Study Start: January 1, 2021
• Primary Completion: May 17, 2022
• Study Completion: May 17, 2022
• Last Updated: May 20, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)