Treatment With the Ketone Body 3-hydroxybutyrate in Patients With Cardiogenic Shock (KETO-SHOCK1)

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.

Study Overview

• Status: Completed
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Dietary supplement: KetoneAid Ketone Ester; Dietary supplement: Maltodextrin

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Midtjylland
    • Aarhus, Midtjylland, Denmark, 8200
      • Aarhus University Hospital

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:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3-Hydroxybutyrate treatment; KetoneAid Ketone Ester 0,5g/kg (max. 50g) bolus	Dietary supplement: KetoneAid Ketone Ester; Commercially available ketone supplement
Placebo Comparator: Placebo Treatment; Maltodextrin-base isocaloric placebo	Dietary supplement: Maltodextrin; Commercially available maltodextrin supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Output (L/min) area under curve	Right Heart Catheterization (by thermodilution)	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac output (L/min)	Right Heart Catheterization (by thermodilution)	1 hour
Left Ventricular Filling Pressure (mmHg) area under curve	Right Heart Catheterization	3 hours
Cardiac Power Output (W) area under curve	mean arterial pressure x cardiac output/451	3 hours
Mixed Venous Saturation (%) area under curve	Right Heart Catheterization	3 hours
Left Ventricular Ejection Fraction (%) area under curve	Echocardiography	3 hours
Hourly urinary output (mL/hour) area under curve		3 hours
Renal Perfusion (mL/min)	Renal doppler ultrasound	1 hours
Arterial Lactate (mmol/L) area under curve	Arterial blood gas measurements	3 hours
Cumulative doses of inotropes and vasopressors during the 3 hour studyperiod		3 hours
Cerebral Perfusion area under curve	Near-infrared spectroscopy	3 hours
Peripheral Perfusion area under curve	Near-infrared spectroscopy	3 hours

Collaborators and Investigators

• Sponsor: University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): May 17, 2022
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: November 18, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 24, 2020

Study Record Updates

• Last Update Posted (Actual): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Ketone bodies; β-hydroxybutyrate
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic
• Other Study ID Numbers: KETO-SHOCK 1-10-72-209-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No