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

Study Overview
=================
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.

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

Conditions
-----------------
Cardiogenic Shock

Intervention / Treatment
-----------------
* Dietary Supplement: KetoneAid Ketone Ester
* Dietary Supplement: Maltodextrin


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ketone bodies, β-hydroxybutyrate