Clinical trial NCT04642768: Treatment With the Ketone Body 3-hydroxybutyrate in Patients With Cardiogenic Shock
Official title: Treatment With the Ketone Body 3-hydroxybutyrate in Patients With Cardiogenic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiogenic Shock
Keywords: Ketone bodies
β-hydroxybutyrate
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2020-11-24
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Cardiac Output (L/min) area under curve
timeFrame: 3 hours
Secondary outcomes:
measure: Cardiac output (L/min)
timeFrame: 1 hour
measure: Left Ventricular Filling Pressure (mmHg) area under curve
timeFrame: 3 hours
measure: Cardiac Power Output (W) area under curve
timeFrame: 3 hours
measure: Mixed Venous Saturation (%) area under curve
timeFrame: 3 hours
measure: Left Ventricular Ejection Fraction (%) area under curve
timeFrame: 3 hours
measure: Hourly urinary output (mL/hour) area under curve
timeFrame: 3 hours
measure: Renal Perfusion (mL/min)
timeFrame: 1 hours
measure: Arterial Lactate (mmol/L) area under curve
timeFrame: 3 hours
measure: Cumulative doses of inotropes and vasopressors during the 3 hour studyperiod
timeFrame: 3 hours
measure: Cerebral Perfusion area under curve
timeFrame: 3 hours
measure: Peripheral Perfusion area under curve
timeFrame: 3 hours
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
state: Midtjylland
Study officials:
References: