Hemodynamic Effects of Ketone Esters in Patients With Sepsis Induced Cardiomyopathy (KetoSIC)

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is associated with a high mortality rate in the ICU. Sepsis induced cardiomyopathy (SICM) is a multi-factorial process that appears in approximately 50% of patients with sepsis/septic shock and is associated with increased mortality. It is suggested that ketone bodies are more efficient substrates of energy metabolism than glucose, with a lower oxygen consumption per ATP-molecule produced and that the failing human heart increases the capacity to metabolize ketones. Previous studies have found acute beneficial hemodynamic effects of ketone esters in patients with chronic heart failure and cardiogenic shock, respectively. Improved hemodynamics and reduced systemic oxygen consumption as an effect of ketone esters might be of great benefit in patients admitted to the ICU. Thus, the investigators aim to investigate the hemodynamic effects of ketone esters in patients with sepsis induced cardiomyopathy in this randomized, placebo-controlled, double-blinded, cross-over, acute intervention study. .

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis Induced Cardiomyopathy
• Intervention / Treatment: Dietary supplement: Ketone ester; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katrine F Bernholm, MD; Phone Number: 0045 24909488; Email: katrine.feldballe.bernholm@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥ 18 years of age admitted to the the intensive care unit (ICU)
• LVEF < 50% determined by a screening echocardiography and analysed according to the Simpson biplane method
• Ability for study personnel to perform transthoracic echocardiography
• Suspected or documented infection (suspected infection is defined as ongoing antibiotic treatment and/or body fluid culture sampling performed within 72 hours before screening)

Exclusion Criteria:

• Diagnosis of heart failure with reduced ejection fraction prior to ICU admission according to health records
• Surgical cause of ICU admission
• For patients in shock: Other primary causes of shock than sepsis (i.e. hypovolemia, haemorrhage, cardiogenic etiology, pulmonary embolism, anaphylaxis)
• Blood pH < 7.20
• Severe gastroparesis
• Inability to position a nasogastric tube

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: Ketone ester followed by placebo	Dietary supplement: Ketone ester; Ketone ester: 3-hydroxybutyrate as enteral bolus (500 mg/kg); Dietary supplement: Placebo; Maltodextrin (isovolumic and isocaloric placebo) as enteral bolus
Experimental: Placebo followed by ketone ester	Dietary supplement: Ketone ester; Ketone ester: 3-hydroxybutyrate as enteral bolus (500 mg/kg); Dietary supplement: Placebo; Maltodextrin (isovolumic and isocaloric placebo) as enteral bolus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global longitudinal strain	Echocardiographic measure obtained from transthoracic echocardiography	From intervention to 3 hours after intervention (this is assessed for both treatment arms)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular ejection fraction	Echocardiographic measure obtained from transthoracic echocardiography	From intervention to 3 hours after intervention (this is assessed for both treatment arms)
Mean arterial pressure	Obtained from invasive blood pressure measurement (arterial line)	From intervention to 3 hours after intervention (this is assessed for both treatment arms)
Cardiac output	Obtained from transthoracic echocardiography	From intervention to 3 hours after intervention (this is assessed for both treatment arms)
Peripheral blood oxygen saturation		From intervention to 3 hours after intervention (this is assessed for both treatment arms)
Arterial blood pH		From intervention to 3 hours after intervention (this is assessed for both treatment arms)
Arterial blood lactate		From intervention to 3 hours after intervention (this is assessed for both treatment arms)
Accumulated norepinephrine		From intervention to 3 hours after intervention (this is assessed for both treatment arms)

Collaborators and Investigators

• Sponsor: Tor Biering-Sørensen
• Investigators: Principal Investigator: Tor Biering-Sørensen, MD, MPH, MSc, PhD, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Study record dates

Study Major Dates

• Study Start (Estimated): March 10, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 23, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 30, 2025

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Cardiovascular; Sepsis; Echocardiography; Hemodynamics; Ketones; Ketone ester; Cross-over trial; Sepsis induced cardiomyopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Acid-Base Imbalance; Acidosis; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Sepsis; Ketosis; formic acid 4-(3-oxobutyl)phenyl ester
• Other Study ID Numbers: KetoSIC

Drug and device information, study documents

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