Hemodynamic Effects of Ketone Esters in Patients With Sepsis Induced Cardiomyopathy

NCT06952140 | Not Yet Recruiting

• 1 other identifier: KetoSIC
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

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. .

Conditions

Sepsis Induced Cardiomyopathy

Keywords

Sepsis induced cardiomyopathy; Sepsis; Hemodynamics; Ketone ester; Ketones; Echocardiography; Randomized controlled trial; Cross-over trial; Cardiovascular

Outcome Measures

Primary Outcomes (1)

• Global longitudinal strain

  Echocardiographic measure obtained from transthoracic echocardiography

  From intervention to 3 hours after intervention (this is assessed for both treatment arms)

Secondary Outcomes (7)

• Left ventricular ejection fraction

  From intervention to 3 hours after intervention (this is assessed for both treatment arms)

• Mean arterial pressure

  From intervention to 3 hours after intervention (this is assessed for both treatment arms)

• Cardiac output

  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)

Study Arms (2)

Ketone ester followed by placebo

EXPERIMENTAL

Dietary Supplement: Ketone ester; Dietary Supplement: Placebo

Placebo followed by ketone ester

EXPERIMENTAL

Dietary Supplement: Ketone ester; Dietary Supplement: Placebo

Interventions

Ketone ester DIETARY_SUPPLEMENT

Ketone ester: 3-hydroxybutyrate as enteral bolus (500 mg/kg)

Ketone ester followed by placebo; Placebo followed by ketone ester

Placebo DIETARY_SUPPLEMENT

Maltodextrin (isovolumic and isocaloric placebo) as enteral bolus

Ketone ester followed by placebo; Placebo followed by ketone ester

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Tor Biering-Sørensen: lead

MeSH Terms

Conditions

Sepsis; Ketosis

Interventions

formic acid 4-(3-oxobutyl)phenyl ester

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Tor Biering-Sørensen, MD, MPH, MSc, PhD

  Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katrine F Bernholm, MD

CONTACT

0045 24909488; katrine.feldballe.bernholm@regionh.dk

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: SPONSOR INVESTIGATOR
• PI Title: Professor, MD, MSc, MPH, PhD

Model Details: As this is a cross-over trial participants will receive both active treatment and placebo. Participants will be randomized 1:1 to receive A) active treatment followed by placebo or B) placebo followed by active treatment.

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: April 30, 2025
• Study Start: March 10, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03