Ketamine Sedation As Neuroprotective Agent Following Out-of-hospital Cardiac Arrest (KETOHCA)

KETamine Sedation As Neuroprotective Agent Following Out-of-hospital Cardiac Arrest (OHCA) - the KETOHCA Trial

OHCA is a critical medical emergency with significant mortality and morbidity primarily due to hypoxic-ischemic brain injury (HIBI). Despite advances in resuscitation techniques, the neurological outcomes for survivors remain poor. Current post-resuscitation practices lack specific neuroprotective strategies. Ketamine, an N-Methyl-D-Aspartate (NMDA) receptor antagonist, has shown potential neuroprotective properties in preclinical and clinical studies due to its ability to inhibit excitotoxicity and reduce neuronal apoptosis. This trial hypothesizes that ketamine, when used for sedation in OHCA patients, may offer superior neuroprotective benefits compared to the commonly used sedative propofol. By comparing the effects of ketamine and propofol on neuronal damage markers and long-term neurological outcomes, this study aims to identify a potentially effective intervention to improve the prognosis of OHCA patients.

Study Overview

• Status: Recruiting
• Conditions: Out-of-hospital Cardiac Arrest (OHCA)
• Intervention / Treatment: Drug: esketamine hydrochloride; Drug: propofol

• Study Type: Interventional
• Enrollment (Estimated): 282
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Salma Charabi, MD; Phone Number: 35450572; Email: salma.charabi@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Department of Cardiology, Rigshospitalet
    • Contact: Laust R Obling, MD; Phone Number: +4520404577; Email: laust.obling.01@regionh.dk
    • Contact: Laust R Obling, MD
    • Contact: Salma Charabi, MD
  • Odense C, Denmark, 5000
    • Not yet recruiting
    • Odense University Hospital
    • Contact: Henrik Schmidt, MD; Phone Number: +4529647253; Email: henrik.schmidt@rsyd.dk
    • Contact: Henrik Schmidt, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults (age ≥18 years) AND
• resuscitated OHCA of presumed cardiac cause with a shockable first recorded heart rhythm AND
• mean arterial pressure (MAP) >40 mmHg AND
• a decision to perform prehospital intubation.

Exclusion Criteria:

• Advanced life support termination-of-resuscitation (TOR) criteria met
• Systolic blood pressure >190 mmHg
• Known allergy to ketamine or propofol
• Chronic diseases making 180-day survival unlikely
• Body temperature <30° C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-ketamin; Intravenous or intraosseous bolus administration at a minimum of 0.5 mg/kg of esketamine	Drug: esketamine hydrochloride; Prehospital intravenous or intraosseous bolus administration at a minimum of 0.5 mg/kg of esketamine
Active Comparator: Propofol; Prehospital intravenous or intraosseous bolus administration of a minimum dose of 0.25 mg/kg propofol	Drug: propofol; Prehospital intravenous or intraosseous bolus administration at a minimum dose of 0.25 mg/kg propofol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuron-specific enolase (NSE) measured 48 hours after OHCA	To determine the neuroprotective efficacy of ketamine compared with propofol administered as part of sedation for intubation after initial resuscitation from OHCA	48 hours after OHCA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death from any cause	Death from any cause 180 days after cardiac arrest	180 days after cardiac arrest
Neurological outcome: modified Rankin Score (mRS)	Neurological outcome by and modified Rankin Score (mRS). Meassured from 0 to 6, where 0 is no symptoms.	At 2 weeks (at discharge)
Neurological outcome: Cerebral Performance Categories (CPC)	Neurological outcome by Cerebral Performance Categories (CPC) meassured fra 1-5 (a score of 1 is normal/good cerebral function).	At 2 weeks (at discharge)
Neurological outcome: modified Rankin Score (mRS)	Neurological outcome by and modified Rankin Score (mRS). Meassured from 0 to 6, where 0 is no symptoms.	At 180 days after OHCA.
Neurological outcome: modified Rankin Score (mRS)	Neurological outcome by and modified Rankin Score (mRS). Meassured from 0 to 6, where 0 is no symptoms.	At 240 days after OHCA.
Neurological outcome: Cerebral Performance Categories (CPC)	Neurological outcome by Cerebral Performance Categories (CPC) meassured fra 1-5 (a score of 1 is normal/good cerebral function).	At 180 days after OHCA.
Neurological outcome: Cerebral Performance Categories (CPC)	Neurological outcome by Cerebral Performance Categories (CPC) meassured fra 1-5 (a score of 1 is normal/good cerebral function).	At 240 days after OHCA.

Collaborators and Investigators

• Sponsor: Christian Hassager

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: December 6, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Hypnotics and Sedatives; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Antidepressive Agents; Esketamine; Propofol
• Other Study ID Numbers: 2024-515987-29-00 (Ctis)

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
• product manufactured in and exported from the U.S.: No