Ketamine for Sedation in Severe Traumatic Brain Injury (Ketamine)

July 10, 2025 updated by: Henry M. Jackson Foundation for the Advancement of Military Medicine
This protocol is for an open-label randomized trial evaluating the safety of using ketamine in combination with propofol for sedation versus the standard of care analgosedation in patients admitted to the intensive care unit with severe traumatic brain injury.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

Patients meeting eligibility criteria and consent having been obtained by LAR will undergo randomization to either the ketamine with propofol intervention arm or the standard of care control arm.

Patients enrolled in the intervention arm will receive propofol at a rate of 300 mcg/kg/hr (5 mcg/kg/min) with the addition of ketamine at a rate of 1000-5000 mcg/kg/hr (16.67 - 83.33 mcg/kg/min) (using weight at time of admission) with an additional 2 mg/kg (2000 mcg/kg) bolus of ketamine, for sustained ICP elevations over 22mHg for greater than 5 minutes not attributed to other causes (coughing etc.). In the control arm, patients will receive their institutional analgosedation protocol. The sedation protocols will be continued until removal of intracranial pressure monitoring.

This study will take place during the participant's hospital care. The clinical team will administer treatment using standard practices, including all safety precautions available. Side effects will be monitored closely and may decide to discontinue the subject's participation in the study should the subject's health or safety are at risk.

The research team will performed one outpatient follow-up after study intervention ends.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Fort Sam Houston, Texas, United States, 78234
        • Brooke Army Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults 18-65 years of age
  • Severe traumatic brain injury (TBI), with a Glasgow Coma Scale (GCS) ≤ 8, requiring intracranial monitoring
  • Placement of intracranial pressure monitor
  • Receiving treatment in an intensive care unit (ICU)

Exclusion Criteria:

  • Significant cardiovascular disease with recent coronary intervention
  • Pregnancy
  • Prisoners
  • Known allergy to ketamine or propofol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ketamine with propofol
Propofol at a rate of 300 mcg/kg/hr (5 mcg/kg/min) with the addition of ketamine at a rate of 1000-5000 mcg/kg/hr (16.67 - 83.33 mcg/kg/min) (using weight at time of admission) with an additional 2 mg/kg (2000 mcg/kg) bolus of ketamine
Drug: Ketamine with propofol
Propofol at a rate of 300 mcg/kg/hr (5 mcg/kg/min) with the addition of ketamine at a rate of 1000-5000 mcg/kg/hr (16.67 - 83.33 mcg/kg/min) (using weight at time of admission) with an additional 2 mg/kg (2000 mcg/kg) bolus of ketamine
Active Comparator: SOC propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam
Standard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam.
Other: Standard of Care propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam
Standard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam administered according to the institutional SOC guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of ICP elevations greater than 22 mmHg for greater than 5 minutes
Time Frame: During the maximum 5-day course of study intervention, while patient is sedated and has intracranial pressure monitor in place in the ICU setting
ICP elevations > 22 mmHg for greater than 5 minutes.
During the maximum 5-day course of study intervention, while patient is sedated and has intracranial pressure monitor in place in the ICU setting
Mean ICP
Time Frame: During the maximum 5-day course of study intervention.
Mean ICP
During the maximum 5-day course of study intervention.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total time spent with intracranial pressure (ICP) >22 mmHg
Time Frame: During the maximum 5-day course of study intervention.
Total time spent with ICP >22 mmHg (in minutes).
During the maximum 5-day course of study intervention.
Mean Cerebral Perfusion Pressure (CPP)
Time Frame: During the maximum 5-day course of study intervention.
Mean CPP (in minutes).
During the maximum 5-day course of study intervention.
Total time spent with CPP <60 mmHg
Time Frame: During the maximum 5-day course of study intervention.
Total time spent with CPP <60 mmHg (in minutes).
During the maximum 5-day course of study intervention.
Total number of events where CPP <60 mmHg for greater than 5 minutes
Time Frame: During the maximum 5-day course of study intervention.
Total number of events where CPP <60 mmHg (in minutes) for greater than 5 minutes.
During the maximum 5-day course of study intervention.
Vasopressor dependency index (VDI)
Time Frame: During the maximum 5-day course of study intervention.
Relationship between vasopressor infusion dose and mean arterial blood pressure. VDI= (dobutamine dose × 1) + (dopamine dose × 1) + (norepinephrine dose × 100) + (vasopressin × 100) + (epinephrine × 100))/MAP indicating the relationship of high VDI and poor outcome.
During the maximum 5-day course of study intervention.
Incidence of seizures
Time Frame: During the maximum 5-day course of study intervention.
Incidence of seizures (as documented by EEG).
During the maximum 5-day course of study intervention.
Incidence of cardiac arrhythmias
Time Frame: During the maximum 5-day course of study intervention.
Incidence of cardiac arrhythmias (other than sinus tachycardia).
During the maximum 5-day course of study intervention.
Mean heart rate
Time Frame: During the maximum 5-day course of study intervention.
Mean heart rate (HR).
During the maximum 5-day course of study intervention.
Incidence of post-traumatic stress disorder (PTSD) in outpatient setting
Time Frame: Outpatient follow-up six months after intervention.
Incidence of PTSD at 6-month outpatient follow-up.
Outpatient follow-up six months after intervention.
Glasgow Coma Outcome Scale extended (GOSE-TBI) scores
Time Frame: Outpatient follow-up six months after intervention.
GOSE-TBI assessment resulting in subjective measure of 0-8 regarding recovery after injury with higher score indicating greatest recovery to pre-injury life, will be conducted at 6-month outpatient follow-up.
Outpatient follow-up six months after intervention.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

Collaborators

Uniformed Services University of the Health Sciences
Brooke Army Medical Center

Investigators

  • Principal Investigator: Bradley Dengler, MD, Uniformed Services University of the Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2024

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

April 16, 2024

First Submitted That Met QC Criteria

May 23, 2024

First Posted (Actual)

May 28, 2024

Study Record Updates

Last Update Posted (Actual)

July 14, 2025

Last Update Submitted That Met QC Criteria

July 10, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C.2024.025

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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