Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death Determination

October 29, 2024 updated by: Prisma Health-Midlands
Current standard of care prior to determination of brain death in subjects with suspected anoxic brain injury is to exclude complicating medical conditions that may confound clinical assessment (such as severe electrolyte, acid base, endocrine or circulatory disturbance), achieve normothermia and normal systolic blood pressure over 100 mmHg (with or without vasopressor use), exclude the presence of neuromuscular blocking agents (with the presence of a train of 4 twitches with maximal ulnar nerve stimulation) as well as to exclude the presence of CNS depressant drug effects. At the present time the latter is done by history, drug screen and allowing enough time for paralytic and sedative drugs to be metabolized and cleared from the body. Clearance is calculated by using 5 times the drug's half-life assuming normal hepatic and renal functions. Half-life can also be prolonged in subjects who have been treated with induced hypothermia. Literature search revealed articles with general guidelines and approaches to brain death, but none addressed pharmacological reversal of sedative drugs

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Question of proposed study is whether a subject's comatose state is secondary to delayed clearance of a previously administered CNS depressant. By using pharmacologic reversal agents of commonly used benzodiazepines and opioids, the investigators aim to identify participants that may likely improve after complete clearance of the drugs from their system.

Prospective trial with enrollment of 30 subjects in 2 intensive care units at Palmetto Health Richland from January 1st 2019 to June 30th 2020. Research procedures will be performed in the intensive care setting. If participants had undergone targeted temperature management (33-36 degrees Celsius for 24 hours via intravascular or surface control methods, with or without sedation or neuromuscular blockade, followed by rewarming actively or passively at 0.25-0.5 degrees per hour over 8-12 hours to 37 degrees) investigators will wait 24 hours after rewarming prior to testing. End point is to evaluate if pharmacological reversal agents would result in improved GCS scores or return of cerebral or brainstem functions in some comatose subjects, which will be considered a positive test result.

Study Type

Interventional

Phase

  • Early Phase 1

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
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Midlands

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Adults with cardiac arrest who may have completed targeted temperature management (hypothermia protocol) and have had no neurological recovery after 24 hours of rewarming will be enrolled. Subjects will have a suspected diagnosis of anoxic brain injury secondary to cardiac arrest, and seizures ruled out with an EEG. All subjects are expected to be unable to consent and consent will be obtained from their legal authorized representative.

Exclusion Criteria:

  • Spontaneous recovery of neurological functions, presence of seizures on EEG, individuals who are not yet adults, pregnant women and prisoners.

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: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Reversal drugs
Flumazenil and naloxone
Drug: Flumazenil
0.2 mg IV push, which may be repeated every 20 minutes for up to a total of 1 mg
Other Names:
  • Romazicon
Drug: Naloxone
0.4 mg IV push, which may be repeated every 2 minutes for up to a total of 2 mg
Other Names:
  • Narcan
  • Evzio

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improved GCS scores or return of cerebral or brainstem functions in comatosed subjects
Time Frame: Within 30 minutes post treatment
Subjects will be observed closely and tested before and after intervention for any signs of cerebral or brainstem function (1-Response to pain stimulus with earlobe pinching, trapezius squeezing and sternal rub or other brain-originating movements, e.g. seizures, decerebrate or decorticate posturing. 2-Pupillary light reflex with bright light. 3-Corneal reflexes with the use of cotton swab or tissue paper. 4-Gag reflex with a tongue depressor looking for bilateral palatal elevation. 5-Cough with tracheal suctioning at the carinal level) and GCS re-evaluated
Within 30 minutes post treatment

Collaborators and Investigators

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

Sponsor

Prisma Health-Midlands

Investigators

  • Principal Investigator: Sameh R Hanna, MD, Palmetto Health-University of South Carolina Medical Group

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)

January 1, 2019

Primary Completion (Estimated)

July 20, 2021

Study Completion (Actual)

July 21, 2021

Study Registration Dates

First Submitted

November 8, 2018

First Submitted That Met QC Criteria

November 14, 2018

First Posted (Actual)

November 16, 2018

Study Record Updates

Last Update Posted (Actual)

October 31, 2024

Last Update Submitted That Met QC Criteria

October 29, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00077995

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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