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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03743805
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : March 26, 2019
Information provided by (Responsible Party):
Sameh Hanna, MD, Prisma Health-Midlands

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Brain Death Anoxic Brain Injury Cardiac Arrest Sedative Intoxication Narcotic Intoxication Drug: Flumazenil Drug: Naloxone Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death Determination
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine

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 Name: 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

Primary Outcome Measures :
  1. 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03743805

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Contact: Sameh R Hanna, MD 8643443439
Contact: Justin H Atwood, MD 8646084557

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United States, South Carolina
PRISMA Health Midlands Recruiting
Columbia, South Carolina, United States, 29203
Principal Investigator: Sameh R Hanna, MD         
Principal Investigator: Justin H Atwood, MD         
Sponsors and Collaborators
Sameh Hanna, MD
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Principal Investigator: Sameh R Hanna, MD Palmetto Health-University of South Carolina Medical Group

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Responsible Party: Sameh Hanna, MD, Pulmonary and Critical Care Fellow, Prisma Health-Midlands Identifier: NCT03743805    
Other Study ID Numbers: Pro00077995
First Posted: November 16, 2018    Key Record Dates
Last Update Posted: March 26, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Sameh Hanna, MD, Prisma Health-Midlands:
Additional relevant MeSH terms:
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Brain Injuries
Brain Death
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Pathologic Processes
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Protective Agents
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action