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

NCT03743805 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: Pro00077995
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Conditions

Brain Death; Anoxic Brain Injury; Cardiac Arrest; Sedative Intoxication; Narcotic Intoxication

Keywords

brain; death; sedative; narcotic

Outcome Measures

Primary Outcomes (1)

• Improved GCS scores or return of cerebral or brainstem functions in comatosed subjects

  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

Study Arms (1)

Reversal drugs

EXPERIMENTAL

Flumazenil and naloxone

Drug: Flumazenil; Drug: Naloxone

Interventions

Flumazenil DRUG

0.2 mg IV push, which may be repeated every 20 minutes for up to a total of 1 mg

Also known as: Romazicon

Reversal drugs

Naloxone DRUG

0.4 mg IV push, which may be repeated every 2 minutes for up to a total of 2 mg

Also known as: Narcan, Evzio

Reversal drugs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Prisma Health-Midlands: lead

Study Sites (1)

PRISMA Health Midlands

Columbia, South Carolina, 29203, United States

Location

Related Publications (10)

• Varelas PN, Lewis A. Modern Approach to Brain Death. Semin Neurol. 2016 Dec;36(6):625-630. doi: 10.1055/s-0036-1592317. Epub 2016 Dec 1.

  PMID: 27907967 BACKGROUND

• Wijdicks EF. Brain death guidelines explained. Semin Neurol. 2015 Apr;35(2):105-15. doi: 10.1055/s-0035-1547532. Epub 2015 Apr 3.

  PMID: 25839719 BACKGROUND

• Gardiner D, Shemie S, Manara A, Opdam H. International perspective on the diagnosis of death. Br J Anaesth. 2012 Jan;108 Suppl 1:i14-28. doi: 10.1093/bja/aer397.

  PMID: 22194427 BACKGROUND

• Wijdicks EF. Brain death worldwide: accepted fact but no global consensus in diagnostic criteria. Neurology. 2002 Jan 8;58(1):20-5. doi: 10.1212/wnl.58.1.20.

  PMID: 11781400 BACKGROUND

• Wijdicks EF. The diagnosis of brain death. N Engl J Med. 2001 Apr 19;344(16):1215-21. doi: 10.1056/NEJM200104193441606. No abstract available.

  PMID: 11309637 BACKGROUND

• Wijdicks EF. Determining brain death in adults [RETIRED]. Neurology. 1995 May;45(5):1003-11. doi: 10.1212/wnl.45.5.1003. No abstract available.

  PMID: 7746373 BACKGROUND

• Wahlster S, Wijdicks EF, Patel PV, Greer DM, Hemphill JC 3rd, Carone M, Mateen FJ. Brain death declaration: Practices and perceptions worldwide. Neurology. 2015 May 5;84(18):1870-9. doi: 10.1212/WNL.0000000000001540. Epub 2015 Apr 8.

  PMID: 25854866 BACKGROUND

• Wijdicks EF, Varelas PN, Gronseth GS, Greer DM; American Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010 Jun 8;74(23):1911-8. doi: 10.1212/WNL.0b013e3181e242a8.

  PMID: 20530327 BACKGROUND

• Greer DM, Varelas PN, Haque S, Wijdicks EF. Variability of brain death determination guidelines in leading US neurologic institutions. Neurology. 2008 Jan 22;70(4):284-9. doi: 10.1212/01.wnl.0000296278.59487.c2. Epub 2007 Dec 12.

  PMID: 18077794 BACKGROUND

• Shappell CN, Frank JI, Husari K, Sanchez M, Goldenberg F, Ardelt A. Practice variability in brain death determination: a call to action. Neurology. 2013 Dec 3;81(23):2009-14. doi: 10.1212/01.wnl.0000436938.70528.4a. Epub 2013 Nov 6.

  PMID: 24198290 BACKGROUND

MeSH Terms

Conditions

Brain Death; Hypoxia-Ischemia, Brain; Heart Arrest; Death

Interventions

Flumazenil; Naloxone

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Coma; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Brain Ischemia; Cerebrovascular Disorders; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Heart Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Sameh R Hanna, MD

  Palmetto Health-University of South Carolina Medical Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 16, 2018
• Study Start: January 1, 2019
• Primary Completion: July 20, 2021
• Study Completion: July 21, 2021
• Last Updated: October 31, 2024

Record last verified: 2024-10

Locations

US (1)