Ignite Creation Date:
2025-12-25 @ 3:33 AM
Ignite Modification Date:
2026-02-25 @ 7:22 PM
Study NCT ID:
NCT03743805
Status:
WITHDRAWN
Last Update Posted:
2024-10-31
First Post:
2018-11-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death Determination
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001926', 'term': 'Brain Death'}, {'id': 'D020925', 'term': 'Hypoxia-Ischemia, Brain'}, {'id': 'D006323', 'term': 'Heart Arrest'}, {'id': 'D003643', 'term': 'Death'}], 'ancestors': [{'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003128', 'term': 'Coma'}, {'id': 'D014474', 'term': 'Unconsciousness'}, {'id': 'D003244', 'term': 'Consciousness Disorders'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D002545', 'term': 'Brain Ischemia'}, {'id': 'D002561', 'term': 'Cerebrovascular Disorders'}, {'id': 'D002534', 'term': 'Hypoxia, Brain'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D000860', 'term': 'Hypoxia'}, {'id': 'D012818', 'term': 'Signs and Symptoms, Respiratory'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D006331', 'term': 'Heart Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D005442', 'term': 'Flumazenil'}, {'id': 'D009270', 'term': 'Naloxone'}], 'ancestors': [{'id': 'D001570', 'term': 'Benzodiazepinones'}, {'id': 'D001569', 'term': 'Benzodiazepines'}, {'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D009019', 'term': 'Morphinans'}, {'id': 'D053610', 'term': 'Opiate Alkaloids'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006572', 'term': 'Heterocyclic Compounds, Bridged-Ring'}, {'id': 'D006576', 'term': 'Heterocyclic Compounds, 4 or More Rings'}, {'id': 'D010616', 'term': 'Phenanthrenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'Insufficient patients', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2019-01-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-10', 'completionDateStruct': {'date': '2021-07-21', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-10-29', 'studyFirstSubmitDate': '2018-11-08', 'studyFirstSubmitQcDate': '2018-11-14', 'lastUpdatePostDateStruct': {'date': '2024-10-31', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-11-16', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-07-20', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Improved GCS scores or return of cerebral or brainstem functions in comatosed subjects', 'timeFrame': 'Within 30 minutes post treatment', 'description': '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'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['brain', 'death', 'sedative', 'narcotic'], 'conditions': ['Brain Death', 'Anoxic Brain Injury', 'Cardiac Arrest', 'Sedative Intoxication', 'Narcotic Intoxication']}, 'referencesModule': {'references': [{'pmid': '27907967', 'type': 'BACKGROUND', 'citation': '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': '25839719', 'type': 'BACKGROUND', 'citation': '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': '22194427', 'type': 'BACKGROUND', 'citation': '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': '11781400', 'type': 'BACKGROUND', 'citation': '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': '11309637', 'type': 'BACKGROUND', 'citation': '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': '7746373', 'type': 'BACKGROUND', 'citation': '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': '25854866', 'type': 'BACKGROUND', 'citation': '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': '20530327', 'type': 'BACKGROUND', 'citation': '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': '18077794', 'type': 'BACKGROUND', 'citation': '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': '24198290', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': "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", 'detailedDescription': "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.\n\nProspective 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 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.\n\nExclusion Criteria:\n\n* Spontaneous recovery of neurological functions, presence of seizures on EEG, individuals who are not yet adults, pregnant women and prisoners.'}, 'identificationModule': {'nctId': 'NCT03743805', 'briefTitle': 'Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death Determination', 'organization': {'class': 'OTHER', 'fullName': 'Prisma Health-Midlands'}, 'officialTitle': 'Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death Determination', 'orgStudyIdInfo': {'id': 'Pro00077995'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Reversal drugs', 'description': 'Flumazenil and naloxone', 'interventionNames': ['Drug: Flumazenil', 'Drug: Naloxone']}], 'interventions': [{'name': 'Flumazenil', 'type': 'DRUG', 'otherNames': ['Romazicon'], 'description': '0.2 mg IV push, which may be repeated every 20 minutes for up to a total of 1 mg', 'armGroupLabels': ['Reversal drugs']}, {'name': 'Naloxone', 'type': 'DRUG', 'otherNames': ['Narcan', 'Evzio'], 'description': '0.4 mg IV push, which may be repeated every 2 minutes for up to a total of 2 mg', 'armGroupLabels': ['Reversal drugs']}]}, 'contactsLocationsModule': {'locations': [{'zip': '29203', 'city': 'Columbia', 'state': 'South Carolina', 'country': 'United States', 'facility': 'PRISMA Health Midlands', 'geoPoint': {'lat': 34.00071, 'lon': -81.03481}}], 'overallOfficials': [{'name': 'Sameh R Hanna, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Palmetto Health-University of South Carolina Medical Group'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Prisma Health-Midlands', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}