Ignite Creation Date:
2025-12-24 @ 6:56 PM
Ignite Modification Date:
2026-01-05 @ 5:21 PM
Study NCT ID:
NCT06429657
Status:
SUSPENDED
Last Update Posted:
2025-07-14
First Post:
2024-04-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Ketamine for Sedation in Severe Traumatic Brain Injury
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000070642', 'term': 'Brain Injuries, Traumatic'}, {'id': 'D019586', 'term': 'Intracranial Hypertension'}, {'id': 'D020299', 'term': 'Intracranial Hemorrhage, Hypertensive'}], 'ancestors': [{'id': 'D001930', 'term': 'Brain Injuries'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D006259', 'term': 'Craniocerebral Trauma'}, {'id': 'D020196', 'term': 'Trauma, Nervous System'}, {'id': 'D014947', 'term': 'Wounds and Injuries'}, {'id': 'D020300', 'term': 'Intracranial Hemorrhages'}, {'id': 'D002561', 'term': 'Cerebrovascular Disorders'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D007649', 'term': 'Ketamine'}, {'id': 'D015742', 'term': 'Propofol'}, {'id': 'D005283', 'term': 'Fentanyl'}, {'id': 'D020927', 'term': 'Dexmedetomidine'}, {'id': 'D009020', 'term': 'Morphine'}, {'id': 'D004091', 'term': 'Hydromorphone'}, {'id': 'D008874', 'term': 'Midazolam'}, {'id': 'D008140', 'term': 'Lorazepam'}], 'ancestors': [{'id': 'D003510', 'term': 'Cyclohexanes'}, {'id': 'D003516', 'term': 'Cycloparaffins'}, {'id': 'D006840', 'term': 'Hydrocarbons, Alicyclic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D010636', 'term': 'Phenols'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D010880', 'term': 'Piperidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D009022', 'term': 'Morphine Derivatives'}, {'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': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D010616', 'term': 'Phenanthrenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D001569', 'term': 'Benzodiazepines'}, {'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D001570', 'term': 'Benzodiazepinones'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 50}}, 'statusModule': {'whyStopped': 'administrative hold at current open site and awaiting site startup at additional participating sites', 'overallStatus': 'SUSPENDED', 'startDateStruct': {'date': '2024-09-23', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2027-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-10', 'studyFirstSubmitDate': '2024-04-16', 'studyFirstSubmitQcDate': '2024-05-23', 'lastUpdatePostDateStruct': {'date': '2025-07-14', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-05-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-01-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of ICP elevations greater than 22 mmHg for greater than 5 minutes', 'timeFrame': 'During the maximum 5-day course of study intervention, while patient is sedated and has intracranial pressure monitor in place in the ICU setting', 'description': 'ICP elevations \\> 22 mmHg for greater than 5 minutes.'}, {'measure': 'Mean ICP', 'timeFrame': 'During the maximum 5-day course of study intervention.', 'description': 'Mean ICP'}], 'secondaryOutcomes': [{'measure': 'Total time spent with intracranial pressure (ICP) >22 mmHg', 'timeFrame': 'During the maximum 5-day course of study intervention.', 'description': 'Total time spent with ICP \\>22 mmHg (in minutes).'}, {'measure': 'Mean Cerebral Perfusion Pressure (CPP)', 'timeFrame': 'During the maximum 5-day course of study intervention.', 'description': 'Mean CPP (in minutes).'}, {'measure': 'Total time spent with CPP <60 mmHg', 'timeFrame': 'During the maximum 5-day course of study intervention.', 'description': 'Total time spent with CPP \\<60 mmHg (in minutes).'}, {'measure': 'Total number of events where CPP <60 mmHg for greater than 5 minutes', 'timeFrame': 'During the maximum 5-day course of study intervention.', 'description': 'Total number of events where CPP \\<60 mmHg (in minutes) for greater than 5 minutes.'}, {'measure': 'Vasopressor dependency index (VDI)', 'timeFrame': 'During the maximum 5-day course of study intervention.', 'description': '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.'}, {'measure': 'Incidence of seizures', 'timeFrame': 'During the maximum 5-day course of study intervention.', 'description': 'Incidence of seizures (as documented by EEG).'}, {'measure': 'Incidence of cardiac arrhythmias', 'timeFrame': 'During the maximum 5-day course of study intervention.', 'description': 'Incidence of cardiac arrhythmias (other than sinus tachycardia).'}, {'measure': 'Mean heart rate', 'timeFrame': 'During the maximum 5-day course of study intervention.', 'description': 'Mean heart rate (HR).'}, {'measure': 'Incidence of post-traumatic stress disorder (PTSD) in outpatient setting', 'timeFrame': 'Outpatient follow-up six months after intervention.', 'description': 'Incidence of PTSD at 6-month outpatient follow-up.'}, {'measure': 'Glasgow Coma Outcome Scale extended (GOSE-TBI) scores', 'timeFrame': 'Outpatient follow-up six months after intervention.', 'description': '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.'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['TBI', 'Severe TBI', 'Traumatic Brain Injury', 'Sedation', 'Ketamine'], 'conditions': ['Severe Traumatic Brain Injury', 'Intracranial Hypertension', 'Intracranial Hemorrhage, Hypertensive']}, 'referencesModule': {'references': [{'pmid': '30182649', 'type': 'BACKGROUND', 'citation': 'Iaccarino C, Carretta A, Nicolosi F, Morselli C. Epidemiology of severe traumatic brain injury. J Neurosurg Sci. 2018 Oct;62(5):535-541. doi: 10.23736/S0390-5616.18.04532-0.'}, {'pmid': '26414629', 'type': 'BACKGROUND', 'citation': 'Agrawal D, Raghavendran K, Schaubel DE, Mishra MC, Rajajee V. A Propensity Score Analysis of the Impact of Invasive Intracranial Pressure Monitoring on Outcomes after Severe Traumatic Brain Injury. J Neurotrauma. 2016 May 1;33(9):853-8. doi: 10.1089/neu.2015.4015. Epub 2015 Oct 8.'}, {'pmid': '17375994', 'type': 'BACKGROUND', 'citation': 'Butcher I, Maas AI, Lu J, Marmarou A, Murray GD, Mushkudiani NA, McHugh GS, Steyerberg EW. Prognostic value of admission blood pressure in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007 Feb;24(2):294-302. doi: 10.1089/neu.2006.0032.'}, {'pmid': '17375993', 'type': 'BACKGROUND', 'citation': 'McHugh GS, Engel DC, Butcher I, Steyerberg EW, Lu J, Mushkudiani N, Hernandez AV, Marmarou A, Maas AI, Murray GD. Prognostic value of secondary insults in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007 Feb;24(2):287-93. doi: 10.1089/neu.2006.0031.'}, {'pmid': '17375997', 'type': 'BACKGROUND', 'citation': 'Murray GD, Butcher I, McHugh GS, Lu J, Mushkudiani NA, Maas AI, Marmarou A, Steyerberg EW. Multivariable prognostic analysis in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007 Feb;24(2):329-37. doi: 10.1089/neu.2006.0035.'}, {'pmid': '31583962', 'type': 'BACKGROUND', 'citation': 'Petkus V, Preiksaitis A, Chaleckas E, Chomskis R, Zubaviciute E, Vosylius S, Rocka S, Rastenyte D, Aries MJ, Ragauskas A, Neumann JO. Optimal Cerebral Perfusion Pressure: Targeted Treatment for Severe Traumatic Brain Injury. J Neurotrauma. 2020 Jan 15;37(2):389-396. doi: 10.1089/neu.2019.6551. Epub 2019 Nov 13.'}, {'pmid': '27654000', 'type': 'BACKGROUND', 'citation': "Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM, Shutter L, Tasker RC, Vavilala MS, Wilberger J, Wright DW, Ghajar J. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017 Jan 1;80(1):6-15. doi: 10.1227/NEU.0000000000001432."}, {'pmid': '21434843', 'type': 'BACKGROUND', 'citation': "Cooper DJ, Rosenfeld JV, Murray L, Arabi YM, Davies AR, D'Urso P, Kossmann T, Ponsford J, Seppelt I, Reilly P, Wolfe R; DECRA Trial Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011 Apr 21;364(16):1493-502. doi: 10.1056/NEJMoa1102077. Epub 2011 Mar 25."}, {'pmid': '31659383', 'type': 'BACKGROUND', 'citation': 'Hawryluk GWJ, Aguilera S, Buki A, Bulger E, Citerio G, Cooper DJ, Arrastia RD, Diringer M, Figaji A, Gao G, Geocadin R, Ghajar J, Harris O, Hoffer A, Hutchinson P, Joseph M, Kitagawa R, Manley G, Mayer S, Menon DK, Meyfroidt G, Michael DB, Oddo M, Okonkwo D, Patel M, Robertson C, Rosenfeld JV, Rubiano AM, Sahuquillo J, Servadei F, Shutter L, Stein D, Stocchetti N, Taccone FS, Timmons S, Tsai E, Ullman JS, Vespa P, Videtta W, Wright DW, Zammit C, Chesnut RM. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med. 2019 Dec;45(12):1783-1794. doi: 10.1007/s00134-019-05805-9. 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Brief episodes of intracranial hypertension and cerebral hypoperfusion are associated with poor functional outcome after severe traumatic brain injury. J Trauma. 2011 Aug;71(2):364-73; discussion 373-4. doi: 10.1097/TA.0b013e31822820da.'}, {'pmid': '4672167', 'type': 'BACKGROUND', 'citation': 'Gardner AE, Dannemiller FJ, Dean D. Intracranial cerebrospinal fluid pressure in man during ketamine anesthesia. Anesth Analg. 1972 Sep-Oct;51(5):741-5. No abstract available.'}, {'pmid': '4650346', 'type': 'BACKGROUND', 'citation': 'Gibbs JM. The effect of intravenous ketamine on cerebrospinal fluid pressure. Br J Anaesth. 1972 Dec;44(12):1298-302. doi: 10.1093/bja/44.12.1298. No abstract available.'}, {'pmid': '25245275', 'type': 'BACKGROUND', 'citation': 'Green SM, Andolfatto G, Krauss BS. Ketamine and intracranial pressure: no contraindication except hydrocephalus. Ann Emerg Med. 2015 Jan;65(1):52-4. doi: 10.1016/j.annemergmed.2014.08.025. Epub 2014 Sep 20. No abstract available.'}, {'pmid': '32328972', 'type': 'BACKGROUND', 'citation': 'Gregers MCT, Mikkelsen S, Lindvig KP, Brochner AC. Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review. Neurocrit Care. 2020 Aug;33(1):273-282. doi: 10.1007/s12028-020-00975-7.'}, {'pmid': '36825892', 'type': 'BACKGROUND', 'citation': 'Laws JC, Vance EH, Betters KA, Anderson JJ, Fleishman S, Bonfield CM, Wellons JC 3rd, Xu M, Slaughter JC, Giuse DA, Patel N, Jordan LC, Wolf MS. Acute Effects of Ketamine on Intracranial Pressure in Children With Severe Traumatic Brain Injury. Crit Care Med. 2023 May 1;51(5):563-572. doi: 10.1097/CCM.0000000000005806. Epub 2023 Feb 21.'}, {'pmid': '35637760', 'type': 'BACKGROUND', 'citation': 'Dengler BA, Karam O, Barthol CA, Chance A, Snider LE, Mundy CM, Bounajem MT, Johnson WC, Maita MM, Mendez-Gomez PM, Seifi A, Hafeez S. 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Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil. Crit Care Med. 2003 Mar;31(3):711-7. doi: 10.1097/01.CCM.0000044505.24727.16.'}, {'pmid': '15818105', 'type': 'BACKGROUND', 'citation': 'Bourgoin A, Leone M, Delmas A, Garnier F, Albanese J, Martin C. Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med. 2005 Apr;33(4):780-6. doi: 10.1097/01.ccm.0000157788.20591.23.'}, {'pmid': '8955439', 'type': 'BACKGROUND', 'citation': 'Kolenda H, Gremmelt A, Rading S, Braun U, Markakis E. Ketamine for analgosedative therapy in intensive care treatment of head-injured patients. Acta Neurochir (Wien). 1996;138(10):1193-9. doi: 10.1007/BF01809750.'}, {'pmid': '17893578', 'type': 'BACKGROUND', 'citation': 'Schmittner MD, Vajkoczy SL, Horn P, Bertsch T, Quintel M, Vajkoczy P, Muench E. Effects of fentanyl and S(+)-ketamine on cerebral hemodynamics, gastrointestinal motility, and need of vasopressors in patients with intracranial pathologies: a pilot study. J Neurosurg Anesthesiol. 2007 Oct;19(4):257-62. doi: 10.1097/ANA.0b013e31811f3feb.'}, {'pmid': '21829786', 'type': 'BACKGROUND', 'citation': 'Sakpal TV. Sample size estimation in clinical trial. Perspect Clin Res. 2010 Apr;1(2):67-9.'}, {'type': 'BACKGROUND', 'citation': 'Military Health System and Defense Health Agency. DOD TBI Worldwide Numbers: Traumatic Brain Injury Center of Excellence; 2022 [Available from: https://health.mil/Military-Health-Topics/Centers-of-Excellence/Traumatic-Brain-Injury-Center-of-Excellence/DOD-TBI-Worldwide-NumbersTraumaticBrain].'}, {'type': 'BACKGROUND', 'citation': 'Michalczyk, Lukasz, and Lukasz Kaczmarek.'}, {'type': 'BACKGROUND', 'citation': 'Chan, Kai En, et al.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "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.\n\nPatients 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.\n\nThis 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.\n\nThe research team will performed one outpatient follow-up after study intervention ends."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Adults 18-65 years of age\n* Severe traumatic brain injury (TBI), with a Glasgow Coma Scale (GCS) ≤ 8, requiring intracranial monitoring\n* Placement of intracranial pressure monitor\n* Receiving treatment in an intensive care unit (ICU)\n\nExclusion Criteria:\n\n* Significant cardiovascular disease with recent coronary intervention\n* Pregnancy\n* Prisoners\n* Known allergy to ketamine or propofol'}, 'identificationModule': {'nctId': 'NCT06429657', 'acronym': 'Ketamine', 'briefTitle': 'Ketamine for Sedation in Severe Traumatic Brain Injury', 'organization': {'class': 'OTHER', 'fullName': 'Henry M. Jackson Foundation for the Advancement of Military Medicine'}, 'officialTitle': 'Ketamine for Sedation in Severe Traumatic Brain Injury', 'orgStudyIdInfo': {'id': 'C.2024.025'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Ketamine with propofol', 'description': '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', 'interventionNames': ['Drug: Ketamine with propofol']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'SOC propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam', 'description': 'Standard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam.', 'interventionNames': ['Other: Standard of Care propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam']}], 'interventions': [{'name': 'Ketamine with propofol', 'type': 'DRUG', 'description': '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', 'armGroupLabels': ['Ketamine with propofol']}, {'name': 'Standard of Care propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam', 'type': 'OTHER', 'description': 'Standard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam administered according to the institutional SOC guidelines.', 'armGroupLabels': ['SOC propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam']}]}, 'contactsLocationsModule': {'locations': [{'zip': '78234', 'city': 'Fort Sam Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'Brooke Army Medical Center', 'geoPoint': {'lat': 29.45303, 'lon': -98.4417}}], 'overallOfficials': [{'name': 'Bradley Dengler, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Uniformed Services University of the Health Sciences'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Henry M. Jackson Foundation for the Advancement of Military Medicine', 'class': 'OTHER'}, 'collaborators': [{'name': 'Uniformed Services University of the Health Sciences', 'class': 'FED'}, {'name': 'Brooke Army Medical Center', 'class': 'FED'}], 'responsibleParty': {'type': 'SPONSOR'}}}}