Ignite Creation Date:
2025-12-24 @ 10:54 PM
Ignite Modification Date:
2026-01-01 @ 4:14 PM
Study NCT ID:
NCT03260569
Status:
COMPLETED
Last Update Posted:
2025-04-30
First Post:
2017-08-22
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Inhaled Nitric Oxide in Brain Injury
Sponsor:
Organization:
Raw JSON
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'eventGroups': [{'id': 'EG000', 'title': 'Inhaled Nitric Oxide', 'description': 'received nitric oxide', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 0, 'seriousNumAtRisk': 6, 'deathsNumAffected': 3, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'did not receive iNO', 'otherNumAtRisk': 7, 'deathsNumAtRisk': 7, 'otherNumAffected': 0, 'seriousNumAtRisk': 7, 'deathsNumAffected': 2, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'PaO2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Inhaled Nitric Oxide', 'description': 'Inhaled nitric oxide at 20 parts per million, administered once during first 36 hours following admission\n\nInhaled Nitric Oxide: Patients randomized to this arm will receive inhaled nitric oxide 20 parts per million.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Nitrogen only, administered once during first 36 hours following admission\n\nPlacebo: Nitrogen plus oxygen'}], 'classes': [{'categories': [{'measurements': [{'value': '115', 'spread': '10', 'groupId': 'OG000'}, {'value': '95', 'spread': '10', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.05', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'at Day 3 of the study', 'description': 'The primary endpoint is the difference in PO2', 'unitOfMeasure': 'mmHg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'in Haled Nitric Oxide', 'description': 'received nitric oxide'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'did not receive iNO'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '7'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '7'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Inhaled Nitric Oxide', 'description': 'received nitric oxide'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'did not receive iNO'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '63', 'spread': '17', 'groupId': 'BG000'}, {'value': '49', 'spread': '20', 'groupId': 'BG001'}, {'value': '53', 'spread': '18', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'calculatePct': False, 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'description': 'Midwest', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2018-07-02', 'size': 396796, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_003.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2025-04-28T18:32', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR'], 'maskingDescription': 'Both nitric oxide and placebo nitrogen will be made available in unmarked cylinders.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Following initial non-invasive measurements, patients will be randomized to either an active treatment (inhaled nitric oxide at 30 parts per million) or placebo (nitrogen only). After two hours, measurements will be reassessed. If the patient remains on the mechanical ventilator at 72 hours post-admission, a third set of non-invasive measurements will be taken.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 13}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-12-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-04', 'completionDateStruct': {'date': '2023-12-28', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-04-28', 'studyFirstSubmitDate': '2017-08-22', 'resultsFirstSubmitDate': '2025-04-04', 'studyFirstSubmitQcDate': '2017-08-22', 'lastUpdatePostDateStruct': {'date': '2025-04-30', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-04-28', 'studyFirstPostDateStruct': {'date': '2017-08-24', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-04-30', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-12-28', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'PaO2', 'timeFrame': 'at Day 3 of the study', 'description': 'The primary endpoint is the difference in PO2'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Mechanical ventilation', 'Inhaled nitric oxide'], 'conditions': ['Traumatic Brain Injury']}, 'referencesModule': {'references': [{'pmid': '420436', 'type': 'BACKGROUND', 'citation': 'Schumacker PT, Rhodes GR, Newell JC, Dutton RE, Shah DM, Scovill WA, Powers SR. Ventilation-perfusion imbalance after head trauma. Am Rev Respir Dis. 1979 Jan;119(1):33-43. doi: 10.1164/arrd.1979.119.1.33.'}, {'pmid': '6346942', 'type': 'BACKGROUND', 'citation': 'Cooper KR, Boswell PA. Accurate measurement of functional residual capacity and oxygen consumption of patients on mechanical ventilation. Anaesth Intensive Care. 1983 May;11(2):151-7. doi: 10.1177/0310057X8301100212.'}, {'pmid': '17053881', 'type': 'BACKGROUND', 'citation': 'Koutsoukou A, Perraki H, Raftopoulou A, Koulouris N, Sotiropoulou C, Kotanidou A, Orfanos S, Roussos C. Respiratory mechanics in brain-damaged patients. Intensive Care Med. 2006 Dec;32(12):1947-54. doi: 10.1007/s00134-006-0406-0. Epub 2006 Oct 20.'}, {'pmid': '10199529', 'type': 'BACKGROUND', 'citation': 'Gruber A, Reinprecht A, Illievich UM, Fitzgerald R, Dietrich W, Czech T, Richling B. Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhage. Crit Care Med. 1999 Mar;27(3):505-14. doi: 10.1097/00003246-199903000-00026.'}, {'pmid': '12855888', 'type': 'BACKGROUND', 'citation': 'Holland MC, Mackersie RC, Morabito D, Campbell AR, Kivett VA, Patel R, Erickson VR, Pittet JF. The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury. J Trauma. 2003 Jul;55(1):106-11. doi: 10.1097/01.TA.0000071620.27375.BE.'}, {'pmid': '15659943', 'type': 'BACKGROUND', 'citation': 'Pelosi P, Severgnini P, Chiaranda M. An integrated approach to prevent and treat respiratory failure in brain-injured patients. Curr Opin Crit Care. 2005 Feb;11(1):37-42. doi: 10.1097/00075198-200502000-00006.'}, {'pmid': '25447937', 'type': 'BACKGROUND', 'citation': 'Garry PS, Ezra M, Rowland MJ, Westbrook J, Pattinson KT. The role of the nitric oxide pathway in brain injury and its treatment--from bench to bedside. Exp Neurol. 2015 Jan;263:235-43. doi: 10.1016/j.expneurol.2014.10.017. Epub 2014 Oct 29.'}, {'pmid': '23188422', 'type': 'BACKGROUND', 'citation': 'Terpolilli NA, Kim SW, Thal SC, Kuebler WM, Plesnila N. Inhaled nitric oxide reduces secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab. 2013 Feb;33(2):311-8. doi: 10.1038/jcbfm.2012.176. Epub 2012 Nov 28.'}, {'pmid': '19222848', 'type': 'BACKGROUND', 'citation': 'Papadimos TJ, Medhkour A, Yermal S. Successful use of inhaled nitric oxide to decrease intracranial pressure in a patient with severe traumatic brain injury complicated by acute respiratory distress syndrome: a role for an anti-inflammatory mechanism? Scand J Trauma Resusc Emerg Med. 2009 Feb 17;17:5. doi: 10.1186/1757-7241-17-5.'}, {'pmid': '18272001', 'type': 'BACKGROUND', 'citation': 'Papadimos TJ. The beneficial effects of inhaled nitric oxide in patients with severe traumatic brain injury complicated by acute respiratory distress syndrome: a hypothesis. J Trauma Manag Outcomes. 2008 Jan 14;2(1):1. doi: 10.1186/1752-2897-2-1.'}, {'pmid': '11473859', 'type': 'BACKGROUND', 'citation': 'Vavilala MS, Roberts JS, Moore AE, Newell DW, Lam AM. The influence of inhaled nitric oxide on cerebral blood flow and metabolism in a child with traumatic brain injury. Anesth Analg. 2001 Aug;93(2):351-3 , 3rd contents page. doi: 10.1097/00000539-200108000-00023.'}, {'pmid': '9428538', 'type': 'BACKGROUND', 'citation': 'Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K Jr, Hyers TM, Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med. 1998 Jan;26(1):15-23. doi: 10.1097/00003246-199801000-00011.'}, {'pmid': '10501745', 'type': 'BACKGROUND', 'citation': 'Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Intensive Care Med. 1999 Sep;25(9):911-9. doi: 10.1007/s001340050982.'}]}, 'descriptionModule': {'briefSummary': 'This study will evaluate the changes in respiratory mechanics following traumatic brain injury and determine the effect of inhaled nitric oxide on gas exchange.', 'detailedDescription': 'Intubation and mechanical ventilation are common treatments in the care of patients with traumatic brain injury (TBI). Intubation allows for airway control and facilitates removal of respiratory secretions. Mechanical ventilation allows control of arterial carbon dioxide to aid in control of intracranial pressure. Recent evidence suggests that lung protective ventilation (tidal volumes of 6 ml/kg of predicted body weight and moderate positive end expiratory pressure) improves outcomes following brain injury and reduces brain-lung cross talk.\n\nThe treatment of respiratory failure in TBI must balance the need to improve lung function with the negative consequences of increased intrathoracic pressure on mean arterial pressure, intracranial pressure and venous return. Traditional treatment of increasing positive end expiratory (PEEP) and mean airway pressure then, represent competing interests. Methods for improving arterial oxygenation while avoiding negative hemodynamic effects are needed.\n\nThe impact of head injury on respiratory mechanics has been studied in just a few clinical investigations. (1-3) Of note, the earliest of these noted that the ventilation perfusion (V/Q) matching following TBI was not the result of lung collapse or parenchymal lung disease but secondary to alterations in perfusion. There are three possibilities for this finding:\n\n1. redistribution in regional perfusion, which is partially mediated by the hypothalamus\n2. pulmonary microembolism, leading to increased dead space\n3. lung surfactant depletion due to excessive sympathetic stimulation and hyperventilation.\n\nThe introduction of inhaled pulmonary vasodilators such as inhaled nitric oxide or aerosolized epoprostenol offer an opportunity to improve oxygenation in patients with TBI without increasing airway pressures in the face of V/Q inequalities.\n\nThis study will evaluate the changes in respiratory mechanics following TBI and determine the effect of inhaled nitric oxide on gas exchange.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Hospital admission with traumatic brain injury (penetrating or blunt)\n* Requirement for mechanical ventilation\n* Glasgow Coma Score \\> 3\n\nExclusion Criteria:\n\n* Brain death\n* Expected survival \\< 48 hours\n* Air leak (bronchopleural fistula, tracheal injury)\n* Current inspired oxygen concentration (FiO2) \\> 0.65\n* Hemodynamic instability (systolic blood pressure \\< 100 mm Hg, cardiac arrhythmia)\n* Uncontrolled intracranial pressure (\\> 20 mm Hg)\n* Spinal cord injury with hypotension\n* Severe acute respiratory distress syndrome (ARDS) (PaO2/FiO2 \\< 100)\n* Chest abbreviated injury score (AIS) \\> 3\n* First rib fracture\n* Flail chest'}, 'identificationModule': {'nctId': 'NCT03260569', 'briefTitle': 'Inhaled Nitric Oxide in Brain Injury', 'organization': {'class': 'OTHER', 'fullName': 'University of Cincinnati'}, 'officialTitle': 'Respiratory Mechanics Following Brain Injury: The Role of Inhaled Nitric Oxide', 'orgStudyIdInfo': {'id': '2017 Goodman'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Inhaled Nitric Oxide', 'description': 'Inhaled nitric oxide at 20 parts per million, administered once during first 36 hours following admission', 'interventionNames': ['Drug: Inhaled Nitric Oxide']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Nitrogen only, administered once during first 36 hours following admission', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Inhaled Nitric Oxide', 'type': 'DRUG', 'description': 'Patients randomized to this arm will receive inhaled nitric oxide 20 parts per million.', 'armGroupLabels': ['Inhaled Nitric Oxide']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Nitrogen plus oxygen', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '45267', 'city': 'Cincinnati', 'state': 'Ohio', 'country': 'United States', 'facility': 'University of Cincinnati', 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Cincinnati', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Instructor', 'investigatorFullName': 'Michael Goodman', 'investigatorAffiliation': 'University of Cincinnati'}}}}