Ignite Creation Date:
2025-12-24 @ 11:30 PM
Ignite Modification Date:
2026-01-05 @ 5:31 PM
Study NCT ID:
NCT02899156
Status:
TERMINATED
Last Update Posted:
2020-07-23
First Post:
2016-07-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Flumazenil for Hypoactive Delirium Secondary to Benzodiazepine Exposure
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003693', 'term': 'Delirium'}], 'ancestors': [{'id': 'D003221', 'term': 'Confusion'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D005442', 'term': 'Flumazenil'}], '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'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'kjschomer@ucdavis.edu', 'phone': '916-734-2243', 'title': 'Kendra Schomer, PharmD', 'organization': 'University of California Davis Medical Center'}, 'certainAgreement': {'piSponsorEmployee': True, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'A planned interim analysis led to the trial being stopped early based on the observed size effect and power analysis.'}}, 'adverseEventsModule': {'timeFrame': '72 hours while on study infusion', 'eventGroups': [{'id': 'EG000', 'title': 'Flumazenil Group', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil', 'otherNumAtRisk': 11, 'deathsNumAtRisk': 11, 'otherNumAffected': 0, 'seriousNumAtRisk': 11, 'deathsNumAffected': 1, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo Group', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline', 'otherNumAtRisk': 11, 'deathsNumAtRisk': 11, 'otherNumAffected': 0, 'seriousNumAtRisk': 11, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Delirium-free Days', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Flumazenil Group', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil'}, {'id': 'OG001', 'title': 'Placebo Group', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline'}], 'classes': [{'categories': [{'measurements': [{'value': '12.7', 'groupId': 'OG000', 'lowerLimit': '7.2', 'upperLimit': '13.2'}, {'value': '9.2', 'groupId': 'OG001', 'lowerLimit': '0', 'upperLimit': '10.2'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'up to 14 days after randomization', 'description': 'Defined by the number of days in the 14-day period after randomization that the patient was alive and not delirious (i.e. CAM-ICU negative). Zero delirium-free days will be observed for patients that die within the 14-day period.', 'unitOfMeasure': 'days', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'One patient randomized to the flumazenil and one randomized to the placebo never received the study infusion. The patient in the flumazenil group died from a massive hemorrhage within 1 hour of infusion initiation, and it was deemed nonattributable to study infusion. Twenty patients were included in the final analysis.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Delirium Resolution', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Flumazenil Group', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil'}, {'id': 'OG001', 'title': 'Placebo Group', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline'}], 'classes': [{'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'up to 14 days after randomization', 'description': 'defined by the proportion of patients who were delirium free at 14 days after randomization', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Intensive Care Unit Length of Stay', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Flumazenil Group', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil'}, {'id': 'OG001', 'title': 'Placebo Group', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline'}], 'classes': [{'categories': [{'measurements': [{'value': '7.8', 'spread': '4.8', 'groupId': 'OG000'}, {'value': '7', 'spread': '6', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'duration of admission to the intensive care unit', 'description': 'length of time that the patient was admitted to an intensive care unit service during the hospital stay', 'unitOfMeasure': 'days', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Mechanical Ventilator Free Days', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Flumazenil Group', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil'}, {'id': 'OG001', 'title': 'Placebo Group', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline'}], 'classes': [{'categories': [{'measurements': [{'value': '23.6', 'spread': '4.4', 'groupId': 'OG000'}, {'value': '24.9', 'spread': '5', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 28 days after randomization', 'description': 'number of days within the first 28 days after enrollment that the patient was free from needing mechanical ventilation', 'unitOfMeasure': 'days', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Occurrence of Agitation Requiring Use of Rescue Sedatives While on Study Infusion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Flumazenil Group', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil'}, {'id': 'OG001', 'title': 'Placebo Group', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'up to 72 hours after the start of the infusion', 'description': 'number of times that a RASS score of + 2 to +4 occurred that did not resolve with decreasing study infusion', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Average Duration of Study Infusion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Flumazenil Group', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil'}, {'id': 'OG001', 'title': 'Placebo Group', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline'}], 'classes': [{'categories': [{'measurements': [{'value': '54.8', 'spread': '16.8', 'groupId': 'OG000'}, {'value': '58.2', 'spread': '23.5', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 72 hours after the start of the infusion', 'description': 'average duration of time patient was randomized to each infusion up to 72 hours', 'unitOfMeasure': 'hours', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Average Maximum Rate of Study Infusion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Flumazenil Group', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil'}, {'id': 'OG001', 'title': 'Placebo Group', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline'}], 'classes': [{'categories': [{'measurements': [{'value': '5', 'spread': '2', 'groupId': 'OG000'}, {'value': '5.2', 'spread': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 72 hours after the start of the infusion', 'description': 'average maximum rate (ml/hr) during the 72 hours after study infusion', 'unitOfMeasure': 'milliliters per hour', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Flumazenil Group', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil'}, {'id': 'FG001', 'title': 'Placebo Group', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Flumazenil Infusion', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nFlumazenil'}, {'id': 'BG001', 'title': 'Placebo Infusion', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.\n\nPlacebo: 0.9% normal saline'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '58', 'spread': '7', 'groupId': 'BG000'}, {'value': '59.4', 'spread': '7.6', 'groupId': 'BG001'}, {'value': '58.9', 'spread': '7.2', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Days in Hospital Prior to Enrollment', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '8.5', 'spread': '2.8', 'groupId': 'BG000'}, {'value': '10.6', 'spread': '7.5', 'groupId': 'BG001'}, {'value': '9.5', 'spread': '5.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'days', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Time Since Last Benzodiazepine', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '43', 'spread': '23', 'groupId': 'BG000'}, {'value': '55', 'spread': '37.1', 'groupId': 'BG001'}, {'value': '49', 'spread': '31.5', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'hours', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Lorazepam Equivalents', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '117', 'groupId': 'BG000', 'lowerLimit': '85.8', 'upperLimit': '476'}, {'value': '110.3', 'groupId': 'BG001', 'lowerLimit': '57', 'upperLimit': '221'}, {'value': '113.6', 'groupId': 'BG002', 'lowerLimit': '68.6', 'upperLimit': '284.3'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'milligrams', 'dispersionType': 'INTER_QUARTILE_RANGE'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2017-09-25', 'size': 188542, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2020-06-05T22:30', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 22}}, 'statusModule': {'whyStopped': 'A planned interim analysis led to the trial being stopped early based on the observed size effect and power analysis.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2016-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-07', 'completionDateStruct': {'date': '2019-04-16', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-07-08', 'studyFirstSubmitDate': '2016-07-27', 'resultsFirstSubmitDate': '2020-06-09', 'studyFirstSubmitQcDate': '2016-09-08', 'lastUpdatePostDateStruct': {'date': '2020-07-23', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-07-08', 'studyFirstPostDateStruct': {'date': '2016-09-14', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2020-07-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-04-16', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Delirium-free Days', 'timeFrame': 'up to 14 days after randomization', 'description': 'Defined by the number of days in the 14-day period after randomization that the patient was alive and not delirious (i.e. CAM-ICU negative). Zero delirium-free days will be observed for patients that die within the 14-day period.'}], 'secondaryOutcomes': [{'measure': 'Number of Participants With Delirium Resolution', 'timeFrame': 'up to 14 days after randomization', 'description': 'defined by the proportion of patients who were delirium free at 14 days after randomization'}, {'measure': 'Intensive Care Unit Length of Stay', 'timeFrame': 'duration of admission to the intensive care unit', 'description': 'length of time that the patient was admitted to an intensive care unit service during the hospital stay'}, {'measure': 'Number of Mechanical Ventilator Free Days', 'timeFrame': 'up to 28 days after randomization', 'description': 'number of days within the first 28 days after enrollment that the patient was free from needing mechanical ventilation'}, {'measure': 'Occurrence of Agitation Requiring Use of Rescue Sedatives While on Study Infusion', 'timeFrame': 'up to 72 hours after the start of the infusion', 'description': 'number of times that a RASS score of + 2 to +4 occurred that did not resolve with decreasing study infusion'}, {'measure': 'Average Duration of Study Infusion', 'timeFrame': 'up to 72 hours after the start of the infusion', 'description': 'average duration of time patient was randomized to each infusion up to 72 hours'}, {'measure': 'Average Maximum Rate of Study Infusion', 'timeFrame': 'up to 72 hours after the start of the infusion', 'description': 'average maximum rate (ml/hr) during the 72 hours after study infusion'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['delirium', 'flumazenil', 'hypoactive delirium', 'benzodiazepine', 'benzodiazepine antagonist', 'critical care'], 'conditions': ['Hypoactive Delirium']}, 'referencesModule': {'references': [{'pmid': '16394685', 'type': 'BACKGROUND', 'citation': 'Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006 Jan;104(1):21-6. doi: 10.1097/00000542-200601000-00005.'}, {'pmid': '26404392', 'type': 'BACKGROUND', 'citation': 'Zaal IJ, Devlin JW, Hazelbag M, Klein Klouwenberg PM, van der Kooi AW, Ong DS, Cremer OL, Groenwold RH, Slooter AJ. Benzodiazepine-associated delirium in critically ill adults. Intensive Care Med. 2015 Dec;41(12):2130-7. doi: 10.1007/s00134-015-4063-z. Epub 2015 Sep 24.'}, {'pmid': '22859526', 'type': 'BACKGROUND', 'citation': 'Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012 Oct 15;186(8):724-31. doi: 10.1164/rccm.201203-0522OC. Epub 2012 Aug 2.'}, {'pmid': '15082703', 'type': 'BACKGROUND', 'citation': 'Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753.'}, {'pmid': '24423152', 'type': 'BACKGROUND', 'citation': 'Patel SB, Poston JT, Pohlman A, Hall JB, Kress JP. Rapidly reversible, sedation-related delirium versus persistent delirium in the intensive care unit. Am J Respir Crit Care Med. 2014 Mar 15;189(6):658-65. doi: 10.1164/rccm.201310-1815OC.'}, {'pmid': '1724638', 'type': 'BACKGROUND', 'citation': 'Brogden RN, Goa KL. Flumazenil. A reappraisal of its pharmacological properties and therapeutic efficacy as a benzodiazepine antagonist. Drugs. 1991 Dec;42(6):1061-89. doi: 10.2165/00003495-199142060-00010.'}, {'pmid': '1597024', 'type': 'BACKGROUND', 'citation': 'Breheny FX. Reversal of midazolam sedation with flumazenil. Crit Care Med. 1992 Jun;20(6):736-9. doi: 10.1097/00003246-199206000-00006.'}, {'pmid': '2110788', 'type': 'BACKGROUND', 'citation': 'Pepperman ML. Double-blind study of the reversal of midazolam-induced sedation in the intensive care unit with flumazenil (Ro 15-1788): effect on weaning from ventilation. Anaesth Intensive Care. 1990 Feb;18(1):38-44. doi: 10.1177/0310057X9001800107.'}, {'pmid': '26096314', 'type': 'BACKGROUND', 'citation': 'Penninga EI, Graudal N, Ladekarl MB, Jurgens G. Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication--A Systematic Review with Meta-Analyses of Randomised Trials. Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):37-44. doi: 10.1111/bcpt.12434. Epub 2015 Jul 28.'}, {'pmid': '22766408', 'type': 'BACKGROUND', 'citation': "Kreshak AA, Cantrell FL, Clark RF, Tomaszewski CA. 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Continuous flumazenil infusion in preventing complications arising from severe benzodiazepine intoxication. Am J Emerg Med. 1998 May;16(3):238-41. doi: 10.1016/s0735-6757(98)90091-2.'}, {'type': 'BACKGROUND', 'citation': 'Flumazenil [package insert]. San Francisco, CA, Genentech Inc, 2010'}, {'pmid': '19915454', 'type': 'BACKGROUND', 'citation': 'Devlin JW, Roberts RJ, Fong JJ, Skrobik Y, Riker RR, Hill NS, Robbins T, Garpestad E. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010 Feb;38(2):419-27. doi: 10.1097/CCM.0b013e3181b9e302.'}]}, 'descriptionModule': {'briefSummary': 'Delirium within the intensive care unit (ICU) is associated with poor outcomes such as increased mortality, ICU and hospital length of stay (LOS), and time on mechanical ventilation. Benzodiazepine (BZD) exposure is an independent risk factor for development of delirium. Reversal of hypoactive delirium represents a potential opportunity for reducing duration of delirium and subsequent complications.\n\nThis is a single-center randomized, double-blind, placebo-controlled study of critically ill adult patients with benzodiazepine-associated hypoactive delirium. The hypothesis is that flumazenil continuous infusion may reverse hypoactive delirium associated with BZD exposure and thereby reduce duration of delirium and ICU LOS.', 'detailedDescription': 'Benzodiazepines are commonly used for discomfort, anxiety, agitation, and alcohol withdrawal syndrome (AWS) in the ICU. End organ dysfunction and extended exposure can increase the risk of complications associated with BZDs, which include increased ICU LOS, time on mechanical ventilation, and mortality.\n\nFlumazenil as a 1, 4-imidazobenzodiazepine is a competitive antagonist for the benzodiazepine binding site with weak intrinsic or partial agonistic activity on the GABA receptor. Multiple studies have confirmed the safety and effectiveness of flumazenil for the reversal of sedation. Pilot studies have demonstrated safe reversal of over-sedation and statistically significant improvements in patient cooperation and time to extubation. The current standard for suspected BZD-associated hypoactive delirium is cessation of benzodiazepine administration and supportive care.\n\nThe role of continuous infusion flumazenil for rapid and sustained reversal of hypoactive delirium in the ICU has not been evaluated prospectively and therefore remains poorly defined.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* critically ill adults\n* RASS score of -3 to 0 after receiving benzodiazepine therapy\n* CAM-ICU positive\n* no benzodiazepine therapy within the previous 12 hours\n\nExclusion Criteria:\n\n1. contraindications to flumazenil including hypersensitivity\n2. receipt of benzodiazepines for control of potentially life-threatening conditions (e.g., control of intracranial pressure or status epilepticus)\n3. active seizure disorder or on current anti-convulsant therapy for history of seizure disorder. Seizures secondary to alcohol withdrawal will NOT be excluded.\n4. history of traumatic brain injury complicated by seizures\n5. acute episode (within prior 30 days) of severe traumatic brain injury\n6. history of structural lesion (e.g. subarachnoid hemorrhage, cerebrovascular accident, intra-parenchymal hemorrhage) complicated by seizures\n7. acute episode (within prior 14 days) of structural lesion (e.g. subarachnoid hemorrhage, cerebrovascular accident, intra-parenchymal hemorrhage)\n8. brain tumor complicated by seizure\n9. history of anoxic brain injury\n10. third-degree burn with total body surface area (TBSA) burn greater than 20%\n11. chronic benzodiazepine (clonazepam:lorazepam:diazepam approximately 4:8:40 mg per day) for 7 consecutive days with no taper\n12. chronic delirium that is attributable to other causes\n13. anticipated to transfer to lower level of care within 24 hours\n14. admitted for polysubstance overdose as determined by initial drug toxicity screening\n15. recent exposure (prior 7 days) to pro-convulsant medications (identified via medication list, medication reconciliation performed by PI/pharmacy medication reconciliation team, or urine drug screening)\n16. children, incarcerated individuals, and pregnant women\n17. unable to provide consent and the legally authorized representative is unable to provide consent'}, 'identificationModule': {'nctId': 'NCT02899156', 'acronym': 'FLYP', 'briefTitle': 'Flumazenil for Hypoactive Delirium Secondary to Benzodiazepine Exposure', 'organization': {'class': 'OTHER', 'fullName': 'University of California, Davis'}, 'officialTitle': 'Effect of Flumazenil on Hypoactive Delirium in the ICU: A Double-Blind, Placebo-Controlled Pilot Study', 'orgStudyIdInfo': {'id': '837421'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Flumazenil Infusion', 'description': 'The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.', 'interventionNames': ['Drug: Flumazenil']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo Infusion', 'description': 'The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Flumazenil', 'type': 'DRUG', 'otherNames': ['Romazicon'], 'armGroupLabels': ['Flumazenil Infusion']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '0.9% normal saline', 'armGroupLabels': ['Placebo Infusion']}]}, 'contactsLocationsModule': {'locations': [{'zip': '95817', 'city': 'Sacramento', 'state': 'California', 'country': 'United States', 'facility': 'UC Davis Medical Center', 'geoPoint': {'lat': 38.58157, 'lon': -121.4944}}], 'overallOfficials': [{'name': 'Kendra J Schomer, PharmD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of California, Davis'}, {'name': 'Jeremiah J Duby, PharmD, BCPS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of California, Davis'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of California, Davis', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}