Ignite Creation Date:
2025-12-24 @ 10:30 PM
Ignite Modification Date:
2026-01-01 @ 6:26 PM
Study NCT ID:
NCT03064035
Status:
COMPLETED
Last Update Posted:
2023-09-14
First Post:
2017-02-16
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Fixed Versus Variable Dosing of 4-factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2023-02-09', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D006470', 'term': 'Hemorrhage'}], 'ancestors': [{'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Zachary.Stoecker@parknicollet.com', 'phone': '952-977-5520', 'title': 'Zachary Stoecker, PharmD', 'organization': 'Methodist Hospital'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': 'From enrollment through 7 days.', 'eventGroups': [{'id': 'EG000', 'title': 'Fixed Dose 4FPCC', 'description': "Incorporating a fixed dose of 1500 IU.\n\nIf the patient receiving the 1500 IU fixed dose remains in a bleeding state and the INR remains above goal, an additional 500 IU may be administered at the physician's discretion to minimize bleeding and attempt to achieve hemostasis.\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.", 'otherNumAtRisk': 34, 'deathsNumAtRisk': 34, 'otherNumAffected': 0, 'seriousNumAtRisk': 34, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Variable Dose 4FPCC', 'description': 'The FDA-approved variable dosing algorithm is as follows:\n\ninitial INR 2-3.9: 25 IU/kg (maximum dose 2500 IU), initial INR 4-6: 35 IU/kg (maximum dose 3500 IU), and initial INR \\>6: 50 IU/kg (maximum dose 5000 IU). The patient weight will be obtained using a scale and documented by the treating registered nurse\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.', 'otherNumAtRisk': 37, 'deathsNumAtRisk': 37, 'otherNumAffected': 0, 'seriousNumAtRisk': 37, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants Who Demonstrated Significant Reversal of INR Within 15 Minutes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'OG000'}, {'value': '37', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Fixed Dose 4FPCC', 'description': "Incorporating a fixed dose of 1500 IU.\n\nIf the patient receiving the 1500 IU fixed dose remains in a bleeding state and the INR remains above goal, an additional 500 IU may be administered at the physician's discretion to minimize bleeding and attempt to achieve hemostasis.\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department."}, {'id': 'OG001', 'title': 'Variable Dose 4FPCC', 'description': 'The FDA-approved variable dosing algorithm is as follows:\n\ninitial INR 2-3.9: 25 IU/kg (maximum dose 2500 IU), initial INR 4-6: 35 IU/kg (maximum dose 3500 IU), and initial INR \\>6: 50 IU/kg (maximum dose 5000 IU). The patient weight will be obtained using a scale and documented by the treating registered nurse\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.'}], 'classes': [{'categories': [{'measurements': [{'value': '21', 'groupId': 'OG000'}, {'value': '33', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '15 minutes', 'description': 'To evaluate whether fixed dose 4FPCC is acceptably comparable to variable dosing with respect to anticoagulation reversal, as defined by a targeted INR of ≤1.5', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With a Thromboembolic Event', 'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'OG000'}, {'value': '37', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Fixed Dose 4FPCC', 'description': "Incorporating a fixed dose of 1500 IU.\n\nIf the patient receiving the 1500 IU fixed dose remains in a bleeding state and the INR remains above goal, an additional 500 IU may be administered at the physician's discretion to minimize bleeding and attempt to achieve hemostasis.\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department."}, {'id': 'OG001', 'title': 'Variable Dose 4FPCC', 'description': 'The FDA-approved variable dosing algorithm is as follows:\n\ninitial INR 2-3.9: 25 IU/kg (maximum dose 2500 IU), initial INR 4-6: 35 IU/kg (maximum dose 3500 IU), and initial INR \\>6: 50 IU/kg (maximum dose 5000 IU). The patient weight will be obtained using a scale and documented by the treating registered nurse\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'up to 7 days post administration of 4FPCC', 'description': 'Study patients will be followed post-administration of 4FPCC for thromboembolic events such as deep vein thrombosis, pulmonary embolism, ischemic stroke or transient ischemic event, or myocardial infarction.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Total Cost of Dosing Strategy', 'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'OG000'}, {'value': '37', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Fixed Dose 4FPCC', 'description': "Incorporating a fixed dose of 1500 IU.\n\nIf the patient receiving the 1500 IU fixed dose remains in a bleeding state and the INR remains above goal, an additional 500 IU may be administered at the physician's discretion to minimize bleeding and attempt to achieve hemostasis.\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department."}, {'id': 'OG001', 'title': 'Variable Dose 4FPCC', 'description': 'The FDA-approved variable dosing algorithm is as follows:\n\ninitial INR 2-3.9: 25 IU/kg (maximum dose 2500 IU), initial INR 4-6: 35 IU/kg (maximum dose 3500 IU), and initial INR \\>6: 50 IU/kg (maximum dose 5000 IU). The patient weight will be obtained using a scale and documented by the treating registered nurse\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.'}], 'classes': [{'categories': [{'measurements': [{'value': '2524.56', 'groupId': 'OG000', 'lowerLimit': '2497.87', 'upperLimit': '2551.25'}, {'value': '3372.36', 'groupId': 'OG001', 'lowerLimit': '2643.36', 'upperLimit': '4101.36'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Hospital Stay, Up to 6 months', 'description': 'Cost outcomes will be assessed for all study patients and compared by dosing assignment. Cost of treatment was assessed based on the amount of 4FPCC doses administered during admission, using the study-contemporary rate of $1.57/unit', 'unitOfMeasure': 'dollars', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Fixed Dose 4FPCC', 'description': "Incorporating a fixed dose of 1500 IU.\n\nIf the patient receiving the 1500 IU fixed dose remains in a bleeding state and the INR remains above goal, an additional 500 IU may be administered at the physician's discretion to minimize bleeding and attempt to achieve hemostasis.\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department."}, {'id': 'FG001', 'title': 'Variable Dose 4FPCC', 'description': 'The FDA-approved variable dosing algorithm is as follows:\n\ninitial INR 2-3.9: 25 IU/kg (maximum dose 2500 IU), initial INR 4-6: 35 IU/kg (maximum dose 3500 IU), and initial INR \\>6: 50 IU/kg (maximum dose 5000 IU). The patient weight will be obtained using a scale and documented by the treating registered nurse\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'Randomized to fixed dosing', 'groupId': 'FG000', 'numSubjects': '39'}, {'comment': 'Randomized to variable dosing', 'groupId': 'FG001', 'numSubjects': '40'}]}, {'type': 'COMPLETED', 'achievements': [{'comment': 'Fixed dosing subjects used in analysis', 'groupId': 'FG000', 'numSubjects': '34'}, {'comment': 'Variable dosing subjects used in analysis', 'groupId': 'FG001', 'numSubjects': '37'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Did not receive allocated intervention', 'reasons': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'preAssignmentDetails': 'A total 192 patients who presented to the emergency department with emergent bleeding were screened for eligibility and 79 of these patients were enrolled. 107 did not meet inclusion criteria, 1 declined participation, and 5 were unable to be enrolled prior to administration of Kcentra.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'BG000'}, {'value': '37', 'groupId': 'BG001'}, {'value': '71', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Fixed Dose 4FPCC', 'description': "Incorporating a fixed dose of 1500 IU.\n\nIf the patient receiving the 1500 IU fixed dose remains in a bleeding state and the INR remains above goal, an additional 500 IU may be administered at the physician's discretion to minimize bleeding and attempt to achieve hemostasis.\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department."}, {'id': 'BG001', 'title': 'Variable Dose 4FPCC', 'description': 'The FDA-approved variable dosing algorithm is as follows:\n\ninitial INR 2-3.9: 25 IU/kg (maximum dose 2500 IU), initial INR 4-6: 35 IU/kg (maximum dose 3500 IU), and initial INR \\>6: 50 IU/kg (maximum dose 5000 IU). The patient weight will be obtained using a scale and documented by the treating registered nurse\n\n4-factor prothrombin complex concentrate (4FPCC): 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'BG000'}, {'value': '37', 'groupId': 'BG001'}, {'value': '71', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '74.5', 'groupId': 'BG000', 'lowerLimit': '62.5', 'upperLimit': '86.5'}, {'value': '76', 'groupId': 'BG001', 'lowerLimit': '67.5', 'upperLimit': '84.5'}, {'value': '76', 'groupId': 'BG002', 'lowerLimit': '65.5', 'upperLimit': '86.5'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'INTER_QUARTILE_RANGE', 'populationDescription': 'There are two different age ranges based on randomized groups - fixed and variable dosing'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'BG000'}, {'value': '37', 'groupId': 'BG001'}, {'value': '71', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '23', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '24', 'groupId': 'BG000'}, {'value': '24', 'groupId': 'BG001'}, {'value': '48', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'There are two different sex distributions for the two randomized groups - fixed and variable dosing'}, {'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': '34', 'groupId': 'BG000'}, {'value': '37', 'groupId': 'BG001'}, {'value': '71', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '34', 'groupId': 'BG000'}, {'value': '37', 'groupId': 'BG001'}, {'value': '71', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants', 'populationDescription': 'There are two different randomized groups - fixed and variable dosing'}], 'populationDescription': 'Patients were randomized to one of two arms - fixed or variable dosing'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2016-03-01', 'size': 499558, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_001.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2023-06-19T15:14', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'For adults on long-term warfarin therapy who present to the ED with emergent bleeding, or who are in need of urgent invasive surgical procedures: the exposure of interest will be fixed vs. variable dose 4FPCC, to which eligible patients will be randomly assigned in a 1:1 ratio.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 79}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-04-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-06', 'completionDateStruct': {'date': '2019-04-24', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-09-01', 'studyFirstSubmitDate': '2017-02-16', 'resultsFirstSubmitDate': '2023-01-12', 'studyFirstSubmitQcDate': '2017-02-21', 'lastUpdatePostDateStruct': {'date': '2023-09-14', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-06-19', 'studyFirstPostDateStruct': {'date': '2017-02-24', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-07-11', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-04-17', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants Who Demonstrated Significant Reversal of INR Within 15 Minutes', 'timeFrame': '15 minutes', 'description': 'To evaluate whether fixed dose 4FPCC is acceptably comparable to variable dosing with respect to anticoagulation reversal, as defined by a targeted INR of ≤1.5'}], 'secondaryOutcomes': [{'measure': 'Number of Participants With a Thromboembolic Event', 'timeFrame': 'up to 7 days post administration of 4FPCC', 'description': 'Study patients will be followed post-administration of 4FPCC for thromboembolic events such as deep vein thrombosis, pulmonary embolism, ischemic stroke or transient ischemic event, or myocardial infarction.'}, {'measure': 'Total Cost of Dosing Strategy', 'timeFrame': 'Hospital Stay, Up to 6 months', 'description': 'Cost outcomes will be assessed for all study patients and compared by dosing assignment. Cost of treatment was assessed based on the amount of 4FPCC doses administered during admission, using the study-contemporary rate of $1.57/unit'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Acute Bleeding on Long-Term Anticoagulation Therapy', 'Hemorrhage', 'Significant Bleeding in Patients With a Coagulopathy (Prolonged Thrombin Time)', 'Urgent Reversal of Vitamin K Antagonist (VKA) Anticoagulation']}, 'descriptionModule': {'briefSummary': "The goal of this study is to determine if a fixed dose of 4-factor prothrombin complex concentrate (4FPCC) is as effective as the current standard of care. 4FPCC is used to reverse the effects of warfarin when a patient has emergent bleeding. The investigators hope that this study will help doctors treat patients quicker in the future. In addition, it may be cheaper for patients and hospitals. This is the same medication the doctor would use to reverse warfarin's effects, but at a lower dose.\n\nHypothesis: A fixed dose of 4FPCC will be comparable to FDA-approved variable dosing for reversal of warfarin-induced anticoagulation (defined as an international normalized ratio \\[INR\\] ≤ 1.5) in patients with an INR ≥2 experiencing an emergent bleed or requiring emergent surgery.", 'detailedDescription': 'Warfarin is a common oral anticoagulant utilized in the United States for the treatment and prevention of thromboembolic events and conditions. Although effective, the major complication associated with warfarin is the risk of major bleeding events. Incidence of major bleeding events in long-term warfarin users is 1.5% to 5.2% per year, with mortality exceeding 13%. Among patients with an intracranial bleed, the mortality rate increases to 46%-55%. In these situations, it is imperative to reverse the pharmacologic effects of warfarin quickly in order to minimize bleeding and reduce the risk of death. Warfarin inhibits formation of vitamin K-dependent clotting factors II, VII, IX, X, and proteins C and S. An international normalized ratio (INR) is a commonly utilized laboratory test to measure the amount of anticoagulation provided by warfarin and is monitored throughout therapy. The INR is a standardized ratio utilizing prothrombin time to prevent variation between institutional laboratories. Prothrombin time is defined as the time required for plasma to clot after addition of clotting factor. A normal INR in a healthy adult can range from 0.8-1.2. The majority of patients on chronic warfarin therapy will have a target INR of 2-3.\n\nThe optimal dose of 4FPCC is currently unknown despite multiple studies evaluating different dosing regimens. The FDA-approved dosing is 25 to 50 IU factor IX per kilogram of body weight, depending on INR. It is dosed to a maximum of 100 kilograms of body weight. The FDA-approved variable dosing algorithm is as follows: initial INR 2-3.9: 25 IU/kg (maximum dose 2500 IU), initial INR 4-6: 35 IU/kg (maximum dose 3500 IU), and initial INR \\>6: 50 IU/kg (maximum dose 5000 IU). Exact doses of 4FPCC administered may vary slightly from the calculated doses as the amount of 4FPCC differs based on the vials utilized.\n\nBy incorporating a fixed dose of 1500 IU, presenting INR and body weight may not need to be determined prior to administration. This may allow for early administration and prevent delay for warfarin reversal in patients with emergent bleeding. This research may determine whether a fixed dose is effective for reversing warfarin to a target INR less than 1.5 compared to FDA-approved variable dosing. In addition, the lower fixed-dose will significantly reduce costs to the institution.\n\nHypothesis: A fixed dose of 4FPCC will be comparable to FDA-approved variable dosing for reversal of warfarin-induced anticoagulation (defined as an international normalized ratio \\[INR\\] ≤ 1.5) in patients with an INR ≥2 experiencing an emergent bleed or requiring emergent surgery.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '125 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Chronic anticoagulation with warfarin and initial INR ≥2\n* Emergent bleeding (i.e. intracranial hemorrhage, gastrointestinal hemorrhage, urgent invasive procedures, etc.) or urgent surgery requiring reversal of INR to ≤1.5\n\nExclusion Criteria:\n\n* Younger than 18 years of age\n* History of heparin-induced thrombocytopenia (HIT)\n* Patients without initial or post-administration INR readings\n* Patients with an initial INR \\<2\n* Pregnant patients\n* Prisoners'}, 'identificationModule': {'nctId': 'NCT03064035', 'acronym': 'kcentra', 'briefTitle': 'Fixed Versus Variable Dosing of 4-factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal', 'organization': {'class': 'OTHER', 'fullName': 'HealthPartners Institute'}, 'officialTitle': 'A Prospective, Randomized Study of Fixed Versus Variable Dosing of 4-factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal at a Large Tertiary Care Medical Center', 'orgStudyIdInfo': {'id': 'A16-732'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Fixed dose 4FPCC', 'description': "Incorporating a fixed dose of 1500 IU.\n\nIf the patient receiving the 1500 IU fixed dose remains in a bleeding state and the INR remains above goal, an additional 500 IU may be administered at the physician's discretion to minimize bleeding and attempt to achieve hemostasis.", 'interventionNames': ['Drug: 4-factor prothrombin complex concentrate (4FPCC)']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Variable dose 4FPCC', 'description': 'The FDA-approved variable dosing algorithm is as follows:\n\ninitial INR 2-3.9: 25 IU/kg (maximum dose 2500 IU), initial INR 4-6: 35 IU/kg (maximum dose 3500 IU), and initial INR \\>6: 50 IU/kg (maximum dose 5000 IU). The patient weight will be obtained using a scale and documented by the treating registered nurse', 'interventionNames': ['Drug: 4-factor prothrombin complex concentrate (4FPCC)']}], 'interventions': [{'name': '4-factor prothrombin complex concentrate (4FPCC)', 'type': 'DRUG', 'description': '4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.', 'armGroupLabels': ['Fixed dose 4FPCC', 'Variable dose 4FPCC']}]}, 'contactsLocationsModule': {'locations': [{'zip': '55101', 'city': 'Saint Paul', 'state': 'Minnesota', 'country': 'United States', 'facility': 'Regions Hospital', 'geoPoint': {'lat': 44.94441, 'lon': -93.09327}}], 'overallOfficials': [{'name': 'Zachary Stoecker, PharmD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Regions Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'HealthPartners Institute', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}