Ignite Creation Date:
2025-12-24 @ 11:36 PM
Ignite Modification Date:
2026-01-01 @ 2:25 PM
Study NCT ID:
NCT00357656
Status:
COMPLETED
Last Update Posted:
2021-05-19
First Post:
2006-07-25
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Phase 3/4 Study of a Recombinant Protein-Free Factor VIII (rAHF-PFM): Comparison of Continuous Infusion Versus Intermittent Bolus Infusion in Hemophilia A Subjects Undergoing Major Orthopedic Surgery
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Israel', 'United Kingdom']}, 'conditionBrowseModule': {'meshes': [{'id': 'D006467', 'term': 'Hemophilia A'}], 'ancestors': [{'id': 'D025861', 'term': 'Blood Coagulation Disorders, Inherited'}, {'id': 'D001778', 'term': 'Blood Coagulation Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D020147', 'term': 'Coagulation Protein Disorders'}, {'id': 'D006474', 'term': 'Hemorrhagic Disorders'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'ClinicalTransparency@shire.com', 'phone': '+1 866 842 5335', 'title': 'Study Director', 'organization': 'Shire'}, 'certainAgreement': {'otherDetails': 'Agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication. Baxalta requires a review of results communication (e.g. for confidential information) \\>= 30 days prior to submission. Baxalta may request an additional delay of \\<=120 days (e.g. for intellectual property protection).', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Throughout the study period. Overall: 9 years and 6 months. Per participant: 9-26 weeks.', 'eventGroups': [{'id': 'EG000', 'title': 'Bolus Infusion', 'description': 'All participants who were randomized to receive bolus infusion (BI) of ADVATE (rAHF-PFM). At total of 31 participants were randomized and received at least one ADVATE (rAHF-PFM) dose.', 'otherNumAtRisk': 31, 'otherNumAffected': 22, 'seriousNumAtRisk': 31, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'Continuous Infusion', 'description': 'All participants who were randomized to receive continuous infusion (CI) of ADVATE (rAHF-PFM). At total of 32 participants were randomized and received at least one ADVATE (rAHF-PFM) dose.', 'otherNumAtRisk': 32, 'otherNumAffected': 20, 'seriousNumAtRisk': 32, 'seriousNumAffected': 6}, {'id': 'EG002', 'title': 'Not Assigned Participants', 'description': 'All participants who were not assigned to either bolus infusion or continuous infusion but received at least one ADVATE (rAHF-PFM) dose during pharmacokinetic evaluation. A total of 9 participants received only the pharmacokinetic infusion and were not randomized.', 'otherNumAtRisk': 9, 'otherNumAffected': 2, 'seriousNumAtRisk': 9, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Procedural pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 16, 'numAffected': 16}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Anemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Thrombocytosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Tachycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Tooth Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Adenoma benign', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Erythema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Muscle Hemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Influenza', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Anaemia postoperative', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Haemarthrosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}], 'seriousEvents': [{'term': 'Factor VIII inhibition', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Multi-organ failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Febrile infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Pseudomembranous colitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Hemarthrosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Joint swelling', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}, {'term': 'Muscle hemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 18.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '28', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '22', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}, {'value': '4', 'groupId': 'OG004'}, {'value': '23', 'groupId': 'OG005'}, {'value': '1', 'groupId': 'OG006'}, {'value': '2', 'groupId': 'OG007'}]}], 'groups': [{'id': 'OG000', 'title': 'Bolus Infusion', 'description': 'Bolus infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG001', 'title': 'Continuous Infusion', 'description': 'Continuous infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG002', 'title': 'BI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by bolus infusion'}, {'id': 'OG003', 'title': 'BI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by bolus infusion'}, {'id': 'OG004', 'title': 'BI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by bolus infusion'}, {'id': 'OG005', 'title': 'CI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by continuous infusion'}, {'id': 'OG006', 'title': 'CI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by continuous infusion'}, {'id': 'OG007', 'title': 'CI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by continuous infusion'}], 'classes': [{'categories': [{'measurements': [{'value': '3.632', 'spread': '0.971', 'groupId': 'OG000'}, {'value': '3.383', 'spread': '0.632', 'groupId': 'OG001'}, {'value': '3.718', 'spread': '0.978', 'groupId': 'OG002'}, {'value': '2.855', 'spread': '1.732', 'groupId': 'OG003'}, {'value': '3.548', 'spread': '0.577', 'groupId': 'OG004'}, {'value': '3.345', 'spread': '0.616', 'groupId': 'OG005'}, {'value': '3.400', 'spread': 'NA', 'comment': 'Stratum B for continuous infusion has only one subject with available data, therefore standard deviation is not available.', 'groupId': 'OG006'}, {'value': '3.820', 'spread': '1.103', 'groupId': 'OG007'}]}]}], 'analyses': [{'pValue': '0.001', 'groupIds': ['OG000', 'OG001', 'OG002', 'OG003', 'OG004', 'OG005', 'OG006', 'OG007'], 'paramType': 'Mean ratio CI/BI', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.924', 'ciLowerLimit': '0.816', 'ciUpperLimit': '1.046', 'pValueComment': 'one-sided p-value against the null hypothesis of ration \\>=200%', 'groupDescription': 'The main analysis used a point estimate and a two-sided 95% confidence interval for ratio of the primary outcome measure of CI over BI combined over the three strata: stratum A: unilateral knee replacement, stratum B: hip surgery, stratum C: shoulder/elbow/ankle/knee (except knee replacement) surgery.', 'statisticalMethod': 'Hypothesis test', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE_LEGACY', 'nonInferiorityComment': 'Non-inferiority by the 200% margin of non-inferiority was demonstrated if the upper confidence limit of a 95% 2-sided confidence interval for the ratio of means did not exceed 200%.'}], 'paramType': 'MEAN', 'timeFrame': 'During the first postoperative 24 hours every 8 hours ± 30 minutes the drainage fluid was to be recorded..', 'description': 'Drainage fluid volume was to be measured cumulatively and recorded every 8 hours ± 30 minutes during the first 24 hours following surgery. Unit of measure: Tera per Liter is the PRBC concentration in 10\\^12 units per 1 liter of drainage fluid.', 'unitOfMeasure': 'Tera per Liter', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours including hematocrit results for these drainage fluids. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.'}, {'type': 'SECONDARY', 'title': 'Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '29', 'groupId': 'OG001'}, {'value': '24', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}, {'value': '5', 'groupId': 'OG004'}, {'value': '24', 'groupId': 'OG005'}, {'value': '2', 'groupId': 'OG006'}, {'value': '3', 'groupId': 'OG007'}]}], 'groups': [{'id': 'OG000', 'title': 'Bolus Infusion', 'description': 'Bolus infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG001', 'title': 'Contiuous Infusion', 'description': 'Continuous infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG002', 'title': 'BI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by bolus infusion'}, {'id': 'OG003', 'title': 'BI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by bolus infusion'}, {'id': 'OG004', 'title': 'BI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by bolus infusion'}, {'id': 'OG005', 'title': 'CI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by continuous infusion'}, {'id': 'OG006', 'title': 'CI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by continuous infusion'}, {'id': 'OG007', 'title': 'CI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by continuous infusion'}], 'classes': [{'categories': [{'measurements': [{'value': '709.28', 'spread': '150.103', 'groupId': 'OG000'}, {'value': '811.11', 'spread': '79.511', 'groupId': 'OG001'}, {'value': '724.48', 'spread': '66.367', 'groupId': 'OG002'}, {'value': '265', 'spread': '49.497', 'groupId': 'OG003'}, {'value': '814.03', 'spread': '171.019', 'groupId': 'OG004'}, {'value': '819.22', 'spread': '66.992', 'groupId': 'OG005'}, {'value': '713.49', 'spread': '0', 'groupId': 'OG006'}, {'value': '811.25', 'spread': '163.027', 'groupId': 'OG007'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'During the first 24 postoperative hours blood loss was measured every 8 hours ± 30 minutes', 'description': 'Drainage fluid volume was to be measured cumulatively and recorded every 8 hours ± 30 minutes during the first 24 hours following surgery. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject 1) for the intraoperative procedure (defined as the time period from incision to application of compressive dressing and release of tourniquet, if applicable), 2) for the first 24 hours postoperatively, and 3) for the postoperative period until drain removal, if drainage continued beyond 24 hours. Units: Milliliter of blood', 'unitOfMeasure': 'Milliliter', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.'}, {'type': 'SECONDARY', 'title': 'Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}, {'value': '23', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}, {'value': '5', 'groupId': 'OG004'}, {'value': '23', 'groupId': 'OG005'}, {'value': '2', 'groupId': 'OG006'}, {'value': '3', 'groupId': 'OG007'}]}], 'groups': [{'id': 'OG000', 'title': 'Bolus Infusion', 'description': 'Bolus infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG001', 'title': 'Continuous Infusion', 'description': 'Continuous infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG002', 'title': 'BI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by bolus infusion'}, {'id': 'OG003', 'title': 'BI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by bolus infusion'}, {'id': 'OG004', 'title': 'BI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by bolus infusion'}, {'id': 'OG005', 'title': 'CI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by continuous infusion'}, {'id': 'OG006', 'title': 'CI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by continuous infusion'}, {'id': 'OG007', 'title': 'CI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by continuous infusion'}], 'classes': [{'categories': [{'measurements': [{'value': '766.73', 'spread': '182.463', 'groupId': 'OG000'}, {'value': '929.49', 'spread': '167.662', 'groupId': 'OG001'}, {'value': '752.91', 'spread': '42.343', 'groupId': 'OG002'}, {'value': '341.5', 'spread': '135.075', 'groupId': 'OG003'}, {'value': '1000.37', 'spread': '259.239', 'groupId': 'OG004'}, {'value': '899.83', 'spread': '45.459', 'groupId': 'OG005'}, {'value': '921.1', 'spread': '42.906', 'groupId': 'OG006'}, {'value': '1162.48', 'spread': '514.033', 'groupId': 'OG007'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'From end of surgery (application of compressive dressing and release of tourniquet, if applicable) until drain removal (up to postoperative day 7).', 'description': 'The total blood loss for the postoperative period (from end of surgery until drain removal) was adjusted for the expected blood loss by applying a log-transformation of the blood loss data. The drainage volume was measured every 8 hours +/- 30 minutes during the first 24 hours. If the drainage continued beyond 24 hours, the PRBC volume and hemoglobin was to be measured cumulatively every 24 hours or whenever the drainage bottle was emptied and at the time of drain removal. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject for the first 24 hours postoperatively, and for the postoperative period until drain removal, if drainage continued beyond 24 hours. Units: Milliliter of blood', 'unitOfMeasure': 'Milliliter', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours including hematocrit results for these drainage fluids. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.'}, {'type': 'SECONDARY', 'title': 'Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '29', 'groupId': 'OG001'}, {'value': '24', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}, {'value': '5', 'groupId': 'OG004'}, {'value': '24', 'groupId': 'OG005'}, {'value': '2', 'groupId': 'OG006'}, {'value': '3', 'groupId': 'OG007'}]}], 'groups': [{'id': 'OG000', 'title': 'Bolus Infusion', 'description': 'Bolus infusion of rAHF-PFM'}, {'id': 'OG001', 'title': 'Continuous Infusion', 'description': 'Continuous infusion of rAHF-PFM'}, {'id': 'OG002', 'title': 'BI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by bolus infusion'}, {'id': 'OG003', 'title': 'BI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by bolus infusion'}, {'id': 'OG004', 'title': 'BI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by bolus infusion'}, {'id': 'OG005', 'title': 'CI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by continuous infusion'}, {'id': 'OG006', 'title': 'CI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by continuous infusion'}, {'id': 'OG007', 'title': 'CI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by continuous infusion'}], 'classes': [{'categories': [{'measurements': [{'value': '0.10', 'spread': '0.301', 'groupId': 'OG000'}, {'value': '0.03', 'spread': '0.186', 'groupId': 'OG001'}, {'value': '0.08', 'spread': '0.282', 'groupId': 'OG002'}, {'value': '0.50', 'spread': '0.707', 'groupId': 'OG003'}, {'value': '0.00', 'spread': '0.000', 'groupId': 'OG004'}, {'value': '0.00', 'spread': '0.000', 'groupId': 'OG005'}, {'value': '0.50', 'spread': '0.707', 'groupId': 'OG006'}, {'value': '0.00', 'spread': '0.000', 'groupId': 'OG007'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Through Postoperative Day 7', 'description': 'To simplify the results below: Bleeding episodes were reported for 4 subjects (3 subjects on bolus infusion: 2 in Stratum A and 1 in Stratum B, and 1 subject on continuous infusion/Stratum B). The 4 subjects had 1 bleeding episode each. No bleeding episodes were reported for Stratum C.', 'unitOfMeasure': 'Bleeding Episodes', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours including hematocrit results for these drainage fluids. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.'}, {'type': 'SECONDARY', 'title': 'Number of Units of Packed Red Blood Cells Transfused', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '29', 'groupId': 'OG001'}, {'value': '24', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}, {'value': '5', 'groupId': 'OG004'}, {'value': '24', 'groupId': 'OG005'}, {'value': '2', 'groupId': 'OG006'}, {'value': '3', 'groupId': 'OG007'}]}], 'groups': [{'id': 'OG000', 'title': 'Bolus Infusion', 'description': 'Bolus infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG001', 'title': 'Continuous Infusion', 'description': 'Continuous infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG002', 'title': 'BI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by bolus infusion'}, {'id': 'OG003', 'title': 'BI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by bolus infusion'}, {'id': 'OG004', 'title': 'BI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by bolus infusion'}, {'id': 'OG005', 'title': 'CI Stratum A', 'description': 'Participants who underwent unilateral knee replacement and were treated by continuous infusion'}, {'id': 'OG006', 'title': 'CI Stratum B', 'description': 'Participants who underwent hip surgery and were treated by continuous infusion'}, {'id': 'OG007', 'title': 'CI Stratum C', 'description': 'Participants who underwent shoulder/elbow/ankle/knee (except knee replacement) surgery and were treated by continuous infusion'}], 'classes': [{'categories': [{'measurements': [{'value': '0.9', 'spread': '1.2', 'groupId': 'OG000'}, {'value': '1.3', 'spread': '1.4', 'groupId': 'OG001'}, {'value': '1.0', 'spread': '1.3', 'groupId': 'OG002'}, {'value': '1.5', 'spread': '2.1', 'groupId': 'OG003'}, {'value': '0.2', 'spread': '0.4', 'groupId': 'OG004'}, {'value': '1.2', 'spread': '1.3', 'groupId': 'OG005'}, {'value': '3.5', 'spread': '2.1', 'groupId': 'OG006'}, {'value': '0.7', 'spread': '1.2', 'groupId': 'OG007'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'During the first postoperative 24 hours', 'unitOfMeasure': 'PRBC Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours including hematocrit results for these drainage fluids. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.'}, {'type': 'SECONDARY', 'title': 'Number of Adverse Events Related to the Administration of the Study Product.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}, {'value': '72', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Bolus Infusion', 'description': 'Bolus infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG001', 'title': 'Continuous Infusion', 'description': 'Continuous infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG002', 'title': 'Safety Analysis Set', 'description': 'All participants treated with at least one ADVATE (rAHF-PFM) dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}, {'value': '14', 'groupId': 'OG002'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From first study drug exposure until study completion/discontinuation (approximately 9-26 weeks per subject)', 'description': 'All AEs from the first study drug exposure until the study completion/discontinuation date were to be recorded. Each AE was to be evaluated by the investigator for causal relationship (i.e., unrelated, possibly related or probably related) to the study product.', 'unitOfMeasure': 'Adverse Events', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants in the Safety Analysis Set treated with at least one ADVATE infusion.'}, {'type': 'SECONDARY', 'title': 'Incidence of Factor VIII Inhibitory Antibody (≥0.4 Bethesda Units Using the Nijmegen Modification of the Bethesda Assay Formation)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}, {'value': '72', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Bolus Infusion', 'description': 'Bolus infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG001', 'title': 'Continuous Infusion', 'description': 'Continuous infusion of ADVATE (rAHF-PFM)'}, {'id': 'OG002', 'title': 'Safety Analysis Set', 'description': 'All participants treated with at least one ADVATE (rAHF-PFM) dose'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}, {'value': '4', 'groupId': 'OG002'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Throughout the study period of approximately 9-26 weeks per participant', 'description': 'Number of participants that developed Factor VIII inhibitory antibody during the study.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants in the Safety Analysis Set treated with at least one ADVATE infusion.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Bolus Infusion', 'description': 'Bolus infusion of ADVATE (rAHF-PFM)'}, {'id': 'FG001', 'title': 'Continuous Infusion', 'description': 'Continuous infusion of ADVATE (rAHF-PFM)'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '31'}, {'groupId': 'FG001', 'numSubjects': '32'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '31'}, {'groupId': 'FG001', 'numSubjects': '29'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Other, No surgery performed', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '3'}]}]}], 'recruitmentDetails': 'Enrollment was conducted at 22 clinical sites in 12 countries (US, Austria, Norway, France, Portugal, Netherlands, Spain, Russia, Romania, Hungary, Italy, Poland). Of 85 participants enrolled, 72 participants participated in a PK study in the preoperative period; 63 participants were then randomized to treatment by continuous or bolus infusion.', 'preAssignmentDetails': 'Of 85 participants enrolled,15 were screen failures (2 after PK), 4 discontinued on the basis of the PK study in the preoperative period, 1 died, 1 was discontinued by physician decision (imprisonment), and 1 was discontinued per sponsor decision. Eventually, 63 participants were randomized to treatment by continuous (n=32) or bolus infusion (n=31)'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'BG000'}, {'value': '32', 'groupId': 'BG001'}, {'value': '63', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Bolus Infusion', 'description': 'Bolus infusion of ADVATE (rAHF-PFM)'}, {'id': 'BG001', 'title': 'Continuous Infusion', 'description': 'Continuous infusion of ADVATE (rAHF-PFM)'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '31', 'groupId': 'BG000'}, {'value': '32', 'groupId': 'BG001'}, {'value': '63', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '38.6', 'spread': '9.76', 'groupId': 'BG000'}, {'value': '39.0', 'spread': '11.52', 'groupId': 'BG001'}, {'value': '38.8', 'spread': '10.61', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '31', 'groupId': 'BG000'}, {'value': '32', 'groupId': 'BG001'}, {'value': '63', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 85}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2006-05-29', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-04', 'completionDateStruct': {'date': '2015-12-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-04-28', 'studyFirstSubmitDate': '2006-07-25', 'resultsFirstSubmitDate': '2017-01-11', 'studyFirstSubmitQcDate': '2006-07-26', 'lastUpdatePostDateStruct': {'date': '2021-05-19', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-04-12', 'studyFirstPostDateStruct': {'date': '2006-07-27', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-05-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2015-10-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI)', 'timeFrame': 'During the first postoperative 24 hours every 8 hours ± 30 minutes the drainage fluid was to be recorded..', 'description': 'Drainage fluid volume was to be measured cumulatively and recorded every 8 hours ± 30 minutes during the first 24 hours following surgery. Unit of measure: Tera per Liter is the PRBC concentration in 10\\^12 units per 1 liter of drainage fluid.'}], 'secondaryOutcomes': [{'measure': 'Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon', 'timeFrame': 'During the first 24 postoperative hours blood loss was measured every 8 hours ± 30 minutes', 'description': 'Drainage fluid volume was to be measured cumulatively and recorded every 8 hours ± 30 minutes during the first 24 hours following surgery. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject 1) for the intraoperative procedure (defined as the time period from incision to application of compressive dressing and release of tourniquet, if applicable), 2) for the first 24 hours postoperatively, and 3) for the postoperative period until drain removal, if drainage continued beyond 24 hours. Units: Milliliter of blood'}, {'measure': 'Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon', 'timeFrame': 'From end of surgery (application of compressive dressing and release of tourniquet, if applicable) until drain removal (up to postoperative day 7).', 'description': 'The total blood loss for the postoperative period (from end of surgery until drain removal) was adjusted for the expected blood loss by applying a log-transformation of the blood loss data. The drainage volume was measured every 8 hours +/- 30 minutes during the first 24 hours. If the drainage continued beyond 24 hours, the PRBC volume and hemoglobin was to be measured cumulatively every 24 hours or whenever the drainage bottle was emptied and at the time of drain removal. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject for the first 24 hours postoperatively, and for the postoperative period until drain removal, if drainage continued beyond 24 hours. Units: Milliliter of blood'}, {'measure': 'Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion', 'timeFrame': 'Through Postoperative Day 7', 'description': 'To simplify the results below: Bleeding episodes were reported for 4 subjects (3 subjects on bolus infusion: 2 in Stratum A and 1 in Stratum B, and 1 subject on continuous infusion/Stratum B). The 4 subjects had 1 bleeding episode each. No bleeding episodes were reported for Stratum C.'}, {'measure': 'Number of Units of Packed Red Blood Cells Transfused', 'timeFrame': 'During the first postoperative 24 hours'}, {'measure': 'Number of Adverse Events Related to the Administration of the Study Product.', 'timeFrame': 'From first study drug exposure until study completion/discontinuation (approximately 9-26 weeks per subject)', 'description': 'All AEs from the first study drug exposure until the study completion/discontinuation date were to be recorded. Each AE was to be evaluated by the investigator for causal relationship (i.e., unrelated, possibly related or probably related) to the study product.'}, {'measure': 'Incidence of Factor VIII Inhibitory Antibody (≥0.4 Bethesda Units Using the Nijmegen Modification of the Bethesda Assay Formation)', 'timeFrame': 'Throughout the study period of approximately 9-26 weeks per participant', 'description': 'Number of participants that developed Factor VIII inhibitory antibody during the study.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Hemophilia A (severe or moderately severe)'], 'conditions': ['Hemophilia A']}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to compare the hemostatic efficacy and safety of continuous infusion versus intermittent bolus infusion in the peri- and post-operative setting, employing rAHF-PFM, a recombinant antihemophilic factor manufactured without added human or animal proteins, in previously treated patients with severe or moderately severe hemophilia A (baseline factor VIII level \\<= 2% of normal) who are undergoing unilateral major orthopedic surgery that requires drain placement. The total study period per subject (from consent to study completion) will vary from approximately 9 to 26 weeks and will involve clinical and laboratory assessments.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* The subject or the subject's legally authorized representative has provided signed informed consent.\n* The subject is within 18 to 70 years of age.\n* The subject has severe or moderately severe hemophilia A, defined by a baseline factor VIII level \\<= 2% of normal, as tested at screening. A subset of 15 subjects per group must have baseline factor VIII levels \\< 1% of normal.\n* The aPTT must be within the range of normal after administration of FVIII concentrate, as determined in the preoperative pharmacokinetic evaluation, or as documented in the medical history, if available.\n* The subject is scheduled to undergo an elective unilateral major orthopedic surgery that requires drain placement.\n* The subject was previously treated with factor VIII concentrate(s) for a minimum of at least 150 exposure days (as estimated by the investigator) prior to study entry.\n* Human immunodeficiency virus (HIV) positive subjects must be immunocompetent as determined with a CD4 count \\>= 200 cells/mm³ (CD4 count at screening), but HIV negative subjects with a CD4 count \\< 200 cells/mm³ qualify, if immunocompetency is documented.\n* The subject has a life expectancy of at least 28 days from the day of surgery.\n\nExclusion Criteria:\n\n* The subject has a detectable factor VIII inhibitor at screening, with a titer \\>= 0.4 BU (Nijmegen modification of the Bethesda assay) in the central laboratory.\n* The subject has a history of factor VIII inhibitors with a titer \\>= 0.4 BU (by Nijmegen assay) or \\>= 0.5 BU (by Bethesda assay) at any time prior to screening.\n* The subject is scheduled to undergo any other concurrent minor or major surgery during the course of the study. The placement of central venous lines and the performance of fine needle aspiration biopsies are permitted.\n* Excluding hemophilia-related physical impairments, the subject is assigned to NYHA class \\>= III according to the New York Heart Association (NYHA).\n* The subject has an abnormal renal function (serum creatinine \\> 1.5 mg/dL).\n* The subject has active hepatic disease (alanine aminotransferase \\[ALT\\] or aspartate aminotransferase \\[AST\\] levels \\> 5 times the upper limit of normal).\n* The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) \\> 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices.\n* The subject has clinical and/or laboratory evidence of abnormal hemostasis from causes other than hemophilia A (e.g., late-stage chronic liver disease, immune thrombocytopenia purpura).\n* The subject is currently receiving, or is scheduled to receive during the course of the study, an immunomodulating drug other than anti-retroviral chemotherapy (e.g., alpha-interferon, corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day).\n* The subject has a known hypersensitivity to mouse or hamster proteins.\n* The subject has received another investigational drug study within 30 days prior to screening and/or is scheduled to receive additional investigational drug during the course of the trial in the context of another investigational study.\n* The subject is identified by the investigator as being unable or unwilling to cooperate with study procedures."}, 'identificationModule': {'nctId': 'NCT00357656', 'briefTitle': 'Phase 3/4 Study of a Recombinant Protein-Free Factor VIII (rAHF-PFM): Comparison of Continuous Infusion Versus Intermittent Bolus Infusion in Hemophilia A Subjects Undergoing Major Orthopedic Surgery', 'organization': {'class': 'INDUSTRY', 'fullName': 'Takeda'}, 'officialTitle': 'Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method (rAHF PFM): A Phase 3/4, Prospective, Controlled, Randomized, Multi-Center Study to Compare the Efficacy and Safety of Continuous Infusion (CI) Versus Intermittent Bolus Infusion (BI) in Subjects With Severe or Moderately Severe Hemophilia A Undergoing Major Orthopedic Surgery', 'orgStudyIdInfo': {'id': '060402'}, 'secondaryIdInfos': [{'id': '2005-005697-71', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'BI', 'description': 'Bolus infusion of rAHF-PFM', 'interventionNames': ['Drug: Recombinant Protein-Free Factor VIII (rAHF-PFM)']}, {'type': 'EXPERIMENTAL', 'label': 'CI', 'description': 'Continuous infusion of rAHF-PFM', 'interventionNames': ['Drug: Recombinant Protein-Free Factor VIII (rAHF-PFM)']}], 'interventions': [{'name': 'Recombinant Protein-Free Factor VIII (rAHF-PFM)', 'type': 'DRUG', 'description': 'An initial loading dose will be administered intravenously over a period \\<= 5 minutes (maximum of infusion rate of 10 mL/minute) within 60 minutes prior to surgery dose in order to maintain a minimum target FVIII level of at least 80% of normal.\n\nCI will start prior to surgery as soon as the loading dose has been administered, at a rate calculated according to a formula provided by the sponsor.\n\nAll study product must be administered with a syringe pump running at an infusion rate according to the dosing regimen, but always \\>= 0.4 mL/h.', 'armGroupLabels': ['CI']}, {'name': 'Recombinant Protein-Free Factor VIII (rAHF-PFM)', 'type': 'DRUG', 'description': 'The treatment schedule for intermittent BI of rAHF-PFM will begin with the administration of the loading dose according to the dose recommendations provided by the sponsor. If required by the hemostatic challenge, additional boluses may be administered after a blood sample for FVIII determination has been drawn. All infusions of rAHF PFM will be given over a period \\<= 5 minutes (maximum infusion rate, 10 mL/min).', 'armGroupLabels': ['BI']}]}, 'contactsLocationsModule': {'locations': [{'zip': '90007', 'city': 'Los Angeles', 'state': 'California', 'country': 'United States', 'facility': 'Los Angeles Orthopaedic Hospital', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '20057', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'Georgetown University', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '60612', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Rush Presbyterian St. Lukes', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '40202', 'city': 'Louisville', 'state': 'Kentucky', 'country': 'United States', 'facility': 'James Graham Brown Cancer Center', 'geoPoint': {'lat': 38.25424, 'lon': -85.75941}}, {'zip': '70112-2699', 'city': 'New Orleans', 'state': 'Louisiana', 'country': 'United States', 'facility': 'Tulane University', 'geoPoint': {'lat': 29.95465, 'lon': -90.07507}}, {'zip': '21205', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins Medical Institutions', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Brigham and Women´s Hospital', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '44106-6010', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'University Hospitals of Cleveland', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': '17033', 'city': 'Hershey', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Penn State Milton S. 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