Ignite Creation Date:
2025-12-24 @ 11:37 PM
Ignite Modification Date:
2025-12-25 @ 9:27 PM
Study NCT ID:
NCT01431456
Status:
COMPLETED
Last Update Posted:
2018-06-07
First Post:
2011-09-07
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D054556', 'term': 'Venous Thromboembolism'}], 'ancestors': [{'id': 'D013923', 'term': 'Thromboembolism'}, {'id': 'D016769', 'term': 'Embolism and Thrombosis'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069604', 'term': 'Dabigatran'}, {'id': 'D000069552', 'term': 'Rivaroxaban'}, {'id': 'D017762', 'term': 'Nadroparin'}], 'ancestors': [{'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D001562', 'term': 'Benzimidazoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D013876', 'term': 'Thiophenes'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D009025', 'term': 'Morpholines'}, {'id': 'D010078', 'term': 'Oxazines'}, {'id': 'D006495', 'term': 'Heparin, Low-Molecular-Weight'}, {'id': 'D006493', 'term': 'Heparin'}, {'id': 'D006025', 'term': 'Glycosaminoglycans'}, {'id': 'D011134', 'term': 'Polysaccharides'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['INVESTIGATOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 148}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-06', 'completionDateStruct': {'date': '2014-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-06-05', 'studyFirstSubmitDate': '2011-09-07', 'studyFirstSubmitQcDate': '2011-09-08', 'lastUpdatePostDateStruct': {'date': '2018-06-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2011-09-09', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The primary safety outcome is the incidence of bleeding events occurring during the study period of 135 days (including follow-up). Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines', 'timeFrame': '135 days', 'description': 'Major and clinically relevant non-major bleeding'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Prevention', 'venous thromboembolism after knee arthroplasty'], 'conditions': ['Venous Thromboembolism']}, 'referencesModule': {'references': [{'pmid': '33462096', 'type': 'DERIVED', 'citation': 'van der Veen L, Segers M, van Raay JJ, Gerritsma-Bleeker CL, Brouwer RW, Veeger NJ, van Hulst M. Bleeding complications of thromboprophylaxis with dabigatran, nadroparin or rivaroxaban for 6 weeks after total knee arthroplasty surgery: a randomised pilot study. BMJ Open. 2021 Jan 18;11(1):e040336. doi: 10.1136/bmjopen-2020-040336.'}, {'pmid': '23355673', 'type': 'DERIVED', 'citation': 'Veen Lv, van Raay JJ, Gerritsma-Bleeker CL, Veeger NJ, Hulst Mv. Direct treatment comparison of DAbigatran and RIvaroxaban versus NAdroparin in the prevention of venous thromboembolism after total knee arthroplasty surgery: design of a randomised pilot study (DARINA). BMJ Open. 2013 Jan 24;3(1):e002218. doi: 10.1136/bmjopen-2012-002218.'}]}, 'descriptionModule': {'briefSummary': "Rationale:\n\nAfter total knee arthroplasty (TKA) surgery, patients are at risk to develop venous thromboembolism (VTE) or deep venous thrombosis (DVT) potentially resulting in a fatal pulmonary embolism (PE). Two novel agents, dabigatran and rivaroxaban, recently gained market authorisation for prevention of venous thromboembolism after knee arthroplasty.\n\nHowever, there are no clinical trials with dabigatran and/or rivaroxaban and the comparator nadroparin.\n\nNadroparin is used in the most Dutch departments of orthopaedic surgery after total knee arthroplasty. Also safety of the new oral agents with long term use of 42 days is not available for total knee arthroplasty.\n\nOur aim is to compare the long term use of dabigatran and rivaroxaban versus nadroparin on safety after total knee arthroplasty (TKA) in a clinical explorative pilot study by observing the incidence of major bleeding and clinical relevant non-major bleeding using a standardized model of bleeding definitions.\n\nObjective:\n\nThe primary objective of this study is to compare the clinical safety with long term use of the oral once daily unmonitored thrombin inhibitors dabigatran and rivaroxaban versus subcutaneous administered nadroparin by observing the incidence of major bleeding and clinical relevant non-major bleeding in patients after knee arthroplasty surgery.\n\nThe secondary objectives of this study are effectivity of the agents, compliance, hospital stay, re-hospitalisation, outpatient clinic visits and interventions following complications. Additionally, coagulation monitoring, knee flexion range of motion, Knee injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score (KSS) and relationship between health statuses and surgery parameters will be evaluated.\n\nStudy design:\n\nThe study is designed as non-inferiority randomized open label controlled pilot study. A total of 150 patients will be included, 50 patients in each treatment group (dabigatran, rivaroxaban and nadroparin).\n\nStudy population:\n\nPatients ≥ 18 years and weighing more than 40 kg, participate in the 'joint care program' for primary elective total knee arthroplasty and want to provide signed informed consent are eligible for the study.\n\nIntervention:\n\nPatients receive subcutaneously nadroparin or oral rivaroxaban or oral dabigatran after knee replacement surgery.\n\nMain study parameters/endpoints:\n\nThe primary safety outcome is the incidence of bleeding events occurring during the study period of 135 days (including follow-up). Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '110 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\nPatients \\> 18 years and weighing more than 40 kg who are scheduled for primary elective total knee arthroplasty according to the 'joint care program' and want to provided signed informed consent are eligible for the study.\n\nExclusion Criteria:\n\n* a known inherited or acquired clinically significant active high risk of bleeding or bleeding disorder;\n* major surgery, trauma, uncontrolled severe arterial hypertension, or myocardial infarction within the last 3 months;\n* history of acute intracranial disease or hemorrhagic stroke;\n* gastrointestinal or urogenital bleeding or ulcer disease within the last 6 months;\n* cirrhotic patients with moderate hepatic impairment (aspartate or alanine aminotransferase (AST, ALT) levels higher than 2x the upper limit of the normal range (ULN) within the last month);\n* severe renal insufficiency (creatinine clearance \\< 30 mL/min);\n* treatment with anticoagulants during study drug treatment;\n* active malignant disease;\n* pregnancy or breastfeeding;\n* and unable to give informed consent."}, 'identificationModule': {'nctId': 'NCT01431456', 'acronym': 'DARINA', 'briefTitle': 'Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery', 'organization': {'class': 'OTHER', 'fullName': 'Martini Hospital Groningen'}, 'officialTitle': 'A Randomized Pilot Study Comparing the Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery', 'orgStudyIdInfo': {'id': 'DARINA'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Dabigatran', 'description': 'Dabigatran', 'interventionNames': ['Drug: Dabigatran']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Rivaroxaban', 'description': 'Rivaroxaban', 'interventionNames': ['Drug: Rivaroxaban']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Nadroparin', 'description': 'Nadroparin', 'interventionNames': ['Drug: Nadroparin']}], 'interventions': [{'name': 'Dabigatran', 'type': 'DRUG', 'description': 'Dabigatran', 'armGroupLabels': ['Dabigatran']}, {'name': 'Rivaroxaban', 'type': 'DRUG', 'description': 'Rivaroxaban', 'armGroupLabels': ['Rivaroxaban']}, {'name': 'Nadroparin', 'type': 'DRUG', 'description': 'Nadroparin', 'armGroupLabels': ['Nadroparin']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Groningen', 'country': 'Netherlands', 'facility': 'Martini Ziekenhuis', 'geoPoint': {'lat': 53.21917, 'lon': 6.56667}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Martini Hospital Groningen', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Hospital Pharmacist', 'investigatorFullName': 'Marinus van Hulst', 'investigatorAffiliation': 'Martini Hospital Groningen'}}}}