Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery (DARINA)
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Purpose
Rationale:
After 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.
However, there are no clinical trials with dabigatran and/or rivaroxaban and the comparator nadroparin.
Nadroparin 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.
Our 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.
Objective:
The 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.
The 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.
Study design:
The 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).
Study population:
Patients ≥ 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.
Intervention:
Patients receive subcutaneously nadroparin or oral rivaroxaban or oral dabigatran after knee replacement surgery.
Main study parameters/endpoints:
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Venous Thromboembolism |
Drug: Dabigatran Drug: Rivaroxaban Drug: Nadroparin |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Single Blind (Investigator) Primary Purpose: Prevention |
| Official Title: | A Randomized Pilot Study Comparing the Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery |
- 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 [ Time Frame: 135 days ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 150 |
| Study Start Date: | October 2011 |
| Estimated Primary Completion Date: | October 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: Dabigatran | Drug: Dabigatran |
| Active Comparator: Rivaroxaban | Drug: Rivaroxaban |
| Active Comparator: Nadroparin | Drug: Nadroparin |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients > 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.
Exclusion Criteria:
- a known inherited or acquired clinically significant active high risk of bleeding or bleeding disorder;
- major surgery, trauma, uncontrolled severe arterial hypertension, or myocardial infarction within the last 3 months;
- history of acute intracranial disease or hemorrhagic stroke;
- gastrointestinal or urogenital bleeding or ulcer disease within the last 6 months;
- 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);
- severe renal insufficiency (creatinine clearance < 30 mL/min);
- treatment with anticoagulants during study drug treatment;
- active malignant disease;
- pregnancy or breastfeeding;
- and unable to give informed consent.
Contacts and Locations| Contact: Marinus van Hulst, PharmD PhD | +31 50 5247381 | hulstr@mzh.nl |
| Netherlands | |
| Martini Ziekenhuis | Not yet recruiting |
| Groningen, Netherlands | |
| Principal Investigator: Marinus van Hulst, PharmD PhD | |
More Information
No publications provided
| Responsible Party: | Marinus van Hulst, Hospital Pharmacist, Martini Hospital Groningen |
| ClinicalTrials.gov Identifier: | NCT01431456 History of Changes |
| Other Study ID Numbers: | DARINA |
| Study First Received: | September 7, 2011 |
| Last Updated: | September 8, 2011 |
| Health Authority: | The Netherlands: CCMO, The Hague |
Keywords provided by Martini Hospital Groningen:
|
Prevention venous thromboembolism after knee arthroplasty |
Additional relevant MeSH terms:
|
Thromboembolism Venous Thromboembolism Venous Thrombosis Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Thrombosis Nadroparin |
Anticoagulants Hematologic Agents Therapeutic Uses Pharmacologic Actions Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Cardiovascular Agents |
ClinicalTrials.gov processed this record on May 16, 2013