Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery (DARINA)
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.
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.
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).
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.
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.
|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 ]
|Study Start Date:||October 2011|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: Dabigatran||Drug: Dabigatran|
|Active Comparator: Rivaroxaban||Drug: Rivaroxaban|
|Active Comparator: Nadroparin||Drug: Nadroparin|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01431456
|Contact: Marinus van Hulst, PharmD PhD||+31 50 email@example.com|
|Martini Ziekenhuis||Not yet recruiting|
|Principal Investigator: Marinus van Hulst, PharmD PhD|