Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery

Phase 3

Completed

• Conditions: Venous Thromboembolism
• Interventions: Drug: Nadroparin; Drug: Dabigatran; Drug: Rivaroxaban

• Registration Number: NCT01431456
• Lead Sponsor: Martini Hospital Groningen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-09-07
• Study First Submitted QC: 2011-09-08
• Study First Posted: 2011-09-09
• Study Start: 2013-09
• Primary Completion: 2014-10
• Study Completion: 2014-10
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-05
• Last Update Posted: 2018-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 148

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nadroparin	Nadroparin	Nadroparin
Dabigatran	Dabigatran	Dabigatran
Rivaroxaban	Rivaroxaban	Rivaroxaban

Primary Outcome Measures

Name	Time	Method
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	135 days	Major and clinically relevant non-major bleeding

Trial Locations

Locations (1)

Martini Ziekenhuis; 🇳🇱 Groningen, Netherlands