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

Sponsor

Martini Hospital Groningen (Other)

Overall Status

Completed

CT.gov ID

NCT01431456

Collaborator

(none)

148

Enrollment

Location

Arms

Actual Duration (Months)

11.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Venous Thromboembolism	Drug: Dabigatran Drug: Rivaroxaban Drug: Nadroparin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

148 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (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

Actual Study Start Date :

Sep 1, 2013

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dabigatran Dabigatran	Drug: Dabigatran Dabigatran
Active Comparator: Rivaroxaban Rivaroxaban	Drug: Rivaroxaban Rivaroxaban
Active Comparator: Nadroparin Nadroparin	Drug: Nadroparin Nadroparin

Arm

Intervention/Treatment

Active Comparator: Dabigatran

Dabigatran

Drug: Dabigatran

Dabigatran

Active Comparator: Rivaroxaban

Rivaroxaban

Drug: Rivaroxaban

Rivaroxaban

Active Comparator: Nadroparin

Nadroparin

Drug: Nadroparin

Nadroparin

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 110 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.