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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2011 by Martini Hospital Groningen
Sponsor:
Information provided by (Responsible Party):
Marinus van Hulst, Martini Hospital Groningen
ClinicalTrials.gov Identifier:
NCT01431456
First received: September 7, 2011
Last updated: September 8, 2011
Last verified: September 2011
  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

Resource links provided by NLM:


Further study details as provided by Martini Hospital Groningen:

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 [ 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01431456

Contacts
Contact: Marinus van Hulst, PharmD PhD +31 50 5247381 hulstr@mzh.nl

Locations
Netherlands
Martini Ziekenhuis Not yet recruiting
Groningen, Netherlands
Principal Investigator: Marinus van Hulst, PharmD PhD         
Sponsors and Collaborators
Martini Hospital Groningen
  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 July 22, 2014