A Randomized Pilot Study Comparing the Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 110 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Nadroparin
Nadroparin
干预措施: Nadroparin (Drug)
Dabigatran
Dabigatran
干预措施: Dabigatran (Drug)
Rivaroxaban
Rivaroxaban
干预措施: Rivaroxaban (Drug)
结局指标
主要结局
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
时间窗: 135 days
Major and clinically relevant non-major bleeding
次要结局
未报告次要终点
研究者
Marinus van Hulst
Hospital Pharmacist
Martini Hospital Groningen