An open label, non-comparative, pharmacokinetic and pharmacodynamic study to evaluate the effect of Dabigatran Etexilate on coagulation parameters including a calibrated thrombin time test in patients with moderate renal impairment (creatinine clearance 30-50 ml/min) undergoing primary unilateral elective total knee or hip replacement surgery

Conditions: Primary VTE prevention in patients with moderate renal impairment (Creatinine Clearance 30-50 ml/min) following total hip or knee replacement surgery
MedDRA version: 13.1Level: LLTClassification code 10049909Term: Venous thromboembolism prophylaxisSystem Organ Class: 10042613 - Surgical and medical procedures

Registration Number: EUCTR2010-018723-26-CZ

Lead Sponsor: Boehringer Ingelheim RCV GmbH & Co KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 120

Inclusion Criteria

1.Patients scheduled for primary unilateral elective total knee or hip replacement, male or female being 18 years or older
2.Moderate renal impairment (creatinine clearance 30-50 ml/min)
3.Written informed consent
4.Caucasian patients

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patients weighing less than 40 kg.
2.Patients requiring chronic treatment with anticoagulants (e.g. vitamin K antagonists; e.g. patients with atrial fibrillation, patients with artificial heart valves, etc.).
3.Patients who in the investigator’s judgement are perceived as having an excessive risk of bleeding, for example:
•constitutional or acquired coagulation disorders
•history of bleeding diathesis
•Clinically relevant bleeding (gastrointestinal, pulmonary, intraocular or urogenital bleeding) within 3 months of enrolment
•Major surgery or trauma (e.g., hip fracture) within 3 months of enrolment
•History of thrombocytopenia, including heparin-induced thrombocytopenia, or a platelet count <100,000 cells/microliter at randomisation
•Any history of haemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, AV malformation or aneurysm
•Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days
•Treatment with anticoagulants, clopidogrel, ticlopidine, abciximab, aspirin >162.5 mg/day or NSAID with t 1/2 >12 hours within 7 days prior to hip or knee replacement surgery OR anticipated need while the patient is receiving study medication and prior to 24 hours after the last administration of study medication (COX-2 selective inhibitors are allowed) because of anticipated need of quinidine, verapamil or other restricted medication during the treatment period
4.Recent unstable cardiovascular disease (in the investigator’s opinion) such as uncontrolled hypertension, that is ongoing at the time of enrolment or history of myocardial infarction within 3 months of enrolment.
5.Ongoing treatment for VTE.
6.Liver disease expected to have any potential impact on survival (ie, hepatitis B or C, cirrhosis) or ALT/AST >3 x ULN. This does not include Gilbert’s syndrome or hepatitis A with complete recovery.
7.Known severe renal insufficiency (CrCl <30 ml/min) and patients with mild renal insufficiency (CrCl >50 ml/min) or normal renal function.
8.Planned anaesthesia with post-operative indwelling epidural catheters.
9.Pre-menopausal women (last menstruation =1 year prior to signing informed consent), who:
•Are pregnant.
•Are nursing.
•Are of child-bearing potential and are NOT practicing acceptable methods of birth control, or do NOT plan to continue practicing an acceptable method throughout the study. Acceptable methods of birth control include intrauterine device; oral, implantable or injectable contraceptives and surgical sterility.
10.Hypersensitivity to dabigatran etexilate or to any of excipients.
11.Participation in a clinical trial within 30 days of enrolment.
12.Known alcohol or drug abuse which would interfere with completion of the study; patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration.
13.Previous participation in this study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the comparability of the estimated dabigatran concentration in plasma via calibrated Hemoclot® and the measured dabigatran concentrations assessed in a central lab in patients with moderate renal impairment (creatinine clearance 30-50 ml/min) undergoing primary unilateral elective total knee or hip replacement surgery.<br><br>To evaluate the correlation between total Dabigatran plasma concentration and coagulation parameters using the Hemoclot® Direct Thrombin Inhibitor Assay, aPTT and ECT in patients with moderate renal impairment (creatinine clearance 30-50 ml/min) undergoing primary unilateral elective total knee or hip replacement surgery in steady state condition.<br>;Secondary Objective: ;Primary end point(s):

Secondary Outcome Measures