- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01184989
Treatment of Patients Undergoing Primary Unilateral Elective Total Knee or Hip Replacement With Dabigatran Etexilate
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Graz, Austria
- 1160.86.43001 Boehringer Ingelheim Investigational Site
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Wien, Austria
- 1160.86.43003 Boehringer Ingelheim Investigational Site
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Alberta
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Red Deer, Alberta, Canada
- 1160.86.01001 Boehringer Ingelheim Investigational Site
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Nova Scotia
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Halifax, Nova Scotia, Canada
- 1160.86.01002 Boehringer Ingelheim Investigational Site
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Prince Edward Island
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Charlottetown, Prince Edward Island, Canada
- 1160.86.01003 Boehringer Ingelheim Investigational Site
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Prague 5, Czechia
- 1160.86.42002 Boehringer Ingelheim Investigational Site
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Jyväskylä, Finland
- 1160.86.35801 Boehringer Ingelheim Investigational Site
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Hilversum, Netherlands
- 1160.86.31002 Boehringer Ingelheim Investigational Site
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Hässleholm, Sweden
- 1160.86.46002 Boehringer Ingelheim Investigational Site
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Mölndal, Sweden
- 1160.86.46001 Boehringer Ingelheim Investigational Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Patients scheduled for primary unilateral elective total knee or hip replacement, male or female being 18 years or older
- Moderate renal impairment (CrCl 30-50 mL/min)
- Written informed consent
- Caucasian patients
Exclusion criteria:
- Patients weighing less than 40 kg.
- Patients requiring chronic treatment with anticoagulants (e.g. vitamin K antagonists; e.g. patients with atrial fibrillation, patients with artificial heart valves, etc.).
Patients who in the investigator's judgment were 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 randomization
Any history of hemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm
Any arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities
Presence of malignant neoplasms at higher risk of bleeding
Known or suspected oesophageal varices
Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days
Treatment with anticoagulants, clopidogrel, ticlopidine, abciximab, aspirin >162.5 mg/day or non-steroidal anti-inflammatory drug (NSAID) with t1/2>12 hours within 7 days prior to hip or knee replacement surgery OR anticipated need while the patient was 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
- Recent unstable cardiovascular disease (in the investigator's opinion) such as uncontrolled hypertension, that was ongoing at the time of enrolment or history of myocardial infarction within 3 months of enrolment.
- Ongoing treatment for VTE.
- Liver disease expected to have any potential impact on survival (i.e. hepatitis B or C, cirrhosis) or ALT/AST >3x upper limit of normal range (ULN). This did not include Gilbert's syndrome or hepatitis A with complete recovery.
- Known severe renal insufficiency (CrCl <30 mL/min) and patients with mild renal insufficiency (CrCl >50 mL/min) or normal renal function.
- Planned anaesthesia with post-operative indwelling epidural catheters.
Pre-menopausal women (last menstruation <=1 year prior to signing informed consent), who were:
Pregnant
Nursing
Of child-bearing potential and were NOT practicing acceptable methods of birth control, or did NOT plan to continue practicing an acceptable method throughout the study. Acceptable methods of birth control included intrauterine device; oral, implantable or injectable contraceptives and surgical sterility
- Hypersensitivity to dabigatran etexilate or to any of excipients.
- Participation in a clinical trial within 30 days of enrolment.
- 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.
- Previous participation in this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: Dabigatran etexilate
open label, once daily dose approved by EMEA and Health Canada
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once daily approved dose by EMEA and Health Canada
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Dabigatran Concentration in Plasma, Estimated From Local Hemoclot®
Time Frame: Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di
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The Hemoclot® test kit measures the dTT (diluted Thrombin time). In the present trial, as a first step, the dTT in calibration samples that had known Dabigatran concentrations was measured locally with the Hemoclot® test kit, and a linear calibration curve was fitted to the data from the calibration samples. Thereafter, for each patient at each time-point, the dTT was measured with the Hemoclot® kit and the Dabigatran concentration was read off from the calibration curve. These estimated concentrations are compared with concentrations measured in parallel with HPLC-MS/MS. As the trial objective is the method comparison and not the detection of the absolute concentrations of either of the methods, the result is reported as a relative bioavailability [%], see "Statistical Analysis 1" below. Only concentrations >= LLOQ (Lower Limit of concentration) are included in the quantitative comparison. |
Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di
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Dabigatran Concentration in Plasma, Estimated From Central Hemoclot®
Time Frame: Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di
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The Hemoclot® test kit measures the dTT (diluted Thrombin time). In the present trial, as a first step, the dTT in calibration samples that had known Dabigatran concentrations was measured centrally with the Hemoclot® test kit, and a linear calibration curve was fitted to the data from the calibration samples. Thereafter, for each patient at each time-point, the dTT was measured with the Hemoclot® kit and the Dabigatran concentration was read off from the calibration curve. These estimated concentrations are compared with concentrations measured in parallel with HPLC-MS/MS. As the trial objective is the method comparison and not the detection of the absolute concentrations of either of the methods, the result is reported as a relative bioavailability [%], see "Statistical Analysis 1" below. Only concentrations >= LLOQ (Lower Limit of concentration) are included in the quantitative comparison. |
Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di
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Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS
Time Frame: At day 6 before drug intake (di), at 1h, 2h, 4h, 8h and 24h after di
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Dabigatran Concentration in Plasma, measured with HPLC-MS/MS - Most relevant timepoints are reported here, ie timepoints of day 6
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At day 6 before drug intake (di), at 1h, 2h, 4h, 8h and 24h after di
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Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Kidney Diseases
- Urologic Diseases
- Embolism and Thrombosis
- Renal Insufficiency
- Thromboembolism
- Venous Thromboembolism
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Dabigatran
Other Study ID Numbers
- 1160.86
- 2010-018723-26 (EudraCT Number: EudraCT)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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