Treatment of Patients Undergoing Primary Unilateral Elective Total Knee or Hip Replacement With Dabigatran Etexilate
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ClinicalTrials.gov Identifier: NCT01184989 |
Recruitment Status :
Completed
First Posted : August 19, 2010
Results First Posted : May 23, 2014
Last Update Posted : September 25, 2018
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Arthroplasty, Replacement Prevention of Venous Thromboembolism Moderate Renal Impairment (CrCl 30-50 mL/Min) | Drug: Dabigatran etexilate | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 142 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Prevention |
Official Title: | 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 Start Date : | August 2010 |
Actual Primary Completion Date : | April 2013 |
Actual Study Completion Date : | April 2013 |

Arm | Intervention/treatment |
---|---|
Dabigatran etexilate
open label, once daily dose approved by EMEA and Health Canada
|
Drug: Dabigatran etexilate
once daily approved dose by EMEA and Health Canada |
- 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 ]
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.
- 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 ]
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.
- 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 ]Dabigatran Concentration in Plasma, measured with HPLC-MS/MS - Most relevant timepoints are reported here, ie timepoints of day 6

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01184989
Austria | |
1160.86.43001 Boehringer Ingelheim Investigational Site | |
Graz, Austria | |
1160.86.43003 Boehringer Ingelheim Investigational Site | |
Wien, Austria | |
Canada, Alberta | |
1160.86.01001 Boehringer Ingelheim Investigational Site | |
Red Deer, Alberta, Canada | |
Canada, Nova Scotia | |
1160.86.01002 Boehringer Ingelheim Investigational Site | |
Halifax, Nova Scotia, Canada | |
Canada, Prince Edward Island | |
1160.86.01003 Boehringer Ingelheim Investigational Site | |
Charlottetown, Prince Edward Island, Canada | |
Czechia | |
1160.86.42002 Boehringer Ingelheim Investigational Site | |
Prague 5, Czechia | |
Finland | |
1160.86.35801 Boehringer Ingelheim Investigational Site | |
Jyväskylä, Finland | |
Netherlands | |
1160.86.31002 Boehringer Ingelheim Investigational Site | |
Hilversum, Netherlands | |
Sweden | |
1160.86.46002 Boehringer Ingelheim Investigational Site | |
Hässleholm, Sweden | |
1160.86.46001 Boehringer Ingelheim Investigational Site | |
Mölndal, Sweden |
Study Chair: | Boehringer Ingelheim | Boehringer Ingelheim |
Responsible Party: | Boehringer Ingelheim |
ClinicalTrials.gov Identifier: | NCT01184989 |
Other Study ID Numbers: |
1160.86 2010-018723-26 ( EudraCT Number: EudraCT ) |
First Posted: | August 19, 2010 Key Record Dates |
Results First Posted: | May 23, 2014 |
Last Update Posted: | September 25, 2018 |
Last Verified: | August 2018 |
Renal Insufficiency Thromboembolism Venous Thromboembolism Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Kidney Diseases Urologic Diseases |
Dabigatran Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anticoagulants |