E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary VTE prevention in patients with moderate renal impairment (Creatinine Clearance 30-50 ml/min) following total hip or knee replacement surgery |
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E.1.1.1 | Medical condition in easily understood language |
Primary VTE prevention in patients with moderate renal impairment (Creatinine Clearance 30-50 ml/min) following total hip or knee replacement surgery |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Canada |
Czech Republic |
Finland |
Netherlands |
Sweden |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |