E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037377 |
E.1.2 | Term | Pulmonary embolism |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047251 |
E.1.2 | Term | Venous thrombosis deep (limbs) |
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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 |
The primary objective is to investigate the efficacy of dabigatran etexilate 150 mg bid administered orally compared to warfarin PRN to maintain an INR of 2.0-3.0 for 6 month treatment period according to the study endpoints in patients with acute symptomatic Venous Thromboembolic Event (VTE is defined as the composite incidence of Deep Vein Thrombosis of the leg and Pulmonary Embolism). |
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E.2.2 | Secondary objectives of the trial |
The investigation of other selected efficacy aspects and safety are regarded as secondary objective of this trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Acute symptomatic uni- or bilateral DVT of the leg involving proximal veins, and/or PE confirmed by definitive objective clinical test in patients for whom at least 6 months of anticoagulant therapy is considered appropriate by the investigator(proximal veins are: trifurcation area, popliteal, superficial femoral, deep femoral, common femoral and iliac vein). 2.Male or female, being 18 years of age or older 3.Written informed consent for study participation |
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E.4 | Principal exclusion criteria |
1. Overt symptoms of VTE for longer than 2 weeks prior to enrolment 2. PE satisfying at least one of the following criteria: Haemodynamic instability Embolectomy is indicated or performed Thrombolytic therapy is indicated or performed Suspected source of PE is other than the legs 3. Actual or anticipated use of vena cava filter 4. Contraindications to anticoagulant therapy including contraindications to heparins or other alternate approved therapy used for initial treatment, and warfarin 5. Patients who in the investigators opinion should not be treated with warfarin 6. Allergy to heparins (including history of heparin induced thrombocytopenia) or other alternate approved therapy used for initial treatment, warfarin or dabigatran, or to one of the excipients included in these medications 7. In case of anticipated study related diagnostic procedures requiring contrast medium (e.g. contrast venography or pulmonary angiography): Elevated serum creatinine, which in the investigators opinion contraindicates these examinations Known allergy to radio opaque contrast media or iodine, which in the investigators opinion contraindicates these examinations 8. Patients who in the investigators judgement are perceived as having an excessive risk of bleeding, for example because of: Hemorrhagic disorder or bleeding diathesis Trauma or major surgery within the last month or as long as an excessive risk of bleeding persists after these events, or planned major surgery Any of the following intracranial pathologies: neoplasm, arteriovenous malformation or aneurysm History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra articular bleeding Gastrointestinal haemorrhage within the past 3 months Symptomatic or endoscopically documented gastro duodenal ulcer disease in the previous 30 days Treatment with thrombolytic agents within 14 days before enrolment Anticipated need of quinidine or other restricted medication during the treatment period Known thrombocytopenia (platelet count < 100·10**9/L) 9. Known anaemia (haemoglobin < 100 g/L) 10. Need of anticoagulant treatment for disorders other than VTE 11. Recent unstable cardiovascular disease, such as uncontrolled hypertension at the time of enrolment (investigators judgement), acute bacterial endocarditis or history of myocardial infarction within the last 3 months 12. Elevated Aspartate-aminotransferase (AST) or Alanine-aminotransferase (ALT) > 3x ULN based on the local lab results obtained at screening and prior to randomisation (or central screening lab if available on time) 13. Known liver disease expected to have any potential impact on survival (e.g. acute hepatitis, possibly active hepatitis B, hepatitis C or cirrhosis, but not Gilberts syndrome or hepatitis A with complete recovery) 14. Severe renal impairment (estimated creatinine clearance <= 30 ml/min) 15. Women who are pregnant, nursing, or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study (NOTE: A negative pregnancy test must be obtained for any woman of childbearing potential prior to entry into the study) 16. Patients considered unsuitable for inclusion by the investigator, e.g. because considered unreliable to comply with the requirements for follow-up during the study and/or compliance with study drug administration, has a life expectancy less than the expected duration of the trial due to concomitant disease, or has any condition which in the opinion of the investigator would not allow safe participation in the study (e.g., drug addiction, alcohol abuse) 17. Participation in another clinical trial with an investigational drug during the last 30 days or previous participation in this study or RE-COVER I (1160.53) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Composite of recurrent symptomatic venous thromboembolism and deaths related to VTE within 6 months (VTE is defined as the composite incidence of DVT and PE). |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 74 |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |