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 | PT |
E.1.2 | Classification code | 10051592 |
E.1.2 | Term | Acute coronary syndrome |
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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 purpose of this trial is to evaluate the safety and indicators of efficacy of up to 4 doses of orally administered dabigatran etexilate, administered twice daily compared to placebo when given in addition to dual antiplatelet treatment in patients with an index event at high risk for new ischaemic cardiovascular events.
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E.2.2 | Secondary objectives of the trial |
Exploratory evaluation of total dabigatran trough plasma concentration versus the bleeding risk on the background of concomitant ASA and clopidogrel and the relationship of trough plasma levels to biomarkers.
The effects of dabigatran etexilate treatment on markers of myocardial dysfunction and damage, renal dysfunction, inflammation, platelet activation and other markers of coagulation activity, will be explored.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub studies are part of the main study and will be detailed as appendices of the main study, they do not have separate titles
Details will follow by protocol amendment.
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E.3 | Principal inclusion criteria |
1. Male and female adults 2. Acute coronary syndrome (ACS) index event of myocardial infarction (MI)
MI must be documented by: Detection of elevated values of cardiac biomarkers above the 99th percentile of the upper reference limittogether with evidence of myocardial ischaemia with at least one of the following: • Ischaemic symptoms • ECG changes indicative of new ischaemia • Development of pathological Q waves in the ECG
3. At least one of the following criteria of higher risk • Age 70 years or above • Type I or II diabetes on treatment • Previous MI • Peripheral arterial disease, as evidenced by either previous intervention or an ankle-brachial index < 0.9 • left bundle branch block • congestive heart failure requiring treatment • Moderate renal insufficiency creatinine clearance 30 - 60mL/min • No revascularisation for the index event
4. Ongoing treatment with dual antiplatelet therapy (ASA and clopidogrel) at the time of randomisation.
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E.4 | Principal exclusion criteria |
1. Ongoing or planned treatment with long-term oral anticoagulants for alternative indications during the course of the study (e.g. AF, prosthetic heart valves, haemodynamically relevant valve disease that is expected to require surgical intervention) 2. Severe, disabling stroke within the previous 6 months, or any stroke within the previous 14 days 3. Conditions associated with an increased risk of bleeding: • Major surgery (including CABG) in the previous month or scheduled for surgery during the course of the study • History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra articular bleeding unless the causative factor has been permanently eliminated or repaired (e.g.by surgery) • Gastrointestinal haemorrhage that resulted in hospitalisation or treatment within the past year • Endoscopically documented gastroduodenal ulcer disease in the previous 30 days • Haemorrhagic disorder or bleeding diathesis • Fibrinolytic agents within 48 hours of study entry • Uncontrolled hypertension (systolic blood pressure (SBP) > 180mmHg and/or diastolic blood pressure (DBP) > 100mmHg) • Recent malignancy or radiation therapy (≤ 6 months) 4. Anaemia (haemoglobin < 10g/dL) or thrombocytopenia (platelet count < 100 109/L) at screening (Visit 1) 5. Index event is a peri-procedural Myocardial infarction at percutaneous coronary intervention or coronary artery bypass graft 6. If a coronary angiogram for the index event shows normal coronary arteries 7. Active infective endocarditis, pericarditis or pericardial effusion 8. Severe congestive heart failure New York Heart Association (NYHA) Class IV 9. Severe renal impairment (estimated CrCl calculated by Cockcroft-Gault equation ≤ 30mL/min) 10. Liver disease as indicated by one of the following: • Prior and persistent ALT > 3 X ULN, or alkaline phosphatase (Alk Phos) > 2 X ULN Note: ALT elevation because of MI is not an exclusion criterion • Known active hepatitis C (as evidenced by positive hepatitis C virus ribonucleic acid assay by sensitive polymerase chain reaction (PCR) based assay, such as Roche Monitor or Bayer assay) • Active hepatitis B (HBs antigen + or anti HBc IgM+) • Active hepatitis A 11. Pre-menopausal (last menstruation ≤ 1 year prior to screening) sexually active women who: • are pregnant or nursing • are not surgically sterile • are of child bearing potential and not practicing an acceptable method of birth control, or does not plan to continue practising an acceptable method of birth control throughout the trial (acceptable methods include intrauterine devices (IUD), oral, implantable or injectable contraceptives, double barrier or vasectomised partner) 12. A pregnancy test indicating pregnancy in a woman of childbearing potential at screening (Visit 1) 13. Patients who have participated in another trial with an investigational drug or device within the last 4 weeks or 5 half-lives (whichever is greater) preceding the screening visit 14. Patients with a known allergy to dabigatran etexilate or to the excipients used for the capsule of the drug. 15. Patients also requiring chronic oral non steroidal anti inflammatory drugs (NSAIDs), chronic systemic use of corticosteroids, or any cytotoxic/myelosuppressive or immunologic drug or radiation therapy. 16. Patients not willing or able to comply with the protocol requirements for the duration of the study 17. Patients considered unreliable by the investigator concerning 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)
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E.5 End points |
E.5.1 | Primary end point(s) |
The composite of major and clinically relevant minor bleeding events during six months of treatment. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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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End of trial is the last subject last visit |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |