RandomisEd Dabigatran Etexilate dose finding study in patients with acute coronary syndromes post index Event with additional risk factors for cardiovascular complications also receiving aspirin and clopidogrel: Multi-centre, prospective, placebo controlled, group dose escalation trial (RE-DEEM STUDY) - RE-DEEM

Conditions: Acute coronary syndromes
MedDRA version: 9.1Level: PTClassification code 10051592Term: Acute coronary syndrome

Registration Number: EUCTR2007-004301-99-GB

Lead Sponsor: Boehringer Ingelheim Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 2220

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 65 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. Ticlopidine or prasugrel can be used instead of clopidogrel, for a duration at the investigator’s discretion, provided that this antiplatelet agent is licensed for use in that country and is being taken at time of randomisation.

5. The patient or the patient’s legally acceptable representative must be able to give
informed consent in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and local legislation.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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) unless the malignancy was a form of skin cancer (excluding malignant melanoma) which was completely eradicated.
4. Anaemia (haemoglobin < 10g/dL) or thrombocytopenia (platelet count < 100 x 10 to the power of 9/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, quinidine or any cytotoxic/myelosuppressive or immunologic drug or radiation therapy.
16. Patients not willing or able to comply w

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.<br><br>;Secondary Objective: 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.<br><br>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.<br>;Primary end point(s): The composite of major and clinically relevant minor bleeding events during six months of treatment.

Secondary Outcome Measures