MANAGEA Large, International, Randomized, Placebo-controlled Trial to Assess the Impact of Dabigatran (a Direct Thrombin Inhibitor) and Omeprazole (a Proton-pump Inhibitor) in Patients Suffering Myocardial Injury After Noncardiac Surgery

Study start date: January 1, 2013

Inclusion Criteria: Patients are eligible if they: have undergone noncardiac surgery; are ≥45 years of age; have suffered MINS based upon fulfilling one of the following criteria: A. Elevated troponin or CK-MB measurement with one or more of the following defining features i. ischemic signs or symptoms (i.e., chest, arm, neck, or jaw discomfort; shortness of breath, pulmonary edema); ii. development of pathologic Q waves present in any two contiguous leads that are ≥30 milliseconds; iii. electrocardiogram (ECG) changes indicative of ischemia (i.e., ST segment elevation [≥2 mm in leads V1, V2, or V3 OR ≥1 mm in the other leads], ST segment depression [≥1 mm], OR symmetric inversion of T waves ≥1 mm) in at least two contiguous leads; iv. new LBBB; or v. new or presumed new cardiac wall motion abnormality on echocardiography or new or presumed new fixed defect on radionuclide imaging B. Elevated troponin measurement after surgery with no alternative explanation (e.g., pulmonary embolism, sepsis) to myocardial injury; AND provide written informed consent to participate within 35 days of suffering their MINS. Exclusion Criteria: Patients meeting any of the following criteria will be excluded: hypersensitivity or known allergy to dabigatran; history of intracranial, intraocular, or spinal bleeding; hemorrhagic disorder or bleeding diathesis; known hepatic impairment or liver disease expected to have an impact on survival; condition that requires therapeutic dose anticoagulation (e.g., prosthetic heart valve, venous thromboembolism, atrial fibrillation); currently using or plan to initiate rifampicin, cyclosporine, itraconazole, tacrolimus, ketoconazole, or dronedarone; women who are pregnant, breastfeeding, or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study; investigator considers the patient unreliable regarding requirement for study follow-up or study drug compliance; OR previously enrolled in the MANAGE Trial. Also excluded will be patients in whom any of the following criteria persist beyond 35 days of their suffering MINS: the attending surgeon believes it is not safe to initiate therapeutic dose anticoagulation therapy; the attending physician believes ASA, intermittent pneumatic compression, or elastic stockings are not sufficient for venous thromboembolism (VTE) prophylaxis and that the patient requires a prophylactic-dose anticoagulant; the patient has an indwelling epidural or spinal catheter that cannot be removed, or the first dose of dabigatran will occur within 4 hours of epidural catheter removal; OR estimated glomerular filtration rate (eGFR) <35 ml/min as estimated by calculated creatinine clearance. it is expected that the patient will undergo cardiac catheterization for MINS. Exclusion Criteria Specific to Patients in the Omeprazole Factorial Component of the Trial: Patients meeting any of the following criteria: hypersensitivity or known allergy to omeprazole; requirement for a proton pump inhibitor, an H2-receptor antagonist, sucralfate, atazanavir, clopidogrel, or misoprostol; esophageal or gastric variceal disease; OR patient declines participation in the omeprazole arm of MANAGE.