MINS (myocardial injury after noncardiac surgery) MedDRA version: 20.1 Level: PT Classification code 10066592 Term: Post procedural myocardial infarction System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Interventions
Trade Name: Pradaxa
Product Name: Dabigatran
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DABIGATRAN ETEXILATE
CAS Number: 21
Sponsors
Hamilton Health Sciences Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible if they: 1. have undergone noncardiac surgery; 2. are =45 years of age; 3. 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 4. provide written informed consent to participate while still in hospital after their index surgery and within 35 days of suffering their MINS. 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 560 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1190
Exclusion criteria
Exclusion criteria: We will exclude patients meeting any of the following criteria: 1. hypersensitivity or known allergy to dabigatran; 2. history of intracranial, intraocular, or spinal bleeding; 3. hemorrhagic disorder or bleeding diathesis; 4. known hepatic impairment or liver disease expected to have an impact on survival; 5. condition that requires therapeutic dose anticoagulation (e.g., prosthetic heart valve, venous thromboembolism, atrial fibrillation); 6. currently using or plan to initiate rifampicin, cyclosporine, itraconazole, tacrolimus, ketoconazole, or dronedarone; 7. women who are pregnant, breastfeeding, or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study; 8. investigator considers the patient unreliable regarding requirement for study follow-up or study drug compliance; OR 9. previously enrolled in the MANAGE Trial. We will also exclude patients in whom any of the following criteria persist beyond 35 days of their suffering MINS: 1. the attending surgeon believes it is not safe to initiate therapeutic dose anticoagulation therapy; 2. 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; 3. 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 4. estimated glomerular filtration rate (eGFR) <35 ml/min as estimated by calculated creatinine clearance. 5. 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 We will exclude patients meeting any of the following criteria: 1. hypersensitivity or known allergy to omeprazole; 2. requirement for a proton pump inhibitor, an H2-receptor antagonist, sucralfate, atazanavir, clopidogrel, or misoprostol; 3. esophageal or gastric variceal disease; OR 4. patient declines participation in the omeprazole arm of MANAGE.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of dabigatran versus placebo on the risk of a major vascular complication (i.e., a composite of vascular mortality, nonfatal myocardial infarction, nonfatal non-hemorrhagic stroke, nonfatal peripheral arterial thrombosis, nonfatal amputation, and nonfatal symptomatic venous thromboembolism [i.e., symptomatic pulmonary embolism or symptomatic proximal deep venous thrombosis]) and, to determine the effect of omeprazole versus placebo on the risk of a major upper gastrointestinal complication (i.e., a composite of overt gastroduodenal bleeding, overt upper gastrointestinal bleeding of unknown origin, or upper gastrointestinal perforation). ; Secondary Objective: 1) effect of dabigatran on all-cause mortality, vascular mortality, MI, non-hemorrhagic stroke, cardiac revascularization procedure, symptomatic venous thromboembolism, amputation, peripheral arterial thrombosis, and rehospitalization for vascular reasons. 2) effect of omeprazole on the risk of upper GI complication (i.e., composite of overt gastroduodenal bleeding, overt upper GI bleeding of unknown origin, symptomatic gastroduodenal ulcer, GI pain with underlying multiple gastroduodenal erosions, or upper GI perforation). 3) effect of omeprazole on the risk of a major vascular complication (as defined in primary objective). 4) effect of omeprazole on overt gastroduodenal bleeding, overt esophageal bleeding, overt upper GI bleeding of unknown origin, symptomatic gastroduodenal ulcer, GI pain with underlying multiple gastroduodenal erosions, upper GI perforation, and bleeding of assumed occult GI origin with a documented drop in hemoglobin of =3.0 g/dL, dyspepsia, and mortality. ; Primary end point(s): The primary outcome for da | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcomes for dabigatran include each of the following individual secondary outcomes: o vascular mortality o all-cause mortality, o myocardial infarction, o non-hemorrhagic stroke, o cardiac revascularization procedure, o symptomatic venous thromboembolism (i.e., symptomatic pulmonary embolism or symptomatic deep venous thrombosis), o amputation, o peripheral arterial thrombosis, and o rehospitalization for vascular reasons. The safety outcomes for dabigatran include: o a composite of life-threatening bleeding, major bleeding, and critical organ bleeding (primary safety outcome), o life-threatening bleeding, o major bleeding, o critical organ bleeding, o intracranial bleeding, o hemorrhagic stroke o significant lower gastrointestinal bleeding, o non-significant lower gastrointestinal bleeding, o minor bleeding, o fracture, and o dyspepsia. Secondary outcomes for omeprazole include: o upper gastrointestinal complication (i.e., composite of overt gastroduodenal bleeding, overt upper gastrointestinal bleeding of unknown origin, symptomatic gastroduodenal ulcer, gastrointestinal pain with underlying multiple gastroduodenal erosions, or upper gastrointestinal perforation), o a major vascular complication (i.e., a composite of vascular mortality, nonfatal myocardial infarction, nonfatal non-hemorrhagic stroke, nonfatal peripheral arterial thrombosis, nonfatal amputation, and nonfatal symptomatic venous thromboembolism), o overt gastroduodenal bleeding, o overt esophageal bleeding o overt upper gastrointestinal ble | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, Colombia, Czech Republic, Denmark, Germany, India, Italy, Kenya, Peru, Philippines, Portugal, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactMANAGE Project Office
Population Health Research Institute, Hamilton Health Sciences Corporation
Outcome results
None listed