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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01661101
Registration number
NCT01661101
Ethics application status
Date submitted
7/08/2012
Date registered
9/08/2012
Date last updated
26/03/2018
Titles & IDs
Public title
Management of Myocardial Injury After Noncardiac Surgery Trial
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Scientific title
A 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
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Secondary ID [1]
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2011-006056-37
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Secondary ID [2]
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1160.143
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Universal Trial Number (UTN)
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Trial acronym
MANAGE
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Myocardial Injury After Noncardiac Surgery (MINS)
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Condition category
Condition code
Skin
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Other skin conditions
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Dabigatran
Treatment: Drugs - Placebo (for Dabigatran)
Treatment: Drugs - Omeprazole
Treatment: Drugs - Placebo (for Omeprazole)
Experimental: Dabigatran - Dabigatran 110 mg capsule taken twice daily
Experimental: Omeprazole - Omeprazole 20 mg capsule taken once daily
Placebo comparator: Placebo (dabigatran) - Dabigatran placebo taken twice daily
Placebo comparator: Placebo (omeprazole) - Omeprazole placebo taken once daily
Treatment: Drugs: Dabigatran
Dabigatran 110 mg taken twice daily
Treatment: Drugs: Placebo (for Dabigatran)
Dabigatran placebo taken twice daily
Treatment: Drugs: Omeprazole
Omeprazole 20 mg capsule taken once daily
Treatment: Drugs: Placebo (for Omeprazole)
Omeprazole placebo taken once daily
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Major vascular complication (for Dabigatran)
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Assessment method [1]
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A composite of the number of patients suffering 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).
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Timepoint [1]
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Average of 1 year follow-up
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Primary outcome [2]
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Major upper gastrointestinal complication (for Omeprazole)
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Assessment method [2]
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A composite of the number of patients suffering overt gastroduodenal bleeding, overt upper gastrointestinal bleeding of unknown origin, or upper gastrointestinal perforation.
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Timepoint [2]
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Average of 1 year follow-up
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Secondary outcome [1]
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Individual secondary outcomes for Dabigatran
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Assessment method [1]
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The number of patients suffering all-cause mortality, vascular mortality, myocardial infarction, non-hemorrhagic stroke, cardiac revascularization procedure, symptomatic venous thromboembolism (i.e., symptomatic pulmonary embolism or symptomatic proximal deep venous thrombosis), amputation, peripheral arterial thrombosis, and rehospitalization for vascular reasons.
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Timepoint [1]
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Average of 1 year follow-up
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Secondary outcome [2]
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Upper gastrointestinal complication for Omeprazole
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Assessment method [2]
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A composite of the number of patients suffering overt gastroduodenal bleeding, overt upper gastrointestinal bleeding of unknown origin, symptomatic gastroduodenal ulcer, gastrointestinal pain with underlying multiple gastroduodenal erosions, or upper gastrointestinal perforation.
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Timepoint [2]
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Average of 1 year follow-up
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Secondary outcome [3]
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Major vascular complication for Omeprazole
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Assessment method [3]
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A composite of the number of patients suffering 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).
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Timepoint [3]
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Average of 1 year follow-up
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Secondary outcome [4]
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Individual secondary outcomes for Omeprazole
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Assessment method [4]
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The number of patients suffering overt gastroduodenal bleeding, overt esophageal bleeding, overt upper gastrointestinal bleeding of unknown origin, symptomatic gastroduodenal ulcer, gastrointestinal pain with underlying multiple gastroduodenal erosions, upper gastrointestinal perforation, bleeding of assumed occult gastrointestinal origin with a documented drop in hemoglobin of = 3.0 g/dL, dyspepsia, and mortality.
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Timepoint [4]
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Average of 1 year follow-up
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Secondary outcome [5]
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Safety outcomes for Dabigatran
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Assessment method [5]
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1. A composite of the number of patients suffering life-threatening bleeding, major bleeding, and critical organ bleeding (i.e., intracranial, intraocular, intraspinal, pericardial, retroperitoneal).
2. The number of patients suffering life-threatening bleeding, major bleeding, critical organ bleeding, intracranial bleeding, minor bleeding, hemorrhagic stroke, significant lower gastrointestinal bleeding, non-significant lower gastrointestinal bleeding, fracture, and dyspepsia.
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Timepoint [5]
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Average of 1 year follow-up
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Secondary outcome [6]
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Safety outcomes for Omeprazole
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Assessment method [6]
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The number of patients suffering Clostridium difficile-associated diarrhea, diarrhea, community-acquired pneumonia, and fractures.
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Timepoint [6]
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Average of 1 year follow-up
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Eligibility
Key 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 within 35 days of suffering their MINS.
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Minimum age
45
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Patients meeting any of the following criteria will be excluded:
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.
Also excluded will be 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:
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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Factorial
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Other design features
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Phase
Phase 3
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/01/2013
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Date of last participant enrolment
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Actual
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Date of last data collection
Anticipated
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Actual
1/03/2018
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Sample size
Target
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Accrual to date
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Final
1754
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Westmead Hospital - Westmead
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Recruitment postcode(s) [1]
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2145 - Westmead
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Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Other
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Name
Population Health Research Institute
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Ethics approval
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Summary
Brief summary
Patients who have myocardial injury after noncardiac surgery are at a higher risk of dying than those who do not. One in 10 patients with myocardial injury will die within 30 days of surgery. This risk of death exists up to one year after myocardial injury. There are currently no treatments or guidelines available for heart injury after surgery, but there is evidence that taking a blood-thinner can prevent some of the deaths, both in the short and long-term. The purpose of this trial is to test the effect of two drugs (dabigatran and omeprazole) that may prevent mortality, major cardiovascular complications and major upper gastrointestinal bleeding in patients who have had myocardial injury after noncardiac surgery.
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Trial website
https://clinicaltrials.gov/study/NCT01661101
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Trial related presentations / publications
Duceppe E, Yusuf S, Tandon V, Rodseth R, Biccard BM, Xavier D, Szczeklik W, Meyhoff CS, Franzosi MG, Vincent J, Srinathan SK, Parlow J, Magloire P, Neary J, Rao M, Chaudhry NK, Mayosi B, de Nadal M, Popova E, Villar JC, Botto F, Berwanger O, Guyatt G, Eikelboom JW, Sessler DI, Kearon C, Pettit S, Connolly SJ, Sharma M, Bangdiwala SI, Devereaux PJ. Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE). Can J Cardiol. 2018 Mar;34(3):295-302. doi: 10.1016/j.cjca.2018.01.020. Epub 2018 Feb 2. Lamy A, Tong W, Mian R, Vincent J, Szczeklik W, Biccard BM, Duceppe E, Franzosi MG, Srinathan SK, Meyhoff CS, Parlow J, Xavier D, Devereaux PJ. The Cost Implications of Dabigatran in Patients with Myocardial Injury After Non-Cardiac Surgery. Am J Cardiovasc Drugs. 2022 Jan;22(1):83-91. doi: 10.1007/s40256-021-00489-3. Epub 2021 Jul 26. Devereaux PJ, Duceppe E, Guyatt G, Tandon V, Rodseth R, Biccard BM, Xavier D, Szczeklik W, Meyhoff CS, Vincent J, Franzosi MG, Srinathan SK, Erb J, Magloire P, Neary J, Rao M, Rahate PV, Chaudhry NK, Mayosi B, de Nadal M, Iglesias PP, Berwanger O, Villar JC, Botto F, Eikelboom JW, Sessler DI, Kearon C, Pettit S, Sharma M, Connolly SJ, Bangdiwala SI, Rao-Melacini P, Hoeft A, Yusuf S; MANAGE Investigators. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet. 2018 Jun 9;391(10137):2325-2334. doi: 10.1016/S0140-6736(18)30832-8. Erratum In: Lancet. 2018 Jul 7;392(10141):30. doi: 10.1016/S0140-6736(18)31481-8.
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Public notes
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Contacts
Principal investigator
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P.J. Devereaux, MD, PhD
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Population Health Research Institute
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT01661101
Download to PDF