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Management of Myocardial Injury After Noncardiac Surgery Trial

Information source: Population Health Research Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Myocardial Injury After Noncardiac Surgery (MINS)

Intervention: Dabigatran (Drug); Placebo (for Dabigatran) (Drug); Omeprazole (Drug); Placebo (for Omeprazole) (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Population Health Research Institute

Official(s) and/or principal investigator(s):
P.J. Devereaux, MD, PhD, Principal Investigator, Affiliation: Population Health Research Institute

Overall contact:
Jessica Vincent, M.Sc., Phone: 905-527-4322, Ext: 40635

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.

Clinical Details

Official 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Major vascular complication (for Dabigatran)

Major upper gastrointestinal complication (for Omeprazole)

Secondary outcome:

Individual secondary outcomes for Dabigatran

Upper gastrointestinal complication for Omeprazole

Major vascular complication for Omeprazole

Individual secondary outcomes for Omeprazole

Safety outcomes for Dabigatran

Safety outcomes for Omeprazole

Detailed description: Myocardial injury is the most common major vascular complication after noncardiac surgery. Worldwide approximately 10 million adults annually suffer a perioperative myocardial injury. This figure for perioperative myocardial injury represents 15-20% of all cases of myocardial infarction in all settings. Myocardial injury after noncardiac surgery carries a poor prognosis and is an independent predictor of 30-day and 1-year mortality. Myocardial injury after noncardiac surgery (MINS) differs from non-operative myocardial infarction in two ways; it has a poorer prognosis (patients suffering MINS are 2 times more likely to die within 30 days compared to non-operative myocardial infarction in the emergency room) and paradoxically its treatment is less intensive. This difference in the intensity of treatment is likely influenced by several factors including: (1) a majority of patients suffering MINS do not experience ischemic symptoms, potentially influencing physicians' perception of the severity of the event; (2) there is debate as to the pathophysiology of MINS (although emerging evidence does suggest that coronary arterial thrombosis is an important mechanism of MINS); and (3) no randomized controlled trial (RCT) has evaluated an intervention to manage MINS, and hence physicians are uncertain about the risk-benefit ratio of potential interventions (e. g., interventions that are effective in the management of non-operative myocardial infarction). From a human and economic perspective, it is a tragedy that some patients undergoing noncardiac surgery for important reasons (e. g., to obtain a cure of their cancer or to become mobile after a new prosthetic joint) fail to obtain these benefits, because they suffer MINS that ultimately takes their life. There is an urgent need for clinical trials to identify effective therapies to improve the outcomes of patients suffering MINS. There exists promising laboratory, autopsy, imaging, operative, and non-operative data suggesting that patients suffering MINS will benefit from anticoagulant therapy. Dabigatran (a direct thrombin inhibitor) warrants evaluation in the management of MINS. The major limitation of anticoagulation therapy is bleeding, and gastrointestinal bleeding represents a substantial proportion of these complications. Gastrointestinal bleeding is important in its own right, but also because it leads to cessation of anticoagulant therapy which may lead to breakthrough myocardial infarction. Omeprazole (a proton pump inhibitor) is efficacious in preventing upper gastrointestinal bleeding in patients with coronary artery disease who are taking dual antiplatelet therapy, and may benefit patients receiving anticoagulation therapy after suffering MINS. We will undertake a large international RCT to determine the impact of dabigatran in patients who have suffered MINS. We will use a partial factorial design (for patients not taking a proton pump inhibitor) to determine the impact of omeprazole in this setting. We call this RCT the Management of myocardial injury After NoncArdiac surGEry (MANAGE) Trial.

Eligibility

Minimum age: 45 Years. Maximum age: N/A. Gender(s): Both.

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 within 35 days of suffering their MINS. 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.

Locations and Contacts

Jessica Vincent, M.Sc., Phone: 905-527-4322, Ext: 40635

Favaloro Foundation, Buenos Aires C1093AAS, Argentina; Recruiting
Ernesto Duronto, MD

Hospital San Roque, Cordoba 5000, Argentina; Recruiting
Maria Parody, MD

Medical University of Vienna, Vienna 1090, Austria; Recruiting
Edith Fleischmann, MD PhD

Herlev Hospital, Herlev 2730, Denmark; Recruiting
Christian Meyhoff, MD, Principal Investigator

Nordsjaellands Hospital, Hillerød 3400, Denmark; Recruiting
Morten Bestle, MD

Vejle Hospital, Vejle 7100, Denmark; Recruiting
Kristian Martinsen, MD, Principal Investigator

Hospitalier Pitie Salpetriere, Paris 75013, France; Recruiting
Pierre Coriat, MD

Universitätsklinikum Bonn, Bonn 53105, Germany; Recruiting
Andreas Hoeft, MD, PhD, Principal Investigator

Helios Klinikum Erfurt, Erfurt 99089, Germany; Recruiting
Gerald Burgard, MD

Hadassah-Hebrew University Medical Center, Jerusalem 91102, Israel; Recruiting
David Leibowitz, MD

Azienda Ospedaliera Niguarda Ca'Granda, Milano, Italy; Recruiting
Simonetta Passarani, MD

Aga Khan Hospital, Kisumu 40100, Kenya; Recruiting
Farida Kaittany, MD

Aga Khan University Hospital - Nairobi, Nairobi 00508, Kenya; Recruiting
Gerald Yonga, MD PhD

Aminu Kano Teaching Hospital, Kano, Nigeria; Recruiting
Kamilu Karaye, MD

De La Salle University Medical Center, Dasmariñas City 4114, Philippines; Recruiting
Victor Mendoza, MD, Principal Investigator

Philippines General Hospital, Manila 1000, Philippines; Recruiting
Eugenio Reyes, MD

Malopolskie Centrum Medyczne, Krakow 30-510, Poland; Recruiting
Wojciech Szczeklik, MD PhD

University of the Free State, Bloemfontein 9300, South Africa; Recruiting
Johan Diedericks, MD PhD

University of Cape Town, Cape Town, South Africa; Recruiting
Bongani Mayosi, MD, Principal Investigator

Hospital de la Santa Creu I Sant Pau, Barcelona 8025, Spain; Recruiting
Pilar Paniagua-Iglesias, MD, Principal Investigator

Hospital Universatario Valle Hebron, Barcelona 8035, Spain; Recruiting
Miriam de Nadal, MD, Principal Investigator

Hospital Universitario Ramon y Cajal, Madrid 28034, Spain; Recruiting
Ana Serrano, MD

University of Alberta Hospital, Edmonton, Alberta T6G 2P4, Canada; Recruiting
Michael Jacka, MD, Principal Investigator

Instituto Cardiovascular de Buenos Aires, Caba, Buenos Aires 1428, Argentina; Recruiting
Mariano Benzadon, MD

Clinica Coronel Suarez, Coronel Suarez, Buenos Aires B7540GHD, Argentina; Recruiting
Alberto Caccavo, MD PhD

Centro Medico Consultan Salud, Haedo, Buenos Aires B1706AJU, Argentina; Recruiting
Javier Marino, MD

St. Paul Hospital Cavite, Dasmarinas City, Cavite 4114, Philippines; Recruiting
Jose Armand Gurango, MD

Klinikum der J. W. Goethe-Universität Frankfurt, Frankfurt, Hesse 60596, Germany; Recruiting
Kai Zacharowski, MD, Principal Investigator

Kansas University Medical Center, Kansas City, Kansas 66160, United States; Recruiting
Isaac Opole, MD, Principal Investigator

University of Kwazulu-Natal, Congella, Kwazulu-Natal 4013, South Africa; Recruiting
Bruce Biccard, MD

Grey's Hospital, Pietermaritzburg, Kwazulu-Natal 3200, South Africa; Recruiting
Reitze Rodseth, MD

Hospice Civils de Lyon, Pierre Benite, Lyon 69495, France; Recruiting
Vincent Piriou, MD

Manila Doctors Hospital, Ermita, Manila 1000, Philippines; Recruiting
Noemi Pestano, MD, Principal Investigator

Medical Center Manila, Ermita, Manila 1000, Philippines; Recruiting
Roberto Raymundo, MD

Health Sciences Centre Winnipeg, Winnipeg, Manitoba R3A1R9, Canada; Recruiting
Sadeesh Srinathan, MD

Rizal Medical Center, Pasig City, Metro Manila 1600, Philippines; Recruiting
Mariano Lopez, MD

Henry Ford Hospital, Detroit, Michigan 48026, United States; Recruiting
Vinay Shah, MD, Principal Investigator

Concord Repatriation General Hospital, Sydney, New South Wales 2139, Australia; Recruiting
David Brieger, MD PhD

University of Rochester Medical Center, Rochester, New York 14642, United States; Recruiting
Sabu Thomas, MD, Email: mailto:Sabu_Thomas@URMC.Rochester.edu
Sabu Thomas, MD, Principal Investigator

Wake Forest School of Medicine, Winston Salem, North Carolina 27157, United States; Recruiting
Scott Miller, MD

Belfast Health and Social Care Trust, Royal Victoria Hospital, Belfast, North Ireland BT12 6BA, United Kingdom; Recruiting
Martin Shields, MD

Cleveland Clinic, Cleveland, Ohio 44195, United States; Recruiting
Daniel I Sessler, MD, Email: ds@or.org
Daniel I Sessler, MD, Principal Investigator

University Hospitals Case Medical Center, Cleveland, Ohio 44106, United States; Recruiting
Stephan Gravenstein, MD

Ohio State University Wexner Medical Center, Columbus, Ohio 43221, United States; Recruiting
Harrison Weed, MD

Hamilton General Hospital, Hamilton, Ontario L8L 2X2, Canada; Recruiting
Patrick Magloire, MD, Principal Investigator

Juravinski Hospital and Cancer Centre, Hamilton, Ontario L8V 4X2, Canada; Recruiting
Philip J. Devereaux, MD, Phone: 905-527-4322, Ext: 40379, Email: philipj@mcmaster.ca
Vikas Tandon, MD, Principal Investigator
Ameen Patel, MD, Sub-Investigator
Philip J Devereaux, MD PhD, Sub-Investigator

St. Joseph's Healthcare Hamilton, Hamilton, Ontario L8N 4A6, Canada; Recruiting
John Neary, MD, Principal Investigator

Queens University - Kingston General Hospital, Kingston, Ontario K7K2V7, Canada; Recruiting
Jason Erb, MD

University Hospital, London Health Sciences Centre, London, Ontario N6A 5A5, Canada; Recruiting
Marko Mrkobrada, MD, Principal Investigator

Victoria Hospital, London Health Sciences Centre, London, Ontario N6O 5R1, Canada; Recruiting
Amit Garg, MD, MA, PhD, Principal Investigator

Oregon Health and Science University, Portland, Oregon 97239, United States; Recruiting
Avital O'Glasser, MD

PeaceHealth Sacred Heart Medical Center, Springfield, Oregon 97477, United States; Recruiting
Arturo Salazar, MD

Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, United States; Recruiting
Anita Gupta, MD

Centre Hospitalier Universitaire de Montreal - St. Luc Hospital, Montreal, Quebec H2X3J4, Canada; Recruiting
Benoit Deligne, MD

Montreal General Hospital - McGill University Health Centre, Montreal, Quebec H3G1A4, Canada; Recruiting
David Hornstein, MD

Clinica Parra - Centro de Investigaciones, Rafaela, Santa Fe S2300MMA, Argentina; Recruiting
Adrian Ingaramo, MD

Hospital Italiano Garibaldi, Rosario, Santa Fe 2000, Argentina; Recruiting
Luciano Jose Maria Aramberry, MD

Sanatorio Los Arroyos, Rosario, Santa Fe 2000, Argentina; Recruiting
Marcelo Cardona, MD

Sanatorio San Martin, Venado Tuerto, Santa Fe 2600, Argentina; Recruiting
Oscar Gomez Vilamajo, MD

Clinica Foscal, Floridablanca, Santander, Colombia; Recruiting
Gustavo Parra Zuluaga, MD

University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, United States; Recruiting
Juan Cata, MD

Sant'Antonio Hospital, San Daniele Del Friuli, Udine 33038, Italy; Recruiting
Lucio Mos, MD

University of Virginia, Charlottesville, Virginia 22908-0710, United States; Recruiting
Edward Nemergut, MD

Additional Information

Starting date: January 2013
Last updated: January 23, 2015

Page last updated: August 23, 2015

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