Management of Myocardial Injury After Noncardiac Surgery Trial

NCT01661101 | Completed Phase 3 DMC

• 2 other identifiers: 1160.1432011-006056-37
• Study Type: interventional
• Target: 1,754
• Locations: 19 countries
• Sites: 82

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.

Conditions

Myocardial Injury After Noncardiac Surgery (MINS)

Keywords

Perioperative myocardial infarction; Myocardial injury; noncardiac surgery

Outcome Measures

Primary Outcomes (2)

• Major vascular complication (for Dabigatran)

  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).

  Average of 1 year follow-up

• Major upper gastrointestinal complication (for Omeprazole)

  A composite of the number of patients suffering overt gastroduodenal bleeding, overt upper gastrointestinal bleeding of unknown origin, or upper gastrointestinal perforation.

  Average of 1 year follow-up

Secondary Outcomes (6)

• Individual secondary outcomes for Dabigatran

  Average of 1 year follow-up

• Upper gastrointestinal complication for Omeprazole

  Average of 1 year follow-up

• Major vascular complication for Omeprazole

  Average of 1 year follow-up

• Individual secondary outcomes for Omeprazole

  Average of 1 year follow-up

• Safety outcomes for Dabigatran

  Average of 1 year follow-up

Study Arms (4)

Dabigatran

EXPERIMENTAL

Dabigatran 110 mg capsule taken twice daily

Drug: Dabigatran

Omeprazole

EXPERIMENTAL

Omeprazole 20 mg capsule taken once daily

Drug: Omeprazole

Placebo (dabigatran)

PLACEBO COMPARATOR

Dabigatran placebo taken twice daily

Drug: Placebo (for Dabigatran)

Placebo (omeprazole)

PLACEBO COMPARATOR

Omeprazole placebo taken once daily

Drug: Placebo (for Omeprazole)

Interventions

Dabigatran DRUG

Dabigatran 110 mg taken twice daily

Also known as: Pradaxa

Dabigatran

Placebo (for Dabigatran) DRUG

Dabigatran placebo taken twice daily

Placebo (dabigatran)

Omeprazole DRUG

Omeprazole 20 mg capsule taken once daily

Also known as: Prilosec, Zegerid

Omeprazole

Placebo (for Omeprazole) DRUG

Omeprazole placebo taken once daily

Placebo (omeprazole)

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Population Health Research Institute: lead

Study Sites (82)

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

VA Western New York Healthcare System

Buffalo, New York, 14215, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

VA North Texas Health Care System Dallas VA Medical Center

Dallas, Texas, 75216, United States

Location

Instituto Cardiovascular de Buenos Aires

Caba, Buenos Aires, 1428, Argentina

Location

Clinica Parra - Centro de Investigaciones

Rafaela, Santa Fe Province, S2300MMA, Argentina

Location

Sanatorio San Martin

Venado Tuerto, Santa Fe Province, 2600, Argentina

Location

Favaloro Foundation

Buenos Aires, C1093AAS, Argentina

Location

Hospital San Roque

Córdoba, 5000, Argentina

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Hospital Maternidade

Poços de Caldas, Minas Gerais, 50761160, Brazil

Location

Sociendade Hospitalar Angelina Caron

Campina Grande do Sul, Paraná, 83430, Brazil

Location

Hospital Lifecenter

Belo Horizonte, 30110-921, Brazil

Location

Hospital e Maternidade Celso Pierro - PUCCAMP

Campinas, 13060-904, Brazil

Location

Hospital Barra D'Or

Rio de Janeiro, 22775-002, Brazil

Location

Hospital de Base

São José do Rio Preto, 15090-000, Brazil

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2P4, Canada

Location

Grey Nuns Hospital

Edmonton, Alberta, T6R 3G8, Canada

Location

Health Sciences Centre Winnipeg

Winnipeg, Manitoba, R3A1R9, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Juravinski Hospital and Cancer Centre

Hamilton, Ontario, L8V 4X2, Canada

Location

Queens University - Kingston General Hospital

Kingston, Ontario, K7K2V7, Canada

Location

University Hospital, London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Victoria Hospital, London Health Sciences Centre

London, Ontario, N6O 5R1, Canada

Location

Centre Hospitalier Universitaire de Montreal - St. Luc Hospital

Montreal, Quebec, H2X3J4, Canada

Location

Montreal General Hospital - McGill University Health Centre

Montreal, Quebec, H3G1A4, Canada

Location

Clinica Foscal

Floridablanca, Santander Department, Colombia

Location

Fundacion Cardioinfantil - Instituto de Cardiologia

Bogotá, Colombia

Location

Liberec Regional Hospital

Liberec, Czechia

Location

University Hospital Motol

Motol, 150 06, Czechia

Location

Bispebjerg Hospital, University of Copenhagen

Copenhagen, 2400, Denmark

Location

Copenhagen University Hospital, Rigshospitalet

Copenhagen, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Nordsjaellands Hospital

Hillerød, 3400, Denmark

Location

Koege-Roskilde Hospital

Køge, Denmark

Location

Vejle Hospital

Vejle, 7100, Denmark

Location

Hospice Civils de Lyon

Pierre-Bénite, Lyon, 69495, France

Location

Hospitalier Pitie Salpetriere

Paris, 75013, France

Location

Klinikum der J. W. Goethe-Universität Frankfurt

Frankfurt am Main, Hesse, 60596, Germany

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Sidhu Hospital

Dorāha, Distt- Ludhiana, 141421, India

Location

Surat Institute of Digestive Sciences

Surat, Gujarat, 395002, India

Location

Amrita Institute of Medical Sciences and Research Institute

Kochi, Kerala, India

Location

M.S. Ramaiah Medical College & Hospitals

Bangalore, India

Location

Narayana Hrudayalaya

Bengaluru, India

Location

M.V. Hospital & Research Centre

Lucknow, India

Location

Christian Medical College

Ludhiana, India

Location

Rahate Surgical Hospital

Nagpur, India

Location

Ramana Maharishi Rangammal Hospital

Tiruvannamalai, India

Location

Sant'Antonio Hospital

San Daniele del Friuli, Udine, 33038, Italy

Location

Azienda Ospedaliera Niguarda Ca'Granda

Milan, Italy

Location

IRCCS Istituto Ortopedico Galeazzi Milan

Milan, Italy

Location

IRCCS San Raffaele Scientific Institute

Milan, Italy

Location

Ospedale San Gerardo

Monza, 20900, Italy

Location

Aga Khan University Hospital - Nairobi

Nairobi, 00508, Kenya

Location

Hospital Nacional Cayetano Heredia

Lima, Peru

Location

De La Salle University Medical Center

Dasmariñas, 4114, Philippines

Location

Philippines General Hospital

Manila, 1000, Philippines

Location

SPZOZ Szpital Powiatowy w Bochni

Bochnia, Poland

Location

Spzoz w Brzesku

Brzesko, Poland

Location

Malopolskie Centrum Medyczne

Krakow, 30-510, Poland

Location

OrtoMed sp. Z.o.o.

Krakow, Poland

Location

Samodzielny Publiczny Zakład Opieki

Krakow, Poland

Location

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie

Krakow, Poland

Location

Szpital św. Anny w Miechowie

Miechów, Poland

Location

Spzoz w Myslenicach

Myślenice, Poland

Location

Specjalistyczny Szpital im. E. Szczeklika

Tarnów, 33-100, Poland

Location

Zakład Opieki Zdrowotnej im. Jana Pawła II

Włoszczowa, Poland

Location

University of Kwazulu-Natal

KwaKhangela, KwaZulu-Natal, 4013, South Africa

Location

Grey's Hospital

Pietermaritzburg, KwaZulu-Natal, 3200, South Africa

Location

University of the Free State

Bloemfontein, 9300, South Africa

Location

University of Cape Town

Cape Town, South Africa

Location

Bellvitge University Hospital

Barcelona, 08907, Spain

Location

Hospital de la Santa Creu I Sant Pau

Barcelona, 8025, Spain

Location

Hospital Universatario Valle Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Belfast Health and Social Care Trust, Royal Victoria Hospital

Belfast, North Ireland, BT12 6BA, United Kingdom

Location

Russell Halls Hospital, Dudley Group NHS

Dudley, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 29398173 BACKGROUND

• 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.

  PMID: 34308517 DERIVED

• 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.

  PMID: 29900874 DERIVED

MeSH Terms

Interventions

Dabigatran; Omeprazole; omeprazole, sodium bicarbonate drug combination

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals

Study Officials

• P.J. Devereaux, MD, PhD

  Population Health Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine (Cardiology) and Clinical Epidemiology and Biostatistics, McMaster University

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 9, 2012
• Study Start: January 1, 2013
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: March 26, 2018

Record last verified: 2018-03

Locations

DE (2); PH (2); CO (2); AR (5); KE (1); ZA (4); GB (2); US (7); FR (2); ES (4); BR (6); CZ (2); PL (10); IN (9); DK (6); IT (5); AU (1); PE (1); CA (11)