Myocardial Injury After Noncardiac Surgery (MINS)Phase 3MANAGENCT01661101
Management of Myocardial Injury After Noncardiac Surgery Trial
A Phase 3 study testing Dabigatran and Omeprazole in people with Myocardial Injury After Noncardiac Surgery (MINS), run by Population Health Research Institute at 82 sites in 19 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Myocardial Injury After Noncardiac Surgery (MINS)
- What is being tested?
- Dabigatran and Omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,754 participants
- Where
- 82 sitesin 19 countries
- Study dates
- Jan 2013to 1 Mar 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
Show all 22Show fewer
- 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.
Trial locations and contacts
82 sites in 19 countries.
82 sites in 19 countries
Canada11 sites
University of Alberta Hospital
Edmonton, Alberta, T6G 2P4
Grey Nuns Hospital
Edmonton, Alberta, T6R 3G8
Hamilton General Hospital
Hamilton, Ontario, L8L 2X2
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
Juravinski Hospital and Cancer Centre
Hamilton, Ontario, L8V 4X2
Queens University - Kingston General Hospital
Kingston, Ontario, K7K2V7
University Hospital, London Health Sciences Centre
London, Ontario, N6A 5A5
Victoria Hospital, London Health Sciences Centre
London, Ontario, N6O 5R1
Centre Hospitalier Universitaire de Montreal - St. Luc Hospital
Montreal, Quebec, H2X3J4
Montreal General Hospital - McGill University Health Centre
Montreal, Quebec, H3G1A4
Health Sciences Centre Winnipeg
Winnipeg, Manitoba, R3A1R9
Poland10 sites
SPZOZ Szpital Powiatowy w Bochni
Bochnia
Spzoz w Brzesku
Brzesko
Malopolskie Centrum Medyczne
Krakow, 30-510
OrtoMed sp. Z.o.o.
Krakow
Samodzielny Publiczny Zakład Opieki
Krakow
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
Krakow
Szpital św. Anny w Miechowie
Miechów
Spzoz w Myslenicach
Myślenice
Specjalistyczny Szpital im. E. Szczeklika
Tarnów, 33-100
Zakład Opieki Zdrowotnej im. Jana Pawła II
Włoszczowa
India9 sites
M.S. Ramaiah Medical College & Hospitals
Bangalore
Narayana Hrudayalaya
Bengaluru
Sidhu Hospital
Dorāha, Distt- Ludhiana, 141421
Amrita Institute of Medical Sciences and Research Institute
Kochi, Kerala
M.V. Hospital & Research Centre
Lucknow
Christian Medical College
Ludhiana
Rahate Surgical Hospital
Nagpur
Surat Institute of Digestive Sciences
Surat, Gujarat, 395002
Ramana Maharishi Rangammal Hospital
Tiruvannamalai
United States7 sites
VA Western New York Healthcare System
Buffalo, New York, 14215
VA North Texas Health Care System Dallas VA Medical Center
Dallas, Texas, 75216
Kansas University Medical Center
Kansas City, Kansas, 66160
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19102
Oregon Health and Science University
Portland, Oregon, 97239
University of Rochester Medical Center
Rochester, New York, 14642
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157
Brazil6 sites
Hospital Lifecenter
Belo Horizonte, 30110-921
Sociendade Hospitalar Angelina Caron
Campina Grande do Sul, Paraná, 83430
Hospital e Maternidade Celso Pierro - PUCCAMP
Campinas, 13060-904
Hospital Maternidade
Poços de Caldas, Minas Gerais, 50761160
Hospital Barra D'Or
Rio de Janeiro, 22775-002
Hospital de Base
São José do Rio Preto, 15090-000
Denmark6 sites
Bispebjerg Hospital, University of Copenhagen
Copenhagen, 2400
Copenhagen University Hospital, Rigshospitalet
Copenhagen
Herlev Hospital
Herlev, 2730
Nordsjaellands Hospital
Hillerød, 3400
Koege-Roskilde Hospital
Køge
Vejle Hospital
Vejle, 7100
Argentina5 sites
Favaloro Foundation
Buenos Aires, C1093AAS
Instituto Cardiovascular de Buenos Aires
Caba, Buenos Aires, 1428
Hospital San Roque
Córdoba, 5000
Clinica Parra - Centro de Investigaciones
Rafaela, Santa Fe Province, S2300MMA
Sanatorio San Martin
Venado Tuerto, Santa Fe Province, 2600
Italy5 sites
Azienda Ospedaliera Niguarda Ca'Granda
Milan
IRCCS Istituto Ortopedico Galeazzi Milan
Milan
IRCCS San Raffaele Scientific Institute
Milan
Ospedale San Gerardo
Monza, 20900
Sant'Antonio Hospital
San Daniele del Friuli, Udine, 33038
South Africa4 sites
University of the Free State
Bloemfontein, 9300
University of Cape Town
Cape Town
University of Kwazulu-Natal
KwaKhangela, KwaZulu-Natal, 4013
Grey's Hospital
Pietermaritzburg, KwaZulu-Natal, 3200
Spain4 sites
Bellvitge University Hospital
Barcelona, 08907
Hospital de la Santa Creu I Sant Pau
Barcelona, 8025
Hospital Universatario Valle Hebron
Barcelona, 8035
Hospital Universitario Ramon y Cajal
Madrid, 28034
Colombia2 sites
Fundacion Cardioinfantil - Instituto de Cardiologia
Bogotá
Clinica Foscal
Floridablanca, Santander Department
Czechia2 sites
Liberec Regional Hospital
Liberec
University Hospital Motol
Motol, 150 06
France2 sites
Hospitalier Pitie Salpetriere
Paris, 75013
Hospice Civils de Lyon
Pierre-Bénite, Lyon, 69495
Germany2 sites
Universitätsklinikum Bonn
Bonn, 53105
Klinikum der J. W. Goethe-Universität Frankfurt
Frankfurt am Main, Hesse, 60596
Philippines2 sites
De La Salle University Medical Center
Dasmariñas, 4114
Philippines General Hospital
Manila, 1000
United Kingdom2 sites
Belfast Health and Social Care Trust, Royal Victoria Hospital
Belfast, North Ireland, BT12 6BA
Russell Halls Hospital, Dudley Group NHS
Dudley
About this study
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
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.
Read the 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.
- Being tested
- Dabigatran, Placebo (for Dabigatran), Omeprazole, Placebo (for Omeprazole)
- Keywords
- Perioperative myocardial infarction, Myocardial injury, noncardiac surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DabigatranDrug
Also called Pradaxa
Dabigatran 110 mg taken twice daily
Placebo (for Dabigatran)Drug
Dabigatran placebo taken twice daily
OmeprazoleDrug
Also called Prilosec, Zegerid
Omeprazole 20 mg capsule taken once daily
Placebo (for Omeprazole)Drug
Omeprazole placebo taken once daily
| Study group | Role | What they receive |
|---|---|---|
| Dabigatran | Experimental | Dabigatran 110 mg capsule taken twice daily Receives: Drug: Dabigatran |
| Omeprazole | Experimental | Omeprazole 20 mg capsule taken once daily Receives: Drug: Omeprazole |
| Placebo (dabigatran) | Placebo comparator | Dabigatran placebo taken twice daily Receives: Drug: Placebo (for Dabigatran) |
| Placebo (omeprazole) | Placebo comparator | Omeprazole placebo taken once daily Receives: Drug: Placebo (for Omeprazole) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Average of 1 year follow-up
Secondary outcomes (6)
Individual secondary outcomes for Dabigatran
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.
Measured: Average of 1 year follow-up
Upper gastrointestinal complication for Omeprazole
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.
Measured: Average of 1 year follow-up
Major vascular complication for Omeprazole
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).
Measured: Average of 1 year follow-up
Individual secondary outcomes for Omeprazole
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.
Measured: Average of 1 year follow-up
Safety outcomes for Dabigatran
- A composite of the number of patients suffering life-threatening bleeding, major bleeding, and critical organ bleeding (i.e., intracranial, intraocular, intraspinal, pericardial, retroperitoneal).
- 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.
Measured: Average of 1 year follow-up
Safety outcomes for Omeprazole
The number of patients suffering Clostridium difficile-associated diarrhea, diarrhea, community-acquired pneumonia, and fractures.
Measured: Average of 1 year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2012 (estimated)
- Study startJan 2013
- Primary completion1 Mar 2018
- Study completion1 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Myocardial Injury After Noncardiac Surgery (MINS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,754 participants (actual)
Sponsor and investigators
- Lead sponsor
- Population Health Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, P.J. Devereaux, Population Health Research Institute
- Investigators
- P.J. Devereaux, MD, PhD, Principal investigator, Population Health Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01661101
- Sponsor's protocol ID
- 1160.143
- Other IDs
- 2011-006056-37
- Acronym
- MANAGE
- Status last verified
- Mar 2018
- First submitted
- 7 Aug 2012
- Last updated
- 26 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 29398173Lamy 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.
PubMed 34308517Devereaux 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.
PubMed 29900874
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01661101
- Acronym / sponsor ID
- MANAGE / 1160.143
- Keywords
- Perioperative myocardial infarction, Myocardial injury, noncardiac surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,754 participants (actual)
- Lead sponsor
- Population Health Research InstituteUniversity, hospital or other
- Study start
- Jan 2013 (actual)
- Primary completion
- 1 Mar 2018 (actual)
- Study completion
- 1 Mar 2018 (actual)
- First posted
- 9 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dabigatran | Experimental | Drug: DabigatranDabigatran 110 mg capsule taken twice daily |
| Omeprazole | Experimental | Drug: OmeprazoleOmeprazole 20 mg capsule taken once daily |
| Placebo (dabigatran) | Placebo comparator | Drug: Placebo (for Dabigatran)Dabigatran placebo taken twice daily |
| Placebo (omeprazole) | Placebo comparator | Drug: Placebo (for Omeprazole)Omeprazole placebo taken once daily |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (22 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DabigatranAlso: PradaxaDabigatran 110 mg taken twice daily | Drug | Dabigatran |
| Placebo (for Dabigatran)Dabigatran placebo taken twice daily | Drug | Placebo (dabigatran) |
| OmeprazoleAlso: Prilosec, ZegeridOmeprazole 20 mg capsule taken once daily | Drug | Omeprazole |
| Placebo (for Omeprazole)Omeprazole placebo taken once daily | Drug | Placebo (omeprazole) |
Primary outcome
Major vascular complication (for Dabigatran)
Time frame: Average of 1 year follow-up
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).
Major upper gastrointestinal complication (for Omeprazole)
Time frame: Average of 1 year follow-up
A composite of the number of patients suffering overt gastroduodenal bleeding, overt upper gastrointestinal bleeding of unknown origin, or upper gastrointestinal perforation.
6 secondary outcomes
Individual secondary outcomes for Dabigatran
Time frame: Average of 1 year follow-up
Upper gastrointestinal complication for Omeprazole
Time frame: Average of 1 year follow-up
Major vascular complication for Omeprazole
Time frame: Average of 1 year follow-up
Individual secondary outcomes for Omeprazole
Time frame: Average of 1 year follow-up
Safety outcomes for Dabigatran
Time frame: Average of 1 year follow-up
Safety outcomes for Omeprazole
Time frame: Average of 1 year follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2018.
- Background: PubMed 29398173Duceppe 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.
- Derived from this study: PubMed 34308517Lamy 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.
- Derived from this study: PubMed 29900874Devereaux 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
P.J. Devereaux, MD, PhD principal investigator
Population Health Research Institute
82 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dabigatran and Omeprazole in people with Myocardial Injury After Noncardiac Surgery (MINS), run by Population Health Research Institute at 82 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 82 sites in Canada, Poland, India, United States, Brazil and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major vascular complication (for Dabigatran) (time frame: Average of 1 year follow-up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01661101, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2018.