Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)

Emmanuelle Duceppe; Salim Yusuf; Vikas Tandon; Reitze Rodseth; Bruce M Biccard; Denis Xavier; Wojciech Szczeklik; Christian S Meyhoff; Maria Grazia Franzosi; Jessica Vincent; Sadeesh K Srinathan; Joel Parlow; Patrick Magloire; John Neary; Mangala Rao; Navneet K Chaudhry; Bongani Mayosi; Miriam de Nadal; Ekaterine Popova; Juan Carlos Villar; Fernando Botto; Otavio Berwanger; Gordon Guyatt; John W Eikelboom; Daniel I Sessler; Clive Kearon; Shirley Pettit; Stuart J Connolly; Mukul Sharma; Shrikant I Bangdiwala; P J Devereaux

doi:10.1016/j.cjca.2018.01.020

Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)

Emmanuelle Duceppe, Salim Yusuf, Vikas Tandon, Reitze Rodseth, Bruce M Biccard, Denis Xavier, Wojciech Szczeklik, Christian S Meyhoff, Maria Grazia Franzosi, Jessica Vincent, Sadeesh K Srinathan, Joel Parlow, Patrick Magloire, John Neary, Mangala Rao, Navneet K Chaudhry, Bongani Mayosi, Miriam de Nadal, Ekaterine Popova, Juan Carlos VillarFernando Botto, Otavio Berwanger, Gordon Guyatt, John W Eikelboom, Daniel I Sessler, Clive Kearon, Shirley Pettit, Stuart J Connolly, Mukul Sharma, Shrikant I Bangdiwala, P J Devereaux

Institut for Klinisk Medicin

18 Citationer (Scopus)

Abstract

BACKGROUND: Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS.

METHODS: The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients.

RESULTS: The trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants.

CONCLUSION: MANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS.

Originalsprog	Engelsk
Tidsskrift	Canadian Journal of Cardiology
Vol/bind	34
Udgave nummer	3
Sider (fra-til)	295-302
ISSN	0828-282X
DOI	https://doi.org/10.1016/j.cjca.2018.01.020
Status	Udgivet - mar. 2018

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10.1016/j.cjca.2018.01.020

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Duceppe, E., Yusuf, S., Tandon, V., Rodseth, R., Biccard, B. M., Xavier, D., Szczeklik, W., Meyhoff, C. S., Franzosi, M. G., Vincent, J., Srinathan, S. K., Parlow, J., Magloire, P., Neary, J., Rao, M., Chaudhry, N. K., Mayosi, B., de Nadal, M., Popova, E., ... Devereaux, P. J. (2018). Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE). Canadian Journal of Cardiology, 34(3), 295-302. https://doi.org/10.1016/j.cjca.2018.01.020

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 2018, 'Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)', Canadian Journal of Cardiology, bind 34, nr. 3, s. 295-302. https://doi.org/10.1016/j.cjca.2018.01.020

@article{1dc8e242a42b4b4b82d9c20102d79705,

title = "Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)",

abstract = "BACKGROUND: Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS.METHODS: The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients.RESULTS: The trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants.CONCLUSION: MANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS.",

keywords = "Aged, Cause of Death, Dabigatran/therapeutic use, Double-Blind Method, Female, Follow-Up Studies, Humans, Internationality, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction/drug therapy, Omeprazole/therapeutic use, Postoperative Complications/epidemiology, Proportional Hazards Models, Risk Assessment, Surgical Procedures, Operative/adverse effects, Survival Analysis, Treatment Outcome",

author = "Emmanuelle Duceppe and Salim Yusuf and Vikas Tandon and Reitze Rodseth and Biccard, {Bruce M} and Denis Xavier and Wojciech Szczeklik and Meyhoff, {Christian S} and Franzosi, {Maria Grazia} and Jessica Vincent and Srinathan, {Sadeesh K} and Joel Parlow and Patrick Magloire and John Neary and Mangala Rao and Chaudhry, {Navneet K} and Bongani Mayosi and {de Nadal}, Miriam and Ekaterine Popova and Villar, {Juan Carlos} and Fernando Botto and Otavio Berwanger and Gordon Guyatt and Eikelboom, {John W} and Sessler, {Daniel I} and Clive Kearon and Shirley Pettit and Connolly, {Stuart J} and Mukul Sharma and Bangdiwala, {Shrikant I} and Devereaux, {P J}",

year = "2018",

month = mar,

doi = "10.1016/j.cjca.2018.01.020",

language = "English",

volume = "34",

pages = "295--302",

journal = "Canadian Journal of Cardiology",

issn = "0828-282X",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)

AU - Duceppe, Emmanuelle

AU - Yusuf, Salim

AU - Tandon, Vikas

AU - Rodseth, Reitze

AU - Biccard, Bruce M

AU - Xavier, Denis

AU - Szczeklik, Wojciech

AU - Meyhoff, Christian S

AU - Franzosi, Maria Grazia

AU - Vincent, Jessica

AU - Srinathan, Sadeesh K

AU - Parlow, Joel

AU - Magloire, Patrick

AU - Neary, John

AU - Rao, Mangala

AU - Chaudhry, Navneet K

AU - Mayosi, Bongani

AU - de Nadal, Miriam

AU - Popova, Ekaterine

AU - Villar, Juan Carlos

AU - Botto, Fernando

AU - Berwanger, Otavio

AU - Guyatt, Gordon

AU - Eikelboom, John W

AU - Sessler, Daniel I

AU - Kearon, Clive

AU - Pettit, Shirley

AU - Connolly, Stuart J

AU - Sharma, Mukul

AU - Bangdiwala, Shrikant I

AU - Devereaux, P J

PY - 2018/3

Y1 - 2018/3

N2 - BACKGROUND: Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS.METHODS: The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients.RESULTS: The trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants.CONCLUSION: MANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS.

AB - BACKGROUND: Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS.METHODS: The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients.RESULTS: The trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants.CONCLUSION: MANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS.

KW - Aged

KW - Cause of Death

KW - Dabigatran/therapeutic use

KW - Double-Blind Method

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Internationality

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Myocardial Infarction/drug therapy

KW - Omeprazole/therapeutic use

KW - Postoperative Complications/epidemiology

KW - Proportional Hazards Models

KW - Risk Assessment

KW - Surgical Procedures, Operative/adverse effects

KW - Survival Analysis

KW - Treatment Outcome

U2 - 10.1016/j.cjca.2018.01.020

DO - 10.1016/j.cjca.2018.01.020

M3 - Journal article

C2 - 29398173

SN - 0828-282X

VL - 34

SP - 295

EP - 302

JO - Canadian Journal of Cardiology

JF - Canadian Journal of Cardiology

IS - 3

ER -

Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)

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