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Rationale and design for the myocardial ischemia and transfusion (MINT) randomized clinical trial - 10/02/23

Doi : 10.1016/j.ahj.2022.11.015 
Jeffrey L. Carson, MD a, 1, , Maria Mori Brooks, PhD b, 1, Bernard R. Chaitman, MD c, John H. Alexander, MD MHS d, Shaun G. Goodman, MD MSc e, f, Marnie Bertolet, PhD b, J. Dawn Abbott, MD g, Howard A. Cooper, MD h, Sunil V. Rao, MD i, j, Darrell J. Triulzi, MD k, Dean A. Fergusson, PhD l, William J. Kostis, PhD MD a, Helaine Noveck, MPH a, Tabassome Simon, MD PhD m, Philippe Gabriel Steg, MD n, Andrew P. DeFilippis, MD o, Andrew M. Goldsweig, MD MS p, Renato D. Lopes, MD q, d, Harvey White, DSc r, Caroline Alsweiler, PhD r, Erin Morton, PhD s, Paul C. Hébert, MD MHSc t

on behalf of the MINT Investigators

  Index MINT Investigators from Supplementary Appendix E
Jeffrey L. Carson 1, Shahab Ghafghazi 2, Howard A. Cooper 3, Frances Wood 4, Mark Menegus 5, Barry Uretsky 6, Srikanth Vallurupalli 7, Gregory Maniatis 8, Luis Gruberg 9, Robert Roswell 10, Joseph Rossi 11, Farhad Abtahian 12, Meechai Tessalee 13, Gregory Barsness 14, J. Dawn Abbott 15, Herbert Aronow 16, Kodangudi Ramanathan 17, Mark Schmidhofer 18, Friederike Keating 19, Michael Carson 20, Michael Kontos 21, Mansoor Qureshi 22, Stacey Clegg 23, Warren Laskey 24, Tamar Polonsky 25, Rajesh Gupta 26, Mujeeb Abdul Sheikh 27, Lynne Uhl 28, Paul Mullen 29, Arthur Bracey 30, William Matthai 31, Christopher Stowell 32, David Dudzinski 33, Gregary Marhefka 34, Perry Weinstock 35, William Lawson 36, Norma Keller 37, Eugene Yuriditsky 38, Michael Thomas 39, Alice Jacobs 40, Claudia Hochberg 41, Omar Siddiqi 42, Joshua Schulman-Marcus 43, Mikhail Torosoff 44, Michael Gitter 45, Xuming Dai 46, Jay Traverse 47, Eric McCamant 48, Jason Scott 49, Rajesh Swaminathan 50, Sunil Rao 51, Andrew M. Goldsweig 52, Andrew P. DeFilippis 53, Adam Salisbury 54, David Landers 55, Ganesh Raveendran 56, Ramin Ebrahimi 57, Richard Bach 58, Joseph Delehanty 59, Raj C. Shah 60, Sorin Brener 61, Jonathan Doroshow 62, Adriano Caixeta 63, Dalton Precoma 64, Frederico Toledo Campo Dall'Orto 65, Pedro Beraldo De Andrade 66, Marianna Dracoulakis 67, Lília Nigro Maia 68, Luiz Eduardo Fontelles Ritt 69, Alexandre Quadros 70, Dário Celestino Sobral Filho 71, Fernando De Martino 72, Thao Huynh 73, Greg Schnell 74, Manohara Senaratne 75, Vikas Tandon 76, Vikas Tandon 77, John Neary 78, David Laflamme 79, Jean-Pierre Dery 80, Kevin Bainey 81, Richard Haichin 82, Payam Dehghani 83, Ata Ur Rehman Quraishi 84, Brian J. Potter 85, François Martin Carrier 86, Michael Goldfarb 87, Christopher Fordyce 88, Ying Tung Sia 89, Benoit Daneault 90, Mina Madan 91, Terry McPherson 92, John Ducas 93, Kunal Minhas 94, Neil Brass 95, Akshay Bagai 96, Simon Robinson 97, Vladimír Džavík 98, Razi Khan 99, Nicolas Michaud 100, Gabriel Steg 101, Gregory Ducrocq 102, Etienne Puymirat 103, Gilles Lemesle 104, Emile Ferrari 105, Benoit Lattuca 106, Johanne Silvain 107, Gérald Vanzetto 108, Laura Cetran 109, Thibault Lhermusier 110, Yves Cottin 111, Yann Rosamel 112, Denis Angoulvant 113, Jean Guillaume Dillinger 114, Christophe Thuaire 115, Batric Popovic 116, Eric Durand 117, Claire Bouleti 118, François Roubille 119, Laurent Delorme 120, Ian Crozier 121, Jocelyne Benatar 122, Samraj Nandra 123, Ian Ternouth 124, Nick Fisher 125, David Brieger 126, Graham Hillis 127
1 Rutgers Robert Wood Johnson Medical School (A01), United States Sites 
2 Louisville - University of Louisville (A02), Jewish Hospital (A14), Norton Hospital (A65), United States Sites 
3 Westchester Medical Center (A03), United States Sites 
4 WakeMed Health & Hospitals (A04), United States Sites 
5 Montefiore - Weiler Hospital (A06), Moses Hospital (A23), United States Sites 
6 University of Arkansas Medical Sciences - Central Arkansas Veterans (A07), United States Sites 
7 University of Arkansas Medical Sciences -University of Arkansas Medical (A49), United States Sites 
8 Northwell Hospital System - Staten Island University (A09), United States Sites 
9 Northwell Hospital System - Southside Hospital (A53), United States Sites 
10 Northwell Hospital System - Lenox Hill Hospital (A62), United States Sites 
11 UNC Hospitals (A10), United States Sites 
12 Rochester General Hospital (A11), United States Sites 
13 AdventHealth - Adventist Hinsdale Hospital (A12), Adventist La Grange Hospital (A21), Adventist Bolingbrook (A22), United States Sites 
14 Mayo Clinic (A13), United States Sites 
15 Lifespan - Rhode Island Hospital (A15), United States Sites 
16 Lifespan - The Miriam Hospital (A16), United States Sites 
17 Memphis VA Medical Center (A18), United States Sites 
18 UPMC Presbyterian (A20), United States Sites 
19 University of Vermont Medical (A27), United States Sites 
20 Jersey Shore University Medical (A29), United States Sites 
21 Virginia Commonwealth (A31), United States Sites 
22 St. Joseph Mercy Hospital (A32), United States Sites 
23 University of New Mexico (A33), United States Sites 
24 University of New Mexico (A33), United States Sites 
25 University of Chicago (A34), United States Sites 
26 University of Toledo (A36), United States Sites 
27 University of Toledo (A36), United States Sites 
28 Beth Israel Deaconess (A37), United States Sites 
29 Memorial Hospital at Gulfport (A38), United States Sites 
30 Baylor St Luke's (A39), United States Sites 
31 PENN Presbyterian (A40), United States Sites 
32 Massachusetts General Hospital (A44), United States Sites 
33 Massachusetts General Hospital (A44), United States Sites 
34 Thomas Jefferson University (A45), United States Sites 
35 Cooper University Hospital (A47), United States Sites 
36 Stony Brook University (A48), United States Sites 
37 NYU Langone Medical Center (A51), United States Sites 
38 NYU Langone Medical Center (A51), United States Sites 
39 University of Michigan (A54), United States Sites 
40 Boston Medical Center (A56), United States Sites 
41 Boston Medical Center (A56), United States Sites 
42 Boston Medical Center (A56), United States Sites 
43 Albany Medical College (A57), United States Sites 
44 Albany Medical College (A57), United States Sites 
45 Medical College of Wisconsin (A59), United States Sites 
46 NYP Queens (A60), United States Sites 
47 Minneapolis Heart Institute (Foundation) (A61), United States Sites 
48 Lancaster General (A63), United States Sites 
49 Lancaster General (A63), United States Sites 
50 Durham VA Medical Center (A64), United States Sites 
51 Durham VA Medical Center (A64), United States Sites 
52 University of Nebraska Medical Center (A67), United States Sites 
53 Vanderbilt (A69), United States Sites 
54 Saint Luke's Mid America Heart (A05), United States Sites - Inactive 
55 Hackensack University Medical (A17), United States Sites - Inactive 
56 University of Minnesota (A25), United States Sites - Inactive 
57 UCLA / Veterans Affairs Greater LA (A30), United States Sites - Inactive 
58 Washington University St Louis (A35), United States Sites - Inactive 
59 University of Rochester (A43), United States Sites - Inactive 
60 Rush University Medical Center (A46), United States Sites - Inactive 
61 NYP Brooklyn Methodist (A50), United States Sites - Inactive 
62 Lankenau Medical Center (A66), United States Sites - Inactive 
63 Hospital São Paulo (B01), Brazilian Sites 
64 Sociedade Hospitalar Angelina Caron (B02), Brazilian Sites 
65 Hospital Maternidade e Pronto Socorro Santa Lucia (B04), Brazilian Sites 
66 Santa Casa de Marília (B05), Brazilian Sites 
67 Hospital da Bahia (B06), Brazilian Sites 
68 Hospital de Base de Rio Preto (B07), Brazilian Sites 
69 Hospital Cárdio Pulmonar (B10), Brazilian Sites 
70 Instituto de Cardiologia do RS (B13), Brazilian Sites 
71 Pronto Socorro Cardiológico de Prof. Luiz Tavares (B14), Brazilian Sites 
72 Hospital de Clinicas UFTM (B16), Brazilian Sites 
73 Montreal General Hospital (C01), Canadian Sites 
74 Foothills Medical Centre (C02), Canadian Sites 
75 Grey Nuns Community Hospital (C03), Canadian Sites 
76 Hamilton Health Sciences/St. Joseph's Healthcare Hamilton - Hamilton General Hospital (C04), Canadian Sites 
77 Hamilton Health Sciences/St. Joseph's Healthcare Hamilton - Juravinski Hospital (C29), Canadian Sites 
78 Hamilton Health Sciences/St. Joseph's Healthcare Hamilton - St. Joseph's Healthcare Hamilton (C30), Canadian Sites 
79 Hôpital Charles Lemoyne (C05), Canadian Sites 
80 Quebec Heart and Lung Institute (C06), Canadian Sites 
81 University Of Alberta Hospital (C07), Canadian Sites 
82 Royal Victoria Hospital (C08), Canadian Sites 
83 Regina General Hospital (C09), Canadian Sites 
84 QE II Health Sciences Center (C10), Canadian Sites 
85 Centre Hosp. Universitaire de Montreal (C12), Canadian Sites 
86 Centre Hosp. Universitaire de Montreal (C12), Canadian Sites 
87 Jewish General Hospital (C14), Canadian Sites 
88 Vancouver General Hospital (C15), Canadian Sites 
89 Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-Centre-du-Quebec (C17), Canadian Sites 
90 Centre Hospitalier Sherbrooke (C21), Canadian Sites 
91 Sunnybrook Health Sciences Centre (C22), Canadian Sites 
92 London Health Sciences Centre - Victoria Hospital - LHSC (C11), University Hospital (C23), Canadian Sites 
93 St. Boniface General Hospital (C24), Canadian Sites 
94 St. Boniface General Hospital (C24), Canadian Sites 
95 Royal Alexandra Hospital (C25), Canadian Sites 
96 St. Michael's Hospital (C27), Canadian Sites 
97 Victoria Heart Institute (C28), Canadian Sites 
98 UHN (C31), Canadian Sites 
99 Royal Columbian Hospital (C13), Canadian Sites - Inactive 
100 Hotel Dieu de Levis (C19), Canadian Sites - Inactive 
101 Hôpital BICHAT - APHP (E01), European Union Sites 
102 Hôpital BICHAT - APHP (E01), European Union Sites 
103 HEGP - APHP (E02), European Union Sites 
104 CHRU Lille (E03), European Union Sites 
105 CHU Nice - Hôpital Pasteur (E04), European Union Sites 
106 CHU Caremeau - Nîmes (E05), European Union Sites 
107 Hôpital Pitié Salpétrière - APHP (E06), European Union Sites 
108 Hôpital Michalon - Grenoble (E07), European Union Sites 
109 Hôpital Haut Lévêque - Pessac (E08), European Union Sites 
110 CHU Rangueil - Toulouse (E09), European Union Sites 
111 CHU le Bocage - Dijon (E10), European Union Sites 
112 Centre Hospitalier sud francilien (E11), European Union Sites 
113 CHRU Tours - Hôpital Trousseau (E12), European Union Sites 
114 Hôpital Lariboisière - APHP (E13), European Union Sites 
115 CH Louis Pasteur, Chartres (E14), European Union Sites 
116 CHU Nancy (E15), European Union Sites 
117 CHU de Rouen (E16), European Union Sites 
118 CHU Poitiers (E18), European Union Sites 
119 CHU Arnaud de Villeneuve - Montpellier (E19), European Union Sites 
120 Clinique du pont de chaume - Montauban (E20), European Union Sites 
121 Christchurch Hospital (N01), New Zealand Sites 
122 Auckland Hospital (N02), New Zealand Sites 
123 Whangarei Hospital (N04), New Zealand Sites 
124 Taranaki Hospital (N05), New Zealand Sites 
125 Nelson Hospital (N06), New Zealand Sites 
126 Concord Repatriation General Hospital (V03), Australian Sites 
127 Royal Perth Hospital (V04), Australian Sites 

a Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 
b University of Pittsburgh School of Public Health, Pittsburgh, PA 
c St Louis University School of Medicine, St Louis, MO 
d Duke Clinical Research Institute, Durham, NC 
e St. Michael's Hospital, University of Toronto, Toronto Canada 
f Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada 
g Warren Alpert Medical School. Brown University, Providence, RI 
h Westchester Medical Center, Valhalla, NY 
i Durham VA Medical Center, Durham, NC 
j NYU Langone Health, New York, NY 
k University of Pittsburgh School of Medicine, Pittsburgh, PA 
l Ottawa Hospital Research Institute Ottawa, Ontario, Canada 
m Hopital Saint Antoine, Paris, France 
n Université Paris-Cité, Paris, France 
o Vanderbilt University, Nashville, TN 
p University of Nebraska Medical Center, Omaha, NE 
q Brazilian Clinical Research Institute, São Paulo, Brazil 
r Green Lane Clinical Coordinating Centre Ltd, Auckland, New Zealand 
s Finders University, Adelaide, Australia 
t Centre de Recherche du Centre Hosp. Universitaire de Montréal, Montréal, Québec, Canada 

#Reprint request: Jeffrey L Carson MD, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 08901.Rutgers Robert Wood Johnson Medical SchoolNew BrunswickNJ08901

ABSTRACT

Background

Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (<8 g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy.

Methods

We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin <10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary end point is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary end points include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary end points.

Conclusions

The MINT trial will inform RBC transfusion practice in patients with acute MI.

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