AzTrials
AzTrials

Cardiovascular DiseasePhase 3CIRTNCT01594333

Cardiovascular Inflammation Reduction Trial

A Phase 3 study testing Methotrexate in people with Cardiovascular Disease, run by Brigham and Women's Hospital at 470 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The Cardiovascular Inflammation Reduction Trial (CIRT) is a randomized clinical trial investigating whether taking low-dose methotrexate reduces heart attacks, strokes, or death in people with type 2 diabetes or metabolic syndrome that have had a heart attack or multiple coronary blockages. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cardiovascular Disease
What is being tested?
Methotrexate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
4,786 participants
Where
470 sitesin 3 countries
Study dates
Apr 2013to 30 Oct 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years at screening
  • Documented past history of myocardial infarction OR past evidence of multivessel coronary artery disease by angiography.
  • To qualify on the basis of past history of myocardial infarction, the event must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening.
  • To qualify on the basis of multivessel coronary disease, there must be past angiographic evidence of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening.
  • History of type 2 diabetes or metabolic syndrome at time of study enrollment
  • Willingness to participate as evidenced by signing the study informed consent

Who cannot join

  • Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years;
  • Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease
  • White blood cell count < 3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul
  • Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN);
  • Creatinine clearance < 40 ml/min as estimated with the Cockcroft-Gault equation;
  • History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week
Show all 13Show fewer
  • Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed.
  • Men who plan to father children during the study period or who are unwilling to use effective forms of contraception.
  • Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible;
  • Current indication for methotrexate therapy;
  • Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions.
  • Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol.
  • New York Heart Association Class IV congestive heart failure.

Trial locations and contacts

470 sites in 3 countries.

366 sites in 3 countries

United States300 sites

  • Center for Clinical Res. Abington Health

    Abington, Pennsylvania, 19001

  • Akron General Medical Center

    Akron, Ohio, 44307

  • Albany Medical College

    Albany, New York, 12208

  • Albany Stratton VA Medical Center

    Albany, New York, 12208

  • Presbyterian Heart Group

    Albuquerque, New Mexico, 87106

  • Endeavor Medical Research

    Alpena, Michigan, 49707

  • Oracle Clinical Research, Inc.

    Anaheim, California, 92801

  • Northwest Heart Clinical Research

    Arlington Heights, Illinois, 60005

  • Clinical Study Center of Asheville

    Asheville, North Carolina, 28801

  • Athens Regional Medical Center

    Athens, Georgia, 30606

  • Ohio University Heritage College of Osteopathic Medicine

    Athens, Ohio, 45701

  • Atlanta Veterans Affairs Medical Center

    Atlanta, Georgia, 30033

  • Laureate Medical Group at Northside

    Atlanta, Georgia, 30308

  • Synergy Therapeutic Partners

    Atlanta, Georgia, 30308

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Maine Research Associates

    Auburn, Maine, 04210

  • Avant Research Associates LLC

    Austin, Texas, 78704

  • Texas Heart and Vascular Research, LLC

    Austin, Texas, 78745

  • Pianko - Aventura Research Center, LLC

    Aventura, Florida, 33180

  • Sinai Center for Thrombosis Research

    Baltimore, Maryland, 21215

  • Paul A. Shapero, M.D.

    Bangor, Maine, 04401

  • Southeast TX Clinical Research Center

    Beaumont, Texas, 77702

  • St. Luke's University Hospital

    Bethlehem, Pennsylvania, 18018

  • Southern Maine Health Care

    Biddeford, Maine, 04005

  • Cornerstone Family Medicine

    Big Spring, Texas, 79720

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • North Ridge Heart Associates

    Boca Raton, Florida, 33434

  • St. Luke's Idaho Cardiology Associates

    Boise, Idaho, 83712

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • St. Elizabeth's Medical Center

    Boston, Massachusetts, 02135

  • MGH Cardiology

    Boston, Massachusetts, 02214

  • Joslin Diabetes Center

    Boston, Massachusetts, 02215

  • Connecticut Heart and Vascular Center

    Bridgeport, Connecticut, 06606

  • Bridgeport Hospital

    Bridgeport, Connecticut, 06610

  • Center for Advanced Medicine and Research LLC

    Bridgeton, Missouri, 63044

  • Renu-Ca Research Institute, Lower Bucks Hospital

    Bristol, Pennsylvania, 19007

  • Brown - SUNY Downstate Medical Center

    Brooklyn, New York, 11203

  • Main Line Health Center, Broomall

    Broomall, Pennsylvania, 19008

  • Buffalo Heart Group

    Buffalo, New York, 14215

  • Burke Internal Medicine & Research

    Burke, Virginia, 22015

  • Lahey Hospital and Medical Center

    Burlington, Massachusetts, 01805

  • Spirit Physician Services, Inc

    Camp Hill, Pennsylvania, 17011

  • Diabetes and Endocrinology Associates of Stark Cit

    Canton, Ohio, 44718

  • IMD Medical Center

    Carrollton, Texas, 75006

  • Texas Health Physicians Group

    Carrollton, Texas, 75010

  • The Chambersburg Hospital

    Chambersburg, Pennsylvania, 17201

  • Metrolina Internal Medicine

    Charlotte, North Carolina, 28204

  • Gaffney Health Services

    Charlotte, North Carolina, 28205

  • Carolinas Research Center

    Charlotte, North Carolina, 28215

  • St. Mary's Medical Center

    Charlotte Hall, Maryland, 20622

  • New Phase Research & Development

    Chattanooga, Tennessee, 37409

  • Massachusetts General Hospital - Chelsea Health Care Center

    Chelsea, Massachusetts, 02150

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Advocate Med Group-Heart & Vascular Of Illinois

    Chicago, Illinois, 60657

  • The Lindner Research Center

    Cincinnati, Ohio, 45219

  • Center for Advanced Medicine and Research

    City of Saint Peters, Missouri, 63303

  • St. Francis Medical Institute

    Clearwater, Florida, 33765

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Calvert Memorial Hospital

    Clinton, Maryland, 20735

  • Munni R. Selagamsetty, Md, Pc

    Colorado Springs, Colorado, 80910

  • Clinical Research Center University of Missouri

    Columbia, Missouri, 65212

  • South Carolina Heart Center

    Columbia, South Carolina, 29204

  • Amistad Research Center, LLC

    Columbia, South Carolina, 29223

  • Optimed Research, LTD

    Columbus, Ohio, 43235

  • Bassett Healthcare Network

    Cooperstown, New York, 13326

  • Gonzalez MD & Aswad MD Health Ser

    Coral Gables, Florida, 33134

  • NYU Hudson Valley Cardiology

    Cortlandt Manor, New York, 10567

  • Samaritan Health Services

    Corvallis, Oregon, 97330

  • Heart Vascular of Northern Arizona

    Cottonwood, Arizona, 86326

  • Dorothy H. Banish, MD, APMC Study Group

    Covington, Louisiana, 70433

  • Avant Research Associates, LLC

    Crowley, Louisiana, 70526

  • Medical Group of Culver City

    Culver City, California, 90230

  • Partners in Clinical Research

    Cumberland, Rhode Island, 02864

  • Atlanta Heart Specialists, LLC

    Cumming, Georgia, 30041

  • American Research Institute, Inc.

    Cutler Bay, Florida, 33157

  • Cardiovascular Research Institute of Dallas

    Dallas, Texas, 75231

  • North Texas Health Center

    Dallas, Texas, 75231

  • The Heart Center of Dallas

    Dallas, Texas, 75235

  • Heart and Rhythm Specialists

    Dalton, Georgia, 30720

  • Dayton Heart Center

    Dayton, Ohio, 45414

  • Dayton Veteran Affairs Medical Center

    Dayton, Ohio, 45428

  • Daytona Heart Group

    Daytona Beach, Florida, 32114

  • Daytona Heart Group

    DeLand, Florida, 32720

  • Seidman Clinical Trials

    Delray Beach, Florida, 33484

  • Steven Cohen MD

    Delray Beach, Florida, 33484

  • Vijay - Aurora Denver Cardiology

    Denver, Colorado, 80218

  • Global Medical Research

    DeSoto, Texas, 75115

  • John D. Dingell Veterans Affairs Medical Center

    Detroit, Michigan, 48201

  • Trace Research Group at Wayne State University

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Infinite Clinical Research

    Doral, Florida, 33126

  • International Research Partners, LLC

    Doral, Florida, 33166

  • Medical Research Institute at Doral, Inc.

    Doral, Florida, 33178

  • Central Bucks Cardiology

    Doylestown, Pennsylvania, 18901

  • Altoona Center for Clinical Research

    Duncansville, Pennsylvania, 16635

  • Albert F. Johary MD, PC

    Dunwoody, Georgia, 30338

  • Cardiospecialists, LTD

    Dyer, Indiana, 46311

  • Eastern Carolina Cardiovascular, PA

    Elizabeth City, North Carolina, 27909

  • Heart Specialists of Lancaster County

    Ephrata, Pennsylvania, 17522

  • Saint Vincent Consultants in Cardiovascular Diseases, LLC

    Erie, Pennsylvania, 16502

  • Lake Internal Medicine Assocaties

    Eustis, Florida, 32726

  • Martin - Martin Family Practice and Research

    Evansville, Indiana, 47714

  • Touro University California- Solano County Affiliated Clinics

    Fairfield, California, 94533

  • Seven Corners Medical Research Center

    Falls Church, Virginia, 22044

  • Parkway Medical Group

    Fayetteville, Tennessee, 37334

  • Feasterville Family Healthcare Center

    Feasterville, Pennsylvania, 19053

  • Quantum Research LLC

    Festus, Missouri, 63028

  • Family Health at Mount Olive

    Flanders, New Jersey, 07836

  • Flint Clinical Research

    Flint, Michigan, 48503

  • Apex Medical Research MI, Inc.

    Flint, Michigan, 48504

  • NYHQ

    Flushing, New York, 11355

  • Colorado Health Medical Group Heart Center of the Rockies

    Fort Collins, Colorado, 80528

  • Medical Center of the Rockies Research

    Fort Collins, Colorado, 80528

  • Invesclinic

    Fort Lauderdale, Florida, 33308

  • Primary Care Associates

    Fort Myers, Florida, 33907

  • Lee Physician Group

    Fort Myers, Florida, 33908

  • Appalachian Research Associates

    Fort Payne, Alabama, 35967

  • The Medical Group of Texas

    Fort Worth, Texas, 76104

  • Texas Health Physicians Group

    Fort Worth, Texas, 76107

  • University Of California San Francisco

    Fresno, California, 93701

  • VACCHCS

    Fresno, California, 93703

  • The Cardiac and Vascular Institute

    Gainesville, Florida, 32605

  • University of Florida

    Gainesville, Florida, 32610

  • Garden City Hospital

    Garden City, Michigan, 48135

  • Stern Cardiovascular Foundation, Inc.

    Germantown, Tennessee, 38138

  • Christiana Care Health System

    Glen Mills, Pennsylvania, 19342

  • Genesys Regional Medical Center

    Grand Blanc, Michigan, 48439

  • Altru Health System Rehab Center

    Grand Forks, North Dakota, 58201

  • Great Falls Clinic Clinical Research Deptartment

    Great Falls, Montana, 59420

  • Cardiology Associates of Bellin Health

    Green Bay, Wisconsin, 54115

  • Eastern Cardiology

    Greenville, North Carolina, 27834

  • Gulfside Clinical Research, LLC

    Gulfport, Mississippi, 39501

  • Avant Research Associates, LLC

    Guntersville, Alabama, 35976

  • T&R Clinic, P.A.

    Haltom City, Texas, 76117

  • North Oaks Cardiology

    Hammond, Louisiana, 70403

  • Hampton Family Practice Research

    Hampton, Virginia, 23666

  • Tidewater Physicians Multispecialty Group

    Hampton, Virginia, 23666

  • National Clinical LLC

    Hamtramck, Michigan, 48212

  • Pinnacle Health Cardiovascular Institute

    Harrisburg, Pennsylvania, 17110

  • Pentucket Medical Associates, Inc.

    Haverhill, Massachusetts, 01830

  • Qway Research

    Hialeah, Florida, 33010

  • State of the Art Research

    Hialeah, Florida, 33010

  • Healing Touch C&C Research

    Hialeah, Florida, 33012

  • Luzmed Clinical Research Institute

    Hialeah, Florida, 33012

  • Viviana Perez MD Research & Cosmetics

    Hialeah, Florida, 33012

  • Elite Cardiac Research Center LLC

    Hialeah, Florida, 33013

  • Nova Clinical Research Clinic

    Hialeah, Florida, 33013

  • Best Quality Research, Inc.

    Hialeah, Florida, 33016

  • Cardiocare

    Hillsborough, New Jersey, 08844

  • South Florida Research Solutions, LLC

    Hollywood, Florida, 33021

  • John Gutleber Medical Research Office

    Homestead, Florida, 33030

  • VA Pacific Islands Health Care System

    Honolulu, Hawaii, 96819

  • Michele P. Sartori, MD

    Houston, Texas, 77030

  • Saadat Ansari MD LLC

    Huntsville, Alabama, 35801

  • Clinical Research Prime

    Idaho Falls, Idaho, 83404

  • Midwest Cardiology Associates

    Independence, Missouri, 64057

  • Krannert Institute Of Cardiology

    Indianapolis, Indiana, 46202

  • Community Hospital South

    Indianapolis, Indiana, 46227

  • Indiana Heart Physicians

    Indianapolis, Indiana, 46237

  • Miller - SC Internal Medicine Associates.: Irmo

    Irmo, South Carolina, 29063

  • University of MS Medical Center

    Jackson, Mississippi, 39216

  • Kore Cardiovascular Research Institutue

    Jackson, Tennessee, 38305

  • Jamaica Hospital Medical Center

    Jamaica, New York, 11418

  • Freeman Health System

    Joplin, Missouri, 64804

  • Cardiovascular Medical Associates of Palm Beach

    Jupiter, Florida, 33458

  • VA Medical Center Kansas City

    Kansas City, Missouri, 64128

  • Grand Medical Care

    Katy, Texas, 77494

  • Team Research Of Central Texas

    Killeen, Texas, 76543

  • Houston Heart and Vascular Associates

    Kingwood, Texas, 77339

  • Hope Clinical Research

    Kissimmee, Florida, 34758

  • SIH Research, LLC

    Kissimmee, Florida, 34759

  • New Phase Research & Development

    Knoxville, Tennessee, 37909

  • Cardiovascular Research of Knoxville

    Knoxville, Tennessee, 37917

  • UCSD Sulpizio Cardiovascular Center

    La Jolla, California, 92037

  • University Of California San Diego

    La Jolla, California, 92093

  • Desert Medical Care & Wellness

    La Quinta, California, 92253

  • Barrett Clinic, P.C.

    La Vista, Nebraska, 68128

  • Kumar Medical Corporation

    Lancaster, California, 93534

  • Colonnade Medical Group

    Lancaster, Ohio, 43130

  • George Isajiw, MD

    Lansdowne, Pennsylvania, 19050

  • Internal Medicine Clinic

    Las Vegas, Nevada, 89102

  • Red Rock Clinical Research, LLC

    Las Vegas, Nevada, 89146

  • Utah Cardiology, P.C.

    Layton, Utah, 84041

  • VA Central Western Massachusetts Healthca

    Leeds, Massachusetts, 01053

  • Northside Clinical Research

    Lenoir, North Carolina, 28645

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Ocean State Clinical Research Prtnr

    Lincoln, Rhode Island, 02865

  • New Jersey Heart

    Linden, New Jersey, 07063

  • Unity Clinical Research

    Lindsay, Oklahoma, 73052

  • Arkansas Cardiology

    Little Rock, Arkansas, 72205

  • Arkansas Heart Hospital

    Little Rock, Arkansas, 72211

  • Loma Linda University Health

    Loma Linda, California, 92354

  • VA Loma Linda Healthcare System

    Loma Linda, California, 92357

  • Long Beach Center for Clinical Research

    Long Beach, California, 90807

  • Cardiovascular Innovation and Research

    Long Beach, California, 90813

  • Los Alamitos Cardiovascular

    Los Alamitos, California, 90720

  • Faye Montegrande Md. Clinical Research

    Los Angeles, California, 90004

  • Eastside Clinical Research Associates

    Los Angeles, California, 90022

  • Salman Khan A. Medical Corporation

    Los Angeles, California, 90033

  • University of Southern California

    Los Angeles, California, 90033

  • West LA VA Medical Center

    Los Angeles, California, 90049

  • Robley Rex VAMC

    Louisville, Kentucky, 40202

  • Stoddard - University of Louisville

    Louisville, Kentucky, 40202

  • Bays - L-MARC Research Center

    Louisville, Kentucky, 40213

  • Dean Foundation

    Madison, Wisconsin, 53715

  • University Of Wisconsin

    Madison, Wisconsin, 53715

  • Virginia Cardiovascular Associates

    Manassas, Virginia, 20109

  • Manassas Clinical Research Center

    Manassas, Virginia, 20110

  • American Clinical Research, LLC

    Marrero, Louisiana, 70072

  • Grace Research, LLC

    Marshall, Texas, 75670

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • VA Northern California Health Care

    Mather, California, 95655

  • Valley Heart Consultants

    McAllen, Texas, 78503

  • Tucker Cardiology Associates, P.C.

    Mechanicsville, Virginia, 23116

  • Southern Oregon Cardiology, LLC

    Medford, Oregon, 97504

  • Ramanathan - VAMC Memphis

    Memphis, Tennessee, 38104

  • CardioVascular Associates of Mesa

    Mesa, Arizona, 85206

  • Medical Research Center of Florida

    Miami, Florida, 33122

  • LG Diagnostics, Inc.

    Miami, Florida, 33126

  • St. Paul Medical Research Center, Inc.

    Miami, Florida, 33126

  • Team Medical Research

    Miami, Florida, 33134

  • Paradise Clinical Research, LLC

    Miami, Florida, 33144

  • GAD Research Center

    Miami, Florida, 33155

  • Innovation Research Institute, Inc.

    Miami, Florida, 33155

  • Sanitas Research

    Miami, Florida, 33155

  • Segui - Med Care Research

    Miami, Florida, 33165

  • South Florida Research Group, LLC

    Miami, Florida, 33176

  • Vista Health Research, LLC

    Miami, Florida, 33176

  • D De La Vega MD Research Group

    Miami, Florida, 33186

  • Lakes Research, LLC

    Miami Lakes, Florida, 33014

  • Veritas Research Corp.

    Miami Lakes, Florida, 33014

  • Ocean Blue Medical Research Center

    Miami Springs, Florida, 33166

  • Middletown Cardiovascular Associates

    Middletown, Ohio, 45044

  • South Shore Internal Medicine

    Milton, Massachusetts, 02186

  • Columbia St. Mary's

    Milwaukee, Wisconsin, 53211

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Long Island Heart Associates

    Mineola, New York, 11501

  • Winthrop University Hospital

    Mineola, New York, 11501

  • Heart Center, Palo Pinto General Hospital

    Mineral Wells, Texas, 76067

  • Valley Central Research Inc

    Mission, Texas, 78572

  • Cone - Montana Medical Research

    Missoula, Montana, 59801

  • University of South Alabama: Division of Clinical Research

    Mobile, Alabama, 36617

  • Lake Shore Clinical Research, LLC.

    Mooresville, North Carolina, 28117

  • Carteret Medical Group

    Morehead City, North Carolina, 28557

  • Cardiology Associates of Carolinas, PA

    Morganton, North Carolina, 28655

  • Bucks County Clinical Research

    Morrisville, Pennsylvania, 19067

  • Medical Consultants, PC

    Muncie, Indiana, 47303

  • Southwest Florida Research, LLC

    Naples, Florida, 34102

  • Lahey Cardiology

    Nashua, New Hampshire, 03060

  • Clinical Research Center Meharry Medical College

    Nashville, Tennessee, 37208

  • Otis Barnum D.O.P.C.

    Natchitoches, Louisiana, 71457

  • Jersey Shore University Medical Center

    Neptune City, New Jersey, 07753

  • Eastern Nephrology Associates, PLLC

    New Bern, North Carolina, 28562

  • Cardiovascular Institute

    New Brunswick, New Jersey, 08901

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • Queens Long Island Medical Group

    New Hyde Park, New York, 11577

  • Tulane University Office of Health Research

    New Orleans, Louisiana, 70112

  • Chinatown Cardiology, PC

    New York, New York, 10013

  • Weill Cornell Medical College and NY Presbyterian

    New York, New York, 10021

  • Mount Sinai School of Medicine

    New York, New York, 10029

  • Cardiology Physicians/Red Clay Research

    Newark, Delaware, 19713

  • TPMG Clinical Research

    Newport News, Virginia, 23606

  • Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • Illinois Heart & Lung Research Center, SC

    Normal, Illinois, 61761

  • Palisade Medical Center

    North Bergen, New Jersey, 07047

  • Captain James A. Lovell Federal Health

    North Chicago, Illinois, 60064

  • DiGiovanna Institute for Medical Education and Research

    North Massapequa, New York, 11758

  • North Hills Medical Research, Inc

    North Richland Hills, Texas, 76180

  • Valley Clinical Trials, Inc.

    Northridge, California, 91325

  • COR Clinical Research, LLC

    Oklahoma City, Oklahoma, 73103

  • Thadani - VA Medical Center Oklahoma City, OK

    Oklahoma City, Oklahoma, 73104

  • Today Clinical Research

    Oklahoma City, Oklahoma, 73129

  • Cardiovascular Health Clinic

    Oklahoma City, Oklahoma, 73134

  • Charlotte Hearts

    Old Point Station, South Carolina, 29707

  • Specialty Physicians of Illinois, LLC

    Olympia Fields, Illinois, 60461

  • Heart Consultants

    Omaha, Nebraska, 68114

  • Alegent Creighton Health

    Omaha, Nebraska, 68131

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Orange County Heart Institute & Research

    Orange, California, 92868

  • University of CA Irvine Medical Center

    Orange, California, 92868

  • Orlando Healthy Heart Institute

    Orlando, Florida, 32806

  • Lake Regional Cardiovascular Institute

    Osage Beach, Missouri, 65065

  • Stahl - Midwest Heart & Vascular Specialists

    Overland Park, Kansas, 66209

  • Research Integrity LLC

    Owensboro, Kentucky, 42303

  • Diverse Research Solutions

    Oxnard, California, 93030

  • Grace Research, LLC

    Palestine, Texas, 75801

  • Palm Beach Gardens Research Center, LLC

    Palm Beach Gardens, Florida, 33410

  • Unrein - Rocky Vista University Health Center

    Parker, Colorado, 80134

  • Huntington Memorial Hospital

    Pasadena, California, 91105

  • Inlet Cardiopulmonary & Associates

    Pawleys Island, South Carolina, 29585

  • Memorial Hospital of Rhode Island

    Pawtucket, Rhode Island, 02860

  • Lahey Medical Center

    Peabody, Massachusetts, 02149

  • Broward Research Center

    Pembroke Pines, Florida, 33024

  • Pioneer Clinical Research

    Pembroke Pines, Florida, 33024

  • Sandoval - Broward Research Center

    Pembroke Pines, Florida, 33204

  • Drexel University College of Medicine

    Philadelphia, Pennsylvania, 19102

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Arizona Arthritis & Rheumatology Research

    Phoenix, Arizona, 85032

  • Champlain Valley Physician Hospital

    Plattsburgh, New York, 12901

  • Avant Research Associates, LLC

    Port Arthur, Texas, 77640

Other trials in United States

Canada60 sites

  • Bramalea Medical Centre

    Brampton, Ontario, L6T 4S5

  • Brampton Research Associates

    Brampton, Ontario, L6Z 4N5

  • Viacar Recherche Clinique Inc.

    Brossard, Quebec, J4X1S4

  • Philippe R Beaudry Medicine Professional Corporation

    Burlington, Ontario, L7R 4E2

  • Vizel Cardiac Research

    Cambridge, Ontario, N1R7R1

  • Dr. Linda Sinnaeve's Office

    Chatham, Ontario, N7L 1C1

  • Ecogene-21

    Chicoutimi, Quebec, G7H 7K9

  • Q&T Research Chicoutimi

    Chicoutimi, Quebec, G7H 7Y8

  • Scisco Clinical Research

    Cornwall, Ontario, K6H 4M4

  • G.S. Cardiac Lab Medicine Professional Corp

    Greater Sudbury, Ontario, P3C 1S8

  • Dr. R. Labonte Professional Med Corp

    Greater Sudbury, Ontario, P3E 3B8

  • Dr. G. Garrioch, Independent Practice

    Greater Sudbury, Ontario, P3E 3C6

  • Viacar Recherche Clinique Inc.

    Greenfield Park, Quebec, J4V2G8

  • Dr. Peter Spadafora Health Center

    Guelph, Ontario, N1E 5G6

  • John Stimac, MD

    Hamilton, Ontario, L8L 5G4

  • KMH Cardiology & Diagnostics: Hamilton

    Hamilton, Ontario, L8P 3A9

  • Dr. William Liang

    Hamilton, Ontario, L8W3J6

  • Source Unique Clinic

    Hawkesbury, Ontario, K6A 1A1

  • Dr. Ronald Fowlis

    Kitchener, Ontario, N2M 5NG

  • University Hospital

    London, Ontario, N6A 5A5

  • Malton Medical Research

    Mississauga, Ontario, L4T 4J2

  • KMH Cardiology & Diagnostics: Mississauga

    Mississauga, Ontario, L5K 2L3

  • Sewa Ram Singal Medicine Professional Corporation

    Mississauga, Ontario, L5U 0A6

  • CHUM Hotel-Dieu

    Montreal, Quebec, H2W 1T8

  • Newmarket Cardiology Research Group

    Newmarket, Ontario, l3y -8c3

  • Newmarket Cardiology Research Group

    Newmarket, Ontario, L3Y 8C3

  • Portage Medical Centre

    Niagara Falls, Ontario, I2E6A6

  • The Medical Arts Health Research Group

    North Vancouver, British Columbia, V7M 2H4

  • Humber River Regional Hospital

    North York, Ontario, M3N2V6

  • Bakbak Medicine Professional Corporation

    Oshawa, Ontario, L1H 1B9

  • Dr. James Y. Cha

    Oshawa, Ontario, L1J2K1

  • University Of Ottawa Heart Institute

    Ottawa, Ontario, k1y -4w7

  • The Medical Arts Health Research Group

    Penticton, British Columbia, V2A 5C8

  • Kawartha Cardiology Clinical Trials

    Peterborough, Ontario, K9J0B2

  • Steeple Hill Medical Centre

    Pickering, Ontario, L1V 2A6

  • Recherche Clinique Sigma, Inc.

    Québec, Quebec, G1G3Z4

  • Iucpq

    Québec, Quebec, G1V 4G5

  • ALPHA Recherche Clinique

    Québec, Quebec, G3K 2P8

  • CardioVasc HR

    Saint-Jean-sur-Richelieu, Quebec, j3a-1c3

  • ViaCar Recherche Clinique Inc

    Saint-Lambert, Quebec, J4P 2H4

  • Viacar Recherche Clinique

    Saint-Lambert, Quebec, J4P 2J2

  • Sarnia Institute Of Clinical Research

    Sarnia, Ontario, N7T 4X3

  • Scarborough Cardiology Research

    Scarborough Village, Ontario, M1E5E9

  • Scarborough General Hospital Cardiology Research Associates

    Scarborough Village, Ontario, M1PT27

  • Milliken Medical Centre

    Scarborough Village, Ontario, M1V5P6

  • Canadian Centre for Research on Diabetes

    Smith Falls, Ontario, K7A 4W8

  • Lake Shore Cardiology

    St. Catharines, Ontario, L2S 2Y3

  • Sardar Medical Clinic

    St. Thomas, Ontario, N5R 2R4

  • Hopital Pierre-Le Gardeur

    Terrebonne, Quebec, J6V 2H2

  • Dr. Laurence Gibbs Medicine Professional Corp.

    Thedford, Ontario, N0M 2N0

  • Tillsonburg Medical Centre

    Tillsonburg, Ontario, N4G 5A7

  • Humber River Hospital

    Toronto, Ontario, M3M 0B2

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • Toronto General Hospital

    Toronto, Ontario, M5G 2N2

  • Weston Road Medical Clinic

    Toronto, Ontario, M9N 2A7

  • Dr. Nigel Jagan Medicine Professional Corporation

    Whitby, Ontario, L1N 2L1

  • Dr. Nwadiaro Medicine Professional Corp

    Windsor, Ontario, N8X 1L9

  • Winnipeg Clinic

    Winnipeg, Manitoba, R3C 0N2

Other trials in Canada

Puerto Rico6 sites

  • Instituto Sanacoop

    Bayamón, 00961

  • San Juan Bautista School of Medicine

    Caguas, 00727

  • Norma S. Severino-Pacheco, MD

    Canovanas, 00729

  • Cardiometabolic Research Center

    Ponce, 00717

  • Miguel Sosa-Padilla, MD

    San Juan, 00926-2832

  • Yolanda Sierra Quinones, MD

    Toa Baja, 00949

Other trials in Puerto Rico

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Event-driven Trial of Weekly Low-dose Methotrexate (LDM) in the Prevention of Cardiovascular Events Among Stable Coronary Artery Disease Patients With Type 2 Diabetes or Metabolic Syndrome

The Cardiovascular Inflammation Reduction Trial (CIRT) is a randomized clinical trial investigating whether taking low-dose methotrexate reduces heart attacks, strokes, or death in people with type 2 diabetes or metabolic syndrome that have had a heart attack or multiple coronary blockages. This trial is funded by the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH).

Read the detailed description

While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have either suffered documented myocardial infarction in the past or have angiographically demonstrated multivessel coronary artery disease in the past will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.

Being tested
Methotrexate, Placebo
Keywords
Myocardial Infarction, Stroke, Cardiovascular death, Type 2 Diabetes, Metabolic Syndrome, Cardiovascular Inflammation, Atherothrombosis
Medical subject headings
Cardiovascular Diseases, Myocardial Infarction, Stroke, Diabetes Mellitus, Type 2, Metabolic Syndrome, Thrombosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethotrexateDrug

    Also called Trexall, TEVA Inc (brand of methotrexate)

    Tablet, Oral, Target dose 15-20 mg weekly plus 1.0 mg folic acid 6 days/week

  • PlaceboDrug

    Tablet, Oral, weekly plus 1.0 mg folic acid 6 days/week

Study groups in NCT01594333
Study groupRoleWhat they receive
MethotrexateExperimentalMethotrexate: Tablet, Oral, Target dose 15-20mg weekly plus 1.0 mg folic acid 6 days/week
Receives: Drug: Methotrexate
PlaceboPlacebo comparatorPlacebo: Tablet, Oral weekly plus 1.0mg folic acid 6 days/week
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Subjects With Major Adverse Cardiovascular Events

    The first occurrence of Major Adverse Cardiovascular Event which is defined as the occurrence of one or more of the following: Cardiovascular Death, Non-Fatal Myocardial Infarction or Non-Fatal Stroke.

    Measured: From randomization to trial end (April 2, 2018) up to a maximum of 5 years

  2. Number of Subjects With Major Adverse Cardiovascular Event or Hospitalization for Unstable Angina That Led to Urgent Coronary Revascularization

    The first occurrence of Major Adverse Cardiovascular Event or Hospitalization for Unstable Angina that led to Urgent Coronary Revascularization.

    Measured: From randomization to trial end (April 2, 2018) - up to a maximum of 5 years

Secondary outcomes (5)

  1. Number of Subjects With All-cause Mortality

    Subjects who died from any cause.

    Measured: From randomization to the trial end (April 2, 2018) up to a maximum of 5 years

  2. Number of Subjects With Major Adverse Cardiovascular Event or Any Coronary Revascularization

    The first occurrence of Major Adverse Cardiovascular Event or Any Coronary Revascularization.

    Measured: From randomization to the trial end (April 2, 2018) - up to a maximum of 5 years

  3. Number of Subjects With Hospitalization for Congestive Heart Failure

    The first occurrence of Hospitalization for Congestive Heart Failure

    Measured: From randomization to trial end (April 2, 2018) up to a maximum of 5 years

  4. Number of Subjects With Major Adverse Cardiovascular Event, Coronary Revascularization, Hospitalization for Congestive Heart Failure or All Cause Mortality

    The first occurrence of Major Adverse Cardiovascular Event, Coronary Revascularization, Hospitalization for Congestive Heart Failure or All Cause Mortality.

    Measured: From randomization to trial end (April 2, 2018) up to a maximum of 5 years

  5. Number of Subjects With New Onset Type 2 Diabetes

    New onset type 2 diabetes among those without diabetes at baseline. Baseline diabetes is defined as any of the following prior to randomization: clinician report of diabetes, use of antidiabetic medication, hbA1c >=6.5 or fasting plasma glucose >=126.

    Measured: From randomization to the trial end (April 2, 2018) - up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 May 2012 (estimated)
  2. Study startApr 2013
  3. Primary completion15 Apr 2019
  4. Study completion30 Oct 2019

Resources

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
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
4,786 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01594333
Sponsor's protocol ID
2012P-000857
Other IDs
U01HL101422, U01HL101389
Acronym
CIRT
Status last verified
Jul 2020
First submitted
1 May 2012
Last updated
24 Jul 2020
Data monitoring committee
Yes

Publications

  • Cui J, Ridker PM, Solomon DH. Blood pressure changes during methotrexate treatment: results from a randomized placebo-controlled trial among patients with cardiovascular risk. Rheumatology (Oxford). 2025 Jun 1;64(6):3917-3920. doi: 10.1093/rheumatology/keae604.

    PubMed 39657237

  • Cui J, Di Martino V, Solomon DH. Longitudinal Follow-Up of Fibrosis-4 in Patients at Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease Receiving Low-Dose Methotrexate Treatment. Clin Gastroenterol Hepatol. 2024 Nov;22(11):2337-2339. doi: 10.1016/j.cgh.2024.03.035. Epub 2024 Apr 24.

    PubMed 38663834

  • Cui J, Chasman DI, Raychaudhuri S, Xu C, Ridker PM, Solomon DH, Karlson EW. Genetics are not likely to offer clinically useful predictions for elevated liver enzyme levels in patients using low dose methotrexate. Semin Arthritis Rheum. 2022 Aug;55:152036. doi: 10.1016/j.semarthrit.2022.152036. Epub 2022 May 28.

    PubMed 35671649

  • Reiss AB, Teboul I, Kasselman L, Ahmed S, Carsons SE, De Leon J. Methotrexate effects on adenosine receptor expression in peripheral monocytes of persons with type 2 diabetes and cardiovascular disease. J Investig Med. 2022 Aug;70(6):1433-1437. doi: 10.1136/jim-2022-002355. Epub 2022 May 23.

    PubMed 35606100

  • Sparks JA, Vanni KMM, Sparks MA, Xu C, Santacroce LM, Glynn RJ, Ridker PM, Solomon DH. Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial. J Am Soc Nephrol. 2021 Dec 1;32(12):3197-3207. doi: 10.1681/ASN.2021050598. Epub 2021 Dec 1.

    PubMed 34551998

  • Xu C, Selhub J, Jacques P, Paynter NP, MacFadyen JG, Glynn RJ, Ridker PM, Solomon DH. Adverse effects related to methotrexate polyglutamate levels: adjudicated results from the cardiovascular inflammation reduction trial. Rheumatology (Oxford). 2021 Jun 18;60(6):2963-2968. doi: 10.1093/rheumatology/keaa650.

    PubMed 34144603

  • Sparks JA, Dellaripa PF, Glynn RJ, Paynter NP, Xu C, Ridker PM, Solomon DH. Pulmonary Adverse Events in Patients Receiving Low-Dose Methotrexate in the Randomized, Double-Blind, Placebo-Controlled Cardiovascular Inflammation Reduction Trial. Arthritis Rheumatol. 2020 Dec;72(12):2065-2071. doi: 10.1002/art.41452. Epub 2020 Oct 7.

    PubMed 32741143

  • Ridker PM, MacFadyen JG, Glynn RJ, Bradwin G, Hasan AA, Rifai N. Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial. Eur Heart J. 2020 Aug 14;41(31):2952-2961. doi: 10.1093/eurheartj/ehaa160.

    PubMed 32221587

  • Solomon DH, Glynn RJ, Karlson EW, Lu F, Corrigan C, Colls J, Xu C, MacFadyen J, Barbhaiya M, Berliner N, Dellaripa PF, Everett BM, Pradhan AD, Hammond SP, Murray M, Rao DA, Ritter SY, Rutherford A, Sparks JA, Stratton J, Suh DH, Tedeschi SK, Vanni KMM, Paynter NP, Ridker PM. Adverse Effects of Low-Dose Methotrexate: A Randomized Trial. Ann Intern Med. 2020 Mar 17;172(6):369-380. doi: 10.7326/M19-3369. Epub 2020 Feb 18.

    PubMed 32066146

  • Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, Mam V, Hasan A, Rosenberg Y, Iturriaga E, Gupta M, Tsigoulis M, Verma S, Clearfield M, Libby P, Goldhaber SZ, Seagle R, Ofori C, Saklayen M, Butman S, Singh N, Le May M, Bertrand O, Johnston J, Paynter NP, Glynn RJ; CIRT Investigators. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019 Feb 21;380(8):752-762. doi: 10.1056/NEJMoa1809798. Epub 2018 Nov 10.

    PubMed 30415610

  • Everett BM, Pradhan AD, Solomon DH, Paynter N, Macfadyen J, Zaharris E, Gupta M, Clearfield M, Libby P, Hasan AA, Glynn RJ, Ridker PM. Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis. Am Heart J. 2013 Aug;166(2):199-207.e15. doi: 10.1016/j.ahj.2013.03.018. Epub 2013 May 3.

    PubMed 23895801

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Methotrexate in people with Cardiovascular Disease, run by Brigham and Women's Hospital at 470 sites in 3 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 6 inclusion and 13 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 24 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 470 sites in United States, Canada, Puerto Rico. 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?

Yes. Results are posted in the registry (first posted 24 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Subjects With Major Adverse Cardiovascular Events (time frame: From randomization to trial end (April 2, 2018) up to a maximum of 5 years). 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 NCT01594333, which also lists 11 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 24 Jul 2020.

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