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Cardiovascular Inflammation Reduction Trial (CIRT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01594333
Recruitment Status : Active, not recruiting
First Posted : May 9, 2012
Last Update Posted : April 5, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Paul Ridker, Brigham and Women's Hospital

Brief 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. This trial is funded by the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH).

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Drug: Methotrexate Drug: Placebo Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 7000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Study Start Date : April 2013
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Methotrexate Drug: Methotrexate
Tablet, Oral, Target dose 15-20 mg weekly plus 1.0 mg folic acid 6 days/week
Other Name: Trexall, TEVA Inc (brand of methotrexate)
Placebo Comparator: Placebo Drug: Placebo
Tablet, Oral, weekly plus 1.0 mg folic acid 6 days/week



Primary Outcome Measures :
  1. Rate of major cardiovascular events [ Time Frame: Up to six years ]
    Investigate whether 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.


Secondary Outcome Measures :
  1. Rate of all-cause mortality [ Time Frame: Up to six years ]
  2. Rate of the primary endpoint plus coronary revascularization [ Time Frame: Up to six years ]
  3. Rate of hospitalization for congestive heart failure [ Time Frame: Up to six years ]
  4. Rate of primary endpoint plus all-cause mortality plus coronary revascularization plus congestive heart failure [ Time Frame: Up to six years ]
  5. Rate of new onset type 2 diabetes among those with metabolic syndrome but not diabetes at study entry [ Time Frame: Up to six years ]

Other Outcome Measures:
  1. Rate of the primary endpoint plus unstable angina requiring unplanned coronary revascularization [ Time Frame: Up to six years ]
  2. Rate of coronary revascularization [ Time Frame: Up to six years ]
  3. Rate of peripheral artery disease [ Time Frame: Up to six years ]
  4. Rate of symptomatic deep vein thrombosis or pulmonary embolism, including those considered to be provoked and those considered to be idiopathic [ Time Frame: Up to six years ]
  5. Rate of clinically significant aortic stenosis [ Time Frame: Up to six years ]
  6. Rate of atrial fibrillation [ Time Frame: Up to six years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 Cockroft-Gault equation;
  • History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01594333


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Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Appalachian Research Associates
Fort Payne, Alabama, United States, 35967
Avant Research Associates, LLC
Guntersville, Alabama, United States, 35976
Saadat Ansari MD LLC
Huntsville, Alabama, United States, 35801
University of South Alabama: Division of Clinical Research
Mobile, Alabama, United States, 36617
United States, Arizona
Heart Vascular of Northern Arizona
Cottonwood, Arizona, United States, 86326
CardioVascular Associates of Mesa
Mesa, Arizona, United States, 85206
Arizona Arthritis & Rheumatology Research
Phoenix, Arizona, United States, 85032
Scottsdale Medical Imaging
Scottsdale, Arizona, United States, 85258
The Heart Clinic
Scottsdale, Arizona, United States, 85258
Pima Heart
Tucson, Arizona, United States, 85718
Southern Arizona VA Health Care System
Tucson, Arizona, United States, 85723
United States, Arkansas
Arkansas Cardiology
Little Rock, Arkansas, United States, 72205
Arkansas Heart Hospital
Little Rock, Arkansas, United States, 72211
United States, California
Oracle Clinical Research, Inc.
Anaheim, California, United States, 92801
Medical Group of Culver City
Culver City, California, United States, 90230
Touro University California- Solano County Affiliated Clinics
Fairfield, California, United States, 94533
University Of California San Francisco
Fresno, California, United States, 93701
VACCHCS
Fresno, California, United States, 93703
UCSD Sulpizio Cardiovascular Center
La Jolla, California, United States, 92037
University Of California San Diego
La Jolla, California, United States, 92093
Desert Medical Care & Wellness
La Quinta, California, United States, 92253
Kumar Medical Corporation
Lancaster, California, United States, 93534
Loma Linda University Health
Loma Linda, California, United States, 92354
VA Loma Linda Healthcare System
Loma Linda, California, United States, 92357
Long Beach Center for Clinical Research
Long Beach, California, United States, 90807
Cardiovascular Innovation and Research
Long Beach, California, United States, 90813
Los Alamitos Cardiovascular
Los Alamitos, California, United States, 90720
Faye Montegrande Md. Clinical Research
Los Angeles, California, United States, 90004
Eastside Clinical Research Associates
Los Angeles, California, United States, 90022
Salman Khan A. Medical Corporation
Los Angeles, California, United States, 90033
University of Southern California
Los Angeles, California, United States, 90033
West LA VA Medical Center
Los Angeles, California, United States, 90049
VA Northern California Health Care
Mather, California, United States, 95655
Valley Clinical Trials, Inc.
Northridge, California, United States, 91325
Orange County Heart Institute & Research
Orange, California, United States, 92868
University of CA Irvine Medical Center
Orange, California, United States, 92868
Diverse Research Solutions
Oxnard, California, United States, 93030
Huntington Memorial Hospital
Pasadena, California, United States, 91105
Central Coast Cardiology
Salinas, California, United States, 93901
Richard G. Friedman, MD
San Diego, California, United States, 92103
Ritchken and First MDs
San Diego, California, United States, 92117
Foundation for Cardiovascular Medicine
San Diego, California, United States, 92121
San Diego Cardiac Center
San Diego, California, United States, 92123
Veterans Affairs San Diego Healthcare System
San Diego, California, United States, 92161
UCSF at Zuckerberg SF General Hospital
San Francisco, California, United States, 94110
Coastal Heart Medical Group, Inc.
Santa Ana, California, United States, 92704
Comprehensive Cardiovascular Care
Santa Maria, California, United States, 93454
Pacific Heart and Vascular Medical Group
Stockton, California, United States, 95210
Manoj D. Aswani M.D.
Thousand Oaks, California, United States, 91360
Touro University California- Solano Public Health Affiliated Clinics
Vallejo, California, United States, 94592
United States, Colorado
Munni R. Selagamsetty, Md, Pc
Colorado Springs, Colorado, United States, 80910
Vijay - Aurora Denver Cardiology
Denver, Colorado, United States, 80218
Colorado Health Medical Group Heart Center of the Rockies
Fort Collins, Colorado, United States, 80528
Medical Center of the Rockies Research
Fort Collins, Colorado, United States, 80528
Unrein - Rocky Vista University Health Center
Parker, Colorado, United States, 80134
United States, Connecticut
Connecticut Heart and Vascular Center
Bridgeport, Connecticut, United States, 06606
Bridgeport Hospital
Bridgeport, Connecticut, United States, 06610
United States, Delaware
Cardiology Physicians/Red Clay Research
Newark, Delaware, United States, 19713
United States, District of Columbia
Boisey Barnes MD, PC
Washington, District of Columbia, United States, 20024
GWU Medical Faculty Associatin, Inc.
Washington, District of Columbia, United States, 20037
United States, Florida
Pianko - Aventura Research Center, LLC
Aventura, Florida, United States, 33180
North Ridge Heart Associates
Boca Raton, Florida, United States, 33434
St. Francis Medical Institute
Clearwater, Florida, United States, 33765
Gonzalez MD & Aswad MD Health Ser
Coral Gables, Florida, United States, 33134
American Research Institute, Inc.
Cutler Bay, Florida, United States, 33157
Daytona Heart Group
Daytona Beach, Florida, United States, 32114
Daytona Heart Group
DeLand, Florida, United States, 32720
Seidman Clinical Trials
Delray Beach, Florida, United States, 33484
Steven Cohen MD
Delray Beach, Florida, United States, 33484
Infinite Clinical Research
Doral, Florida, United States, 33126
International Research Partners, LLC
Doral, Florida, United States, 33166
Medical Research Institute at Doral, Inc.
Doral, Florida, United States, 33178
Lake Internal Medicine Assocaties
Eustis, Florida, United States, 32726
Invesclinic
Fort Lauderdale, Florida, United States, 33308
Primary Care Associates
Fort Myers, Florida, United States, 33907
Lee Physician Group
Fort Myers, Florida, United States, 33908
The Cardiac and Vascular Institute
Gainesville, Florida, United States, 32605
University of Florida
Gainesville, Florida, United States, 32610
Qway Research
Hialeah, Florida, United States, 33010
State of the Art Research
Hialeah, Florida, United States, 33010
Healing Touch C&C Research
Hialeah, Florida, United States, 33012
Luzmed Clinical Research Institute
Hialeah, Florida, United States, 33012
Viviana Perez MD Research & Cosmetics
Hialeah, Florida, United States, 33012
Elite Cardiac Research Center LLC
Hialeah, Florida, United States, 33013
Nova Clinical Research Clinic
Hialeah, Florida, United States, 33013
Best Quality Research, Inc.
Hialeah, Florida, United States, 33016
South Florida Research Solutions, LLC
Hollywood, Florida, United States, 33021
John Gutleber Medical Research Office
Homestead, Florida, United States, 33030
Cardiovascular Medical Associates of Palm Beach
Jupiter, Florida, United States, 33458
Hope Clinical Research
Kissimmee, Florida, United States, 34758
SIH Research, LLC
Kissimmee, Florida, United States, 34759
Lakes Research, LLC
Miami Lakes, Florida, United States, 33014
Veritas Research Corp.
Miami Lakes, Florida, United States, 33014
Ocean Blue Medical Research Center
Miami Springs, Florida, United States, 33166
Medical Research Center of Florida
Miami, Florida, United States, 33122
LG Diagnostics, Inc.
Miami, Florida, United States, 33126
St. Paul Medical Research Center, Inc.
Miami, Florida, United States, 33126
Team Medical Research
Miami, Florida, United States, 33134
Paradise Clinical Research, LLC
Miami, Florida, United States, 33144
GAD Research Center
Miami, Florida, United States, 33155
Innovation Research Institute, Inc.
Miami, Florida, United States, 33155
Sanitas Research
Miami, Florida, United States, 33155
Segui - Med Care Research
Miami, Florida, United States, 33165
South Florida Research Group, LLC
Miami, Florida, United States, 33176
Vista Health Research, LLC
Miami, Florida, United States, 33176
D De La Vega MD Research Group
Miami, Florida, United States, 33186
Southwest Florida Research, LLC
Naples, Florida, United States, 34102
Orlando Healthy Heart Institute
Orlando, Florida, United States, 32806
Palm Beach Gardens Research Center, LLC
Palm Beach Gardens, Florida, United States, 33410
Broward Research Center
Pembroke Pines, Florida, United States, 33024
Pioneer Clinical Research
Pembroke Pines, Florida, United States, 33024
Sandoval - Broward Research Center
Pembroke Pines, Florida, United States, 33204
Bay Area Heart Center: 49th Street
Saint Petersburg, Florida, United States, 33705
Bay Area Heart Center: 7th Avenue
Saint Petersburg, Florida, United States, 33705
Lenus Research & Medical Group
Sweetwater, Florida, United States, 33172
DBC Research
Tamarac, Florida, United States, 33321
Asclepes Research Centers
Weeki Wachee, Florida, United States, 34607
Gupta - Premier Heart and Vascular Center
Wesley Chapel, Florida, United States, 33544
United States, Georgia
Athens Regional Medical Center
Athens, Georgia, United States, 30606
Atlanta Veterans Affairs Medical Center
Atlanta, Georgia, United States, 30033
Laureate Medical Group at Northside
Atlanta, Georgia, United States, 30308
Synergy Therapeutic Partners
Atlanta, Georgia, United States, 30308
Northside Hospital
Atlanta, Georgia, United States, 30342
Atlanta Heart Specialists, LLC
Cumming, Georgia, United States, 30041
Heart and Rhythm Specialists
Dalton, Georgia, United States, 30720
Albert F. Johary MD, PC
Dunwoody, Georgia, United States, 30338
Infinite Clinical Trials
Riverdale, Georgia, United States, 30274
Atlanta Vanguard Medical Associates
Smyrna, Georgia, United States, 30082
Herman Clinical Research, LLC
Suwanee, Georgia, United States, 30024
Atlanta Heart Specialists, LLC
Tucker, Georgia, United States, 30084
Cardiology Associates of Vidalia, P.C.
Vidalia, Georgia, United States, 30474
United States, Hawaii
VA Pacific Islands Health Care System
Honolulu, Hawaii, United States, 96819
United States, Idaho
St. Luke's Idaho Cardiology Associates
Boise, Idaho, United States, 83712
Clinical Research Prime
Idaho Falls, Idaho, United States, 83404
United States, Illinois
Northwest Heart Clinical Research
Arlington Heights, Illinois, United States, 60005
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Advocate Med Group-Heart & Vascular Of Illinois
Chicago, Illinois, United States, 60657
Illinois Heart & Lung Research Center, SC
Normal, Illinois, United States, 61761
Captain James A. Lovell Federal Health
North Chicago, Illinois, United States, 60064
Specialty Physicians of Illinois, LLC
Olympia Fields, Illinois, United States, 60461
Advanced CardioVascular Consultants
Rock Island, Illinois, United States, 61201
United States, Indiana
Cardiospecialists, LTD
Dyer, Indiana, United States, 46311
Martin - Martin Family Practice and Research
Evansville, Indiana, United States, 47714
Krannert Institute Of Cardiology
Indianapolis, Indiana, United States, 46202
Community Hospital South
Indianapolis, Indiana, United States, 46227
Indiana Heart Physicians
Indianapolis, Indiana, United States, 46237
Medical Consultants, PC
Muncie, Indiana, United States, 47303
United States, Iowa
Iowa Heart Center
West Des Moines, Iowa, United States, 50266
United States, Kansas
Stahl - Midwest Heart & Vascular Specialists
Overland Park, Kansas, United States, 66209
Professional Research Network of KS
Wichita, Kansas, United States, 67203
Robert J. Dole VAMC
Wichita, Kansas, United States, 67230
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Robley Rex VAMC
Louisville, Kentucky, United States, 40202
Stoddard - University of Louisville
Louisville, Kentucky, United States, 40202
Bays - L-MARC Research Center
Louisville, Kentucky, United States, 40213
Research Integrity LLC
Owensboro, Kentucky, United States, 42303
United States, Louisiana
Dorothy H. Banish, MD, APMC Study Group
Covington, Louisiana, United States, 70433
Avant Research Associates, LLC
Crowley, Louisiana, United States, 70526
North Oaks Cardiology
Hammond, Louisiana, United States, 70403
American Clinical Research, LLC
Marrero, Louisiana, United States, 70072
Otis Barnum D.O.P.C.
Natchitoches, Louisiana, United States, 71457
Tulane University Office of Health Research
New Orleans, Louisiana, United States, 70112
Veterans Affairs Medical Center Shreveport
Shreveport, Louisiana, United States, 71101
United States, Maine
Maine Research Associates
Auburn, Maine, United States, 04210
Paul A. Shapero, M.D.
Bangor, Maine, United States, 04401
Southern Maine Health Care
Biddeford, Maine, United States, 04005
InterMed, PA
Portland, Maine, United States, 04101
Maine Medical Partners Maine Health Cardiology
South Portland, Maine, United States, 04106
Maine Centers for Healthcare
Westbrook, Maine, United States, 04092
United States, Maryland
Sinai Center for Thrombosis Research
Baltimore, Maryland, United States, 21215
St. Mary's Medical Center
Charlotte Hall, Maryland, United States, 20622
Calvert Memorial Hospital
Clinton, Maryland, United States, 20735
Shah Associates, MD, LLC
Prince Frederick, Maryland, United States, 20678
Peninsula Cardiology Associates
Salisbury, Maryland, United States, 21804
IRC Clinics
Towson, Maryland, United States, 21204
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
St. Elizabeth's Medical Center
Boston, Massachusetts, United States, 02135
MGH Cardiology
Boston, Massachusetts, United States, 02214
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
Lahey Hospital and Medical Center
Burlington, Massachusetts, United States, 01805
Massachusetts General Hospital - Chelsea Health Care Center
Chelsea, Massachusetts, United States, 02150
Pentucket Medical Associates, Inc.
Haverhill, Massachusetts, United States, 01830
VA Central Western Massachusetts Healthca
Leeds, Massachusetts, United States, 01053
South Shore Internal Medicine
Milton, Massachusetts, United States, 02186
Lahey Medical Center
Peabody, Massachusetts, United States, 02149
North Shore Cardiovascular Associates
Salem, Massachusetts, United States, 01907
Reliant Medical Group
Worcester, Massachusetts, United States, 01608
United States, Michigan
Endeavor Medical Research
Alpena, Michigan, United States, 49707
John D. Dingell Veterans Affairs Medical Center
Detroit, Michigan, United States, 48201
Trace Research Group at Wayne State University
Detroit, Michigan, United States, 48201
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Flint Clinical Research
Flint, Michigan, United States, 48503
Apex Medical Research MI, Inc.
Flint, Michigan, United States, 48504
Garden City Hospital
Garden City, Michigan, United States, 48135
Genesys Regional Medical Center
Grand Blanc, Michigan, United States, 48439
National Clinical LLC
Hamtramck, Michigan, United States, 48212
Academic Cardiology Associates PC
Rochester Hills, Michigan, United States, 48307
Beaumont Health Center
Royal Oak, Michigan, United States, 48073
Covenant Medical Center, Inc.
Saginaw, Michigan, United States, 48602
Mid-Michigan Heart & Vascular Center
Saginaw, Michigan, United States, 48609
United States, Minnesota
Centra Care Heart & Vascular Center at St. Cloud Hospital
Saint Cloud, Minnesota, United States, 56303
United Heart and Vascular Clinic
Saint Paul, Minnesota, United States, 55102
United States, Mississippi
Gulfside Clinical Research, LLC
Gulfport, Mississippi, United States, 39501
University of MS Medical Center
Jackson, Mississippi, United States, 39216
David M. Headley M.D. PA Planters Clinic
Port Gibson, Mississippi, United States, 39150
Stern Cardiovascular Foundation, Inc.
Southaven, Mississippi, United States, 38671
United States, Missouri
Center for Advanced Medicine and Research LLC
Bridgeton, Missouri, United States, 63044
Clinical Research Center University of Missouri
Columbia, Missouri, United States, 65212
Quantum Research LLC
Festus, Missouri, United States, 63028
Midwest Cardiology Associates
Independence, Missouri, United States, 64057
Freeman Health System
Joplin, Missouri, United States, 64804
VA Medical Center Kansas City
Kansas City, Missouri, United States, 64128
Lake Regional Cardiovascular Institute
Osage Beach, Missouri, United States, 65065
VA St. Louis Health Care System (VASTLHCS)
Saint Louis, Missouri, United States, 63106
SLUCare Cardiology
Saint Louis, Missouri, United States, 63110
Washington University
Saint Louis, Missouri, United States, 63110
Clinical Investigators LLC
Saint Louis, Missouri, United States, 63119
Consult and Research Associates
Saint Louis, Missouri, United States, 63122
Center for Advanced Medicine and Research
Saint Peters, Missouri, United States, 63303
CoxHealth: Wheeler Heart & Vascular Center
Springfield, Missouri, United States, 65807
Mercy Medical Research Institute
Springfield, Missouri, United States, 65807
United States, Montana
Great Falls Clinic Clinical Research Deptartment
Great Falls, Montana, United States, 59420
Cone - Montana Medical Research
Missoula, Montana, United States, 59801
United States, Nebraska
Barrett Clinic, P.C.
La Vista, Nebraska, United States, 68128
Heart Consultants
Omaha, Nebraska, United States, 68114
Alegent Creighton Health
Omaha, Nebraska, United States, 68131
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Nevada
Internal Medicine Clinic
Las Vegas, Nevada, United States, 89102
Red Rock Clinical Research, LLC
Las Vegas, Nevada, United States, 89146
Sierra Nevada Health Care System
Reno, Nevada, United States, 89502
Renown Inst for Heart & Vasc Health
Reno, Nevada, United States, 89503
United States, New Hampshire
Lahey Cardiology
Nashua, New Hampshire, United States, 03060
United States, New Jersey
Family Health at Mount Olive
Flanders, New Jersey, United States, 07836
Cardiocare
Hillsborough, New Jersey, United States, 08844
New Jersey Heart
Linden, New Jersey, United States, 07063
Jersey Shore University Medical Center
Neptune, New Jersey, United States, 07753
Cardiovascular Institute
New Brunswick, New Jersey, United States, 08901
Palisade Medical Center
North Bergen, New Jersey, United States, 07047
The Valley Hospital
Ridgewood, New Jersey, United States, 07450
Mercer Bucks Cardiology
Robbinsville, New Jersey, United States, 08691
Cardio Metabolic Institute
Somerset, New Jersey, United States, 08873
Holy Name Medical Center, Inc.
Teaneck, New Jersey, United States, 07666
Total Cardiology Care, LLC
Wayne, New Jersey, United States, 07470
Westwood Cardiology Associates
Westwood, New Jersey, United States, 07675
United States, New Mexico
Presbyterian Heart Group
Albuquerque, New Mexico, United States, 87106
United States, New York
Albany Medical College
Albany, New York, United States, 12208
Albany Stratton VA Medical Center
Albany, New York, United States, 12208
Novel Research of New York, LLC
Bronx, New York, United States, 10461
Montefiore Medical Center
Bronx, New York, United States, 10467
Brown - SUNY Downstate Medical Center
Brooklyn, New York, United States, 11203
Buffalo Heart Group
Buffalo, New York, United States, 14215
Bassett Healthcare Network
Cooperstown, New York, United States, 13326
NYU Hudson Valley Cardiology
Cortlandt Manor, New York, United States, 10567
NYHQ
Flushing, New York, United States, 11355
Jamaica Hospital Medical Center
Jamaica, New York, United States, 11418
Long Island Heart Associates
Mineola, New York, United States, 11501
Winthrop University Hospital
Mineola, New York, United States, 11501
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Queens Long Island Medical Group
New Hyde Park, New York, United States, 11577
Chinatown Cardiology, PC
New York, New York, United States, 10013
Weill Cornell Medical College and NY Presbyterian
New York, New York, United States, 10021
Mount Sinai School of Medicine
New York, New York, United States, 10029
DiGiovanna Institute for Medical Education and Research
North Massapequa, New York, United States, 11758
Champlain Valley Physician Hospital
Plattsburgh, New York, United States, 12901
Cardiology Associates of Schenectady
Schenectady, New York, United States, 12309
United States, North Carolina
Clinical Study Center of Asheville
Asheville, North Carolina, United States, 28801
Metrolina Internal Medicine
Charlotte, North Carolina, United States, 28204
Gaffney Health Services
Charlotte, North Carolina, United States, 28205
Carolinas Research Center
Charlotte, North Carolina, United States, 28215
Eastern Carolina Cardiovascular, PA
Elizabeth City, North Carolina, United States, 27909
Eastern Cardiology
Greenville, North Carolina, United States, 27834
Northside Clinical Research
Lenoir, North Carolina, United States, 28645
Lake Shore Clinical Research, LLC.
Mooresville, North Carolina, United States, 28117
Carteret Medical Group
Morehead City, North Carolina, United States, 28557
Cardiology Associates of Carolinas, PA
Morganton, North Carolina, United States, 28655
Eastern Nephrology Associates, PLLC
New Bern, North Carolina, United States, 28562
Boice Willis Clinic
Rocky Mount, North Carolina, United States, 27804
Sanford Cardiology
Sanford, North Carolina, United States, 27330
Natalie A. Doyle, MD, PA
Wilson, North Carolina, United States, 27893
United States, North Dakota
Altru Health System Rehab Center
Grand Forks, North Dakota, United States, 58201
United States, Ohio
Akron General Medical Center
Akron, Ohio, United States, 44307
Ohio University Heritage College of Osteopathic Medicine
Athens, Ohio, United States, 45701
Diabetes and Endocrinology Associates of Stark Cit
Canton, Ohio, United States, 44718
The Lindner Research Center
Cincinnati, Ohio, United States, 45219
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Optimed Research, LTD
Columbus, Ohio, United States, 43235
Dayton Heart Center
Dayton, Ohio, United States, 45414
Dayton Veteran Affairs Medical Center
Dayton, Ohio, United States, 45428
Colonnade Medical Group
Lancaster, Ohio, United States, 43130
Middletown Cardiovascular Associates
Middletown, Ohio, United States, 45044
Comprehensive Heart Care, Inc.
Toledo, Ohio, United States, 43606
Mount Carmel Clinical Cardiovascular Care
Westerville, Ohio, United States, 43081
Premier Physicians
Westlake, Ohio, United States, 44154
Wooster Heart Group
Wooster, Ohio, United States, 44691
United States, Oklahoma
Unity Clinical Research
Lindsay, Oklahoma, United States, 73052
COR Clinical Research, LLC
Oklahoma City, Oklahoma, United States, 73103
Thadani - VA Medical Center Oklahoma City, OK
Oklahoma City, Oklahoma, United States, 73104
Today Clinical Research
Oklahoma City, Oklahoma, United States, 73129
Cardiovascular Health Clinic
Oklahoma City, Oklahoma, United States, 73134
Oklahoma State University Center for Health Sciences
Tulsa, Oklahoma, United States, 74127
United States, Oregon
Samaritan Health Services
Corvallis, Oregon, United States, 97330
Southern Oregon Cardiology, LLC
Medford, Oregon, United States, 97504
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Center for Clinical Res. Abington Health
Abington, Pennsylvania, United States, 19001
St. Luke's University Hospital
Bethlehem, Pennsylvania, United States, 18018
Renu-Ca Research Institute, Lower Bucks Hospital
Bristol, Pennsylvania, United States, 19007
Main Line Health Center, Broomall
Broomall, Pennsylvania, United States, 19008
Spirit Physician Services, Inc
Camp Hill, Pennsylvania, United States, 17011
The Chambersburg Hospital
Chambersburg, Pennsylvania, United States, 17201
Central Bucks Cardiology
Doylestown, Pennsylvania, United States, 18901
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
Heart Specialists of Lancaster County
Ephrata, Pennsylvania, United States, 17522
Saint Vincent Consultants in Cardiovascular Diseases, LLC
Erie, Pennsylvania, United States, 16502
Feasterville Family Healthcare Center
Feasterville, Pennsylvania, United States, 19053
Christiana Care Health System
Glen Mills, Pennsylvania, United States, 19342
Pinnacle Health Cardiovascular Institute
Harrisburg, Pennsylvania, United States, 17110
George Isajiw, MD
Lansdowne, Pennsylvania, United States, 19050
Bucks County Clinical Research
Morrisville, Pennsylvania, United States, 19067
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19102
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Lehigh Valley Health Services
Sellersville, Pennsylvania, United States, 18960
Pish Medical Associates, Inc.
Uniontown, Pennsylvania, United States, 15401
Lehigh Valley Family Practice
Whitehall, Pennsylvania, United States, 18052
Wilkes-Barre VA Medical Center
Wilkes-Barre, Pennsylvania, United States, 18711
United States, Rhode Island
Partners in Clinical Research
Cumberland, Rhode Island, United States, 02864
Ocean State Clinical Research Prtnr
Lincoln, Rhode Island, United States, 02865
Memorial Hospital of Rhode Island
Pawtucket, Rhode Island, United States, 02860
The Miriam Hospital
Providence, Rhode Island, United States, 02906
Ocean State Research Institute, Inc
Providence, Rhode Island, United States, 02908
United States, South Carolina
South Carolina Heart Center
Columbia, South Carolina, United States, 29204
Amistad Research Center, LLC
Columbia, South Carolina, United States, 29223
Charlotte Hearts
Indian Land, South Carolina, United States, 29707
Miller - SC Internal Medicine Associates.: Irmo
Irmo, South Carolina, United States, 29063
Inlet Cardiopulmonary & Associates
Pawleys Island, South Carolina, United States, 29585
Fusion Clinical Research of Spartanburg
Spartanburg, South Carolina, United States, 29301
Palmetto Research Center, LLC
Spartanburg, South Carolina, United States, 29302
United States, Tennessee
New Phase Research & Development
Chattanooga, Tennessee, United States, 37409
Parkway Medical Group
Fayetteville, Tennessee, United States, 37334
Stern Cardiovascular Foundation, Inc.
Germantown, Tennessee, United States, 38138
Kore Cardiovascular Research Institutue
Jackson, Tennessee, United States, 38305
New Phase Research & Development
Knoxville, Tennessee, United States, 37909
Cardiovascular Research of Knoxville
Knoxville, Tennessee, United States, 37917
Ramanathan - VAMC Memphis
Memphis, Tennessee, United States, 38104
Clinical Research Center Meharry Medical College
Nashville, Tennessee, United States, 37208
United States, Texas
Avant Research Associates LLC
Austin, Texas, United States, 78704
Texas Heart and Vascular Research, LLC
Austin, Texas, United States, 78745
Southeast TX Clinical Research Center
Beaumont, Texas, United States, 77702
Cornerstone Family Medicine
Big Spring, Texas, United States, 79720
IMD Medical Center
Carrollton, Texas, United States, 75006
Texas Health Physicians Group
Carrollton, Texas, United States, 75010
Cardiovascular Research Institute of Dallas
Dallas, Texas, United States, 75231
North Texas Health Center
Dallas, Texas, United States, 75231
The Heart Center of Dallas
Dallas, Texas, United States, 75235
Global Medical Research
DeSoto, Texas, United States, 75115
The Medical Group of Texas
Fort Worth, Texas, United States, 76104
Texas Health Physicians Group
Fort Worth, Texas, United States, 76107
T&R Clinic, P.A.
Haltom City, Texas, United States, 76117
Michele P. Sartori, MD
Houston, Texas, United States, 77030
Grand Medical Care
Katy, Texas, United States, 77494
Team Research Of Central Texas
Killeen, Texas, United States, 76543
Houston Heart and Vascular Associates
Kingwood, Texas, United States, 77339
Grace Research, LLC
Marshall, Texas, United States, 75670
Valley Heart Consultants
McAllen, Texas, United States, 78503
Heart Center, Palo Pinto General Hospital
Mineral Wells, Texas, United States, 76067
Valley Central Research Inc
Mission, Texas, United States, 78572
North Hills Medical Research, Inc
North Richland Hills, Texas, United States, 76180
Grace Research, LLC
Palestine, Texas, United States, 75801
Avant Research Associates, LLC
Port Arthur, Texas, United States, 77640
Santoscoy - Health Texas Research Institute
San Antonio, Texas, United States, 78212
Element Research Group
San Antonio, Texas, United States, 78229
Schnitzler Cardiovascular Consultants
San Antonio, Texas, United States, 78229
San Antonio Endovascular & Heart Institute
San Antonio, Texas, United States, 78268
Acacia Medical Research Institute
Sugar Land, Texas, United States, 77478
Health Plus Clinical Research
Sugar Land, Texas, United States, 77478
Lone Star Heart and Vascular Center
Tomball, Texas, United States, 77375
Northwest Houston Clinical Research
Tomball, Texas, United States, 77375
Hillcrest Family Health Center
Waco, Texas, United States, 76710
United States, Utah
Utah Cardiology, P.C.
Layton, Utah, United States, 84041
Utah Diabetes Center
Salt Lake City, Utah, United States, 84108
United States, Vermont
VA Medical Center, White River Junction
White River Junction, Vermont, United States, 05009
United States, Virginia
Burke Internal Medicine & Research
Burke, Virginia, United States, 22015
Seven Corners Medical Research Center
Falls Church, Virginia, United States, 22044
Hampton Family Practice Research
Hampton, Virginia, United States, 23666
Tidewater Physicians Multispecialty Group
Hampton, Virginia, United States, 23666
Virginia Cardiovascular Associates
Manassas, Virginia, United States, 20109
Manassas Clinical Research Center
Manassas, Virginia, United States, 20110
Tucker Cardiology Associates, P.C.
Mechanicsville, Virginia, United States, 23116
TPMG Clinical Research
Newport News, Virginia, United States, 23606
Sentara Norfolk General Hospital
Norfolk, Virginia, United States, 23507
Roanoke Heart Institute PLC
Roanoke, Virginia, United States, 24014
Cardinal Internal Medicine Associates
Woodbridge, Virginia, United States, 22192
Tidewater Physicians Multispecialty Group
Yorktown, Virginia, United States, 23690
United States, Washington
Frandsen Family Medicine DBA Sound Medi
Port Orchard, Washington, United States, 98366
Premier Clinical Research
Spokane, Washington, United States, 99202
Kootenai Heart Clinics, LLC
Spokane, Washington, United States, 99204
Northside Internal Medicine
Spokane, Washington, United States, 99208
Northwest Medical Associates, P.S.
Vancouver, Washington, United States, 98684
United States, Wisconsin
Cardiology Associates of Bellin Health
Green Bay, Wisconsin, United States, 54115
Dean Foundation
Madison, Wisconsin, United States, 53715
University Of Wisconsin
Madison, Wisconsin, United States, 53715
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Columbia St. Mary's
Milwaukee, Wisconsin, United States, 53211
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Canada, British Columbia
The Medical Arts Health Research Group
North Vancouver, British Columbia, Canada, V7M 2H4
The Medical Arts Health Research Group
Penticton, British Columbia, Canada, V2A 5C8
Canada, Manitoba
Winnipeg Clinic
Winnipeg, Manitoba, Canada, R3C 0N2
Canada, Ontario
Bramalea Medical Centre
Brampton, Ontario, Canada, L6T 4S5
Brampton Research Associates
Brampton, Ontario, Canada, L6Z 4N5
Philippe R Beaudry Medicine Professional Corporation
Burlington, Ontario, Canada, L7R 4E2
Vizel Cardiac Research
Cambridge, Ontario, Canada, N1R7R1
Dr. Linda Sinnaeve's Office
Chatham, Ontario, Canada, N7L 1C1
Scisco Clinical Research
Cornwall, Ontario, Canada, K6H 4M4
Dr. Peter Spadafora Health Center
Guelph, Ontario, Canada, N1E 5G6
John Stimac, MD
Hamilton, Ontario, Canada, L8L 5G4
KMH Cardiology & Diagnostics: Hamilton
Hamilton, Ontario, Canada, L8P 3A9
Dr. William Liang
Hamilton, Ontario, Canada, L8W3J6
Source Unique Clinic
Hawkesbury, Ontario, Canada, K6A 1A1
Dr. Ronald Fowlis
Kitchener, Ontario, Canada, N2M 5NG
University Hospital
London, Ontario, Canada, N6A 5A5
Malton Medical Research
Mississauga, Ontario, Canada, L4T 4J2
KMH Cardiology & Diagnostics: Mississauga
Mississauga, Ontario, Canada, L5K 2L3
Sewa Ram Singal Medicine Professional Corporation
Mississauga, Ontario, Canada, L5U 0A6
Newmarket Cardiology Research Group
Newmarket, Ontario, Canada, l3y -8c3
Newmarket Cardiology Research Group
Newmarket, Ontario, Canada, L3Y 8C3
Portage Medical Centre
Niagra Falls, Ontario, Canada, I2E6A6
Humber River Regional Hospital
North York, Ontario, Canada, M3N2V6
Bakbak Medicine Professional Corporation
Oshawa, Ontario, Canada, L1H 1B9
Dr. James Y. Cha
Oshawa, Ontario, Canada, L1J2K1
University Of Ottawa Heart Institute
Ottawa, Ontario, Canada, k1y -4w7
Kawartha Cardiology Clinical Trials
Peterborough, Ontario, Canada, K9J0B2
Steeple Hill Medical Centre
Pickering, Ontario, Canada, L1V 2A6
Sarnia Institute Of Clinical Research
Sarnia, Ontario, Canada, N7T 4X3
Scarborough Cardiology Research
Scarborough, Ontario, Canada, M1E5E9
Scarborough General Hospital Cardiology Research Associates
Scarborough, Ontario, Canada, M1PT27
Milliken Medical Centre
Scarborough, Ontario, Canada, M1V5P6
Canadian Centre for Research on Diabetes
Smith Falls, Ontario, Canada, K7A 4W8
Lake Shore Cardiology
St. Catharines, Ontario, Canada, L2S 2Y3
Sardar Medical Clinic
St. Thomas, Ontario, Canada, N5R 2R4
G.S. Cardiac Lab Medicine Professional Corp
Sudbury, Ontario, Canada, P3C 1S8
Dr. R. Labonte Professional Med Corp
Sudbury, Ontario, Canada, P3E 3B8
Dr. G. Garrioch, Independent Practice
Sudbury, Ontario, Canada, P3E 3C6
Dr. Laurence Gibbs Medicine Professional Corp.
Thedford, Ontario, Canada, N0M 2N0
Tillsonburg Medical Centre
Tillsonburg, Ontario, Canada, N4G 5A7
Humber River Hospital
Toronto, Ontario, Canada, M3M 0B2
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
St. Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Weston Road Medical Clinic
Toronto, Ontario, Canada, M9N 2A7
Dr. Nigel Jagan Medicine Professional Corporation
Whitby, Ontario, Canada, L1N 2L1
Dr. Nwadiaro Medicine Professional Corp
Windsor, Ontario, Canada, N8X 1L9
Canada, Quebec
Viacar Recherche Clinique Inc.
Brossard, Quebec, Canada, J4X1S4
Ecogene-21
Chicoutimi, Quebec, Canada, G7H 7K9
Q&T Research Chicoutimi
Chicoutimi, Quebec, Canada, G7H 7Y8
Viacar Recherche Clinique Inc.
Greenfield Park, Quebec, Canada, J4V2G8
CHUM Hotel-Dieu
Montreal, Quebec, Canada, H2W 1T8
Iucpq
Quebec City, Quebec, Canada, G1V 4G5
ALPHA Recherche Clinique
Québec, Quebec, Canada, G3K 2P8
CardioVasc HR
Saint-Jean-sur-Richelieu, Quebec, Canada, j3a-1c3
ViaCar Recherche Clinique Inc
Saint-Lambert, Quebec, Canada, J4P 2H4
Viacar Recherche Clinique
St. Lambert, Quebec, Canada, J4P 2J2
Hopital Pierre-Le Gardeur
Terrebonne, Quebec, Canada, J6V 2H2
Canada
Recherche Clinique Sigma, Inc.
Quebec, Canada, G1G3Z4
Puerto Rico
Instituto Sanacoop
Bayamón, Puerto Rico, 00961
San Juan Bautista School of Medicine
Caguas, Puerto Rico, 00727
Norma S. Severino-Pacheco, MD
Canovanas, Puerto Rico, 00729
Cardiometabolic Research Center
Ponce, Puerto Rico, 00717
Miguel Sosa-Padilla, MD
San Juan, Puerto Rico, 00926-2832
Yolanda Sierra Quinones, MD
Toa Baja, Puerto Rico, 00949
Sponsors and Collaborators
Brigham and Women's Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Paul Ridker, MD, MPH Brigham and Women's Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Paul Ridker, Director, Center for Cardiovascular Disease and Prevention, Brigham and Women's Hospital, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01594333     History of Changes
Other Study ID Numbers: 2012P-000857
U01HL101422 ( U.S. NIH Grant/Contract )
U01HL101389 ( U.S. NIH Grant/Contract )
First Posted: May 9, 2012    Key Record Dates
Last Update Posted: April 5, 2018
Last Verified: April 2018

Keywords provided by Paul Ridker, Brigham and Women's Hospital:
Myocardial Infarction
Stroke
Cardiovascular death
Type 2 Diabetes
Metabolic Syndrome
Cardiovascular Inflammation
Atherothrombosis

Additional relevant MeSH terms:
Cardiovascular Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors