MedPath

Cardiovascular Inflammation Reduction Trial

Phase 3
Completed
Conditions
Cardiovascular Disease
Interventions
Drug: Placebo
Registration Number
NCT01594333
Lead Sponsor
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).

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
4786
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 Cockcroft-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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo: Tablet, Oral weekly plus 1.0mg folic acid 6 days/week
MethotrexateMethotrexateMethotrexate: Tablet, Oral, Target dose 15-20mg weekly plus 1.0 mg folic acid 6 days/week
Primary Outcome Measures
NameTimeMethod
Number of Subjects With Major Adverse Cardiovascular EventsFrom randomization to trial end (April 2, 2018) up to a maximum of 5 years

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.

Number of Subjects With Major Adverse Cardiovascular Event or Hospitalization for Unstable Angina That Led to Urgent Coronary RevascularizationFrom randomization to trial end (April 2, 2018) - up to a maximum of 5 years

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

Secondary Outcome Measures
NameTimeMethod
Number of Subjects With Major Adverse Cardiovascular Event or Any Coronary RevascularizationFrom randomization to the trial end (April 2, 2018) - up to a maximum of 5 years

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

Number of Subjects With New Onset Type 2 DiabetesFrom randomization to the trial end (April 2, 2018) - up to 5 years

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.

Number of Subjects With All-cause MortalityFrom randomization to the trial end (April 2, 2018) up to a maximum of 5 years

Subjects who died from any cause.

Number of Subjects With Hospitalization for Congestive Heart FailureFrom randomization to trial end (April 2, 2018) up to a maximum of 5 years

The first occurrence of Hospitalization for Congestive Heart Failure

Number of Subjects With Major Adverse Cardiovascular Event, Coronary Revascularization, Hospitalization for Congestive Heart Failure or All Cause MortalityFrom randomization to trial end (April 2, 2018) up to a maximum of 5 years

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

Trial Locations

Locations (458)

Team Medical Research

🇺🇸

Miami, Florida, United States

Indiana Heart Physicians

🇺🇸

Indianapolis, Indiana, United States

Sanitas Research

🇺🇸

Miami, Florida, United States

South Florida Research Group, LLC

🇺🇸

Miami, Florida, United States

Vista Health Research, LLC

🇺🇸

Miami, Florida, United States

Segui - Med Care Research

🇺🇸

Miami, Florida, United States

D De La Vega MD Research Group

🇺🇸

Miami, Florida, United States

Appalachian Research Associates

🇺🇸

Fort Payne, Alabama, United States

Saadat Ansari MD LLC

🇺🇸

Huntsville, Alabama, United States

Avant Research Associates, LLC

🇺🇸

Port Arthur, Texas, United States

University of South Alabama: Division of Clinical Research

🇺🇸

Mobile, Alabama, United States

The Heart Clinic

🇺🇸

Scottsdale, Arizona, United States

Arkansas Heart Hospital

🇺🇸

Little Rock, Arkansas, United States

Touro University California- Solano County Affiliated Clinics

🇺🇸

Fairfield, California, United States

Arkansas Cardiology

🇺🇸

Little Rock, Arkansas, United States

Oracle Clinical Research, Inc.

🇺🇸

Anaheim, California, United States

Medical Group of Culver City

🇺🇸

Culver City, California, United States

University Of California San Francisco

🇺🇸

Fresno, California, United States

VACCHCS

🇺🇸

Fresno, California, United States

UCSD Sulpizio Cardiovascular Center

🇺🇸

La Jolla, California, United States

Desert Medical Care & Wellness

🇺🇸

La Quinta, California, United States

Kumar Medical Corporation

🇺🇸

Lancaster, California, United States

VA Loma Linda Healthcare System

🇺🇸

Loma Linda, California, United States

Long Beach Center for Clinical Research

🇺🇸

Long Beach, California, United States

Cardiovascular Innovation and Research

🇺🇸

Long Beach, California, United States

Loma Linda University Health

🇺🇸

Loma Linda, California, United States

Los Alamitos Cardiovascular

🇺🇸

Los Alamitos, California, United States

Faye Montegrande Md. Clinical Research

🇺🇸

Los Angeles, California, United States

Salman Khan A. Medical Corporation

🇺🇸

Los Angeles, California, United States

West LA VA Medical Center

🇺🇸

Los Angeles, California, United States

VA Northern California Health Care

🇺🇸

Mather, California, United States

Orange County Heart Institute & Research

🇺🇸

Orange, California, United States

Diverse Research Solutions

🇺🇸

Oxnard, California, United States

University of CA Irvine Medical Center

🇺🇸

Orange, California, United States

Central Coast Cardiology

🇺🇸

Salinas, California, United States

Pacific Heart and Vascular Medical Group

🇺🇸

Stockton, California, United States

Coastal Heart Medical Group, Inc.

🇺🇸

Santa Ana, California, United States

Comprehensive Cardiovascular Care

🇺🇸

Santa Maria, California, United States

Munni R. Selagamsetty, Md, Pc

🇺🇸

Colorado Springs, Colorado, United States

Touro University California- Solano Public Health Affiliated Clinics

🇺🇸

Vallejo, California, United States

Manoj D. Aswani M.D.

🇺🇸

Thousand Oaks, California, United States

Colorado Health Medical Group Heart Center of the Rockies

🇺🇸

Fort Collins, Colorado, United States

Unrein - Rocky Vista University Health Center

🇺🇸

Parker, Colorado, United States

Medical Center of the Rockies Research

🇺🇸

Fort Collins, Colorado, United States

Connecticut Heart and Vascular Center

🇺🇸

Bridgeport, Connecticut, United States

Bridgeport Hospital

🇺🇸

Bridgeport, Connecticut, United States

Boisey Barnes MD, PC

🇺🇸

Washington, District of Columbia, United States

Gonzalez MD & Aswad MD Health Ser

🇺🇸

Coral Gables, Florida, United States

Pianko - Aventura Research Center, LLC

🇺🇸

Aventura, Florida, United States

St. Francis Medical Institute

🇺🇸

Clearwater, Florida, United States

Seidman Clinical Trials

🇺🇸

Delray Beach, Florida, United States

American Research Institute, Inc.

🇺🇸

Cutler Bay, Florida, United States

Daytona Heart Group

🇺🇸

DeLand, Florida, United States

Steven Cohen MD

🇺🇸

Delray Beach, Florida, United States

Infinite Clinical Research

🇺🇸

Doral, Florida, United States

Invesclinic

🇺🇸

Fort Lauderdale, Florida, United States

Lake Internal Medicine Assocaties

🇺🇸

Eustis, Florida, United States

International Research Partners, LLC

🇺🇸

Doral, Florida, United States

Medical Research Institute at Doral, Inc.

🇺🇸

Doral, Florida, United States

Primary Care Associates

🇺🇸

Fort Myers, Florida, United States

Lee Physician Group

🇺🇸

Fort Myers, Florida, United States

Qway Research

🇺🇸

Hialeah, Florida, United States

Healing Touch C&C Research

🇺🇸

Hialeah, Florida, United States

State of the Art Research

🇺🇸

Hialeah, Florida, United States

Viviana Perez MD Research & Cosmetics

🇺🇸

Hialeah, Florida, United States

Luzmed Clinical Research Institute

🇺🇸

Hialeah, Florida, United States

Nova Clinical Research Clinic

🇺🇸

Hialeah, Florida, United States

Elite Cardiac Research Center LLC

🇺🇸

Hialeah, Florida, United States

South Florida Research Solutions, LLC

🇺🇸

Hollywood, Florida, United States

Best Quality Research, Inc.

🇺🇸

Hialeah, Florida, United States

Hope Clinical Research

🇺🇸

Kissimmee, Florida, United States

Cardiovascular Medical Associates of Palm Beach

🇺🇸

Jupiter, Florida, United States

SIH Research, LLC

🇺🇸

Kissimmee, Florida, United States

Lakes Research, LLC

🇺🇸

Miami Lakes, Florida, United States

Ocean Blue Medical Research Center

🇺🇸

Miami Springs, Florida, United States

Veritas Research Corp.

🇺🇸

Miami Lakes, Florida, United States

St. Paul Medical Research Center, Inc.

🇺🇸

Miami, Florida, United States

Medical Research Center of Florida

🇺🇸

Miami, Florida, United States

LG Diagnostics, Inc.

🇺🇸

Miami, Florida, United States

Paradise Clinical Research, LLC

🇺🇸

Miami, Florida, United States

GAD Research Center

🇺🇸

Miami, Florida, United States

Innovation Research Institute, Inc.

🇺🇸

Miami, Florida, United States

Southwest Florida Research, LLC

🇺🇸

Naples, Florida, United States

Palm Beach Gardens Research Center, LLC

🇺🇸

Palm Beach Gardens, Florida, United States

Broward Research Center

🇺🇸

Pembroke Pines, Florida, United States

Pioneer Clinical Research

🇺🇸

Pembroke Pines, Florida, United States

Richard G. Friedman, MD

🇺🇸

San Diego, California, United States

Ritchken and First MDs

🇺🇸

San Diego, California, United States

Foundation for Cardiovascular Medicine

🇺🇸

San Diego, California, United States

San Diego Cardiac Center

🇺🇸

San Diego, California, United States

Veterans Affairs San Diego Healthcare System

🇺🇸

San Diego, California, United States

Bay Area Heart Center: 49th Street

🇺🇸

Saint Petersburg, Florida, United States

Sandoval - Broward Research Center

🇺🇸

Pembroke Pines, Florida, United States

Bay Area Heart Center: 7th Avenue

🇺🇸

Saint Petersburg, Florida, United States

Lenus Research & Medical Group

🇺🇸

Sweetwater, Florida, United States

DBC Research

🇺🇸

Tamarac, Florida, United States

Asclepes Research Centers

🇺🇸

Weeki Wachee, Florida, United States

Gupta - Premier Heart and Vascular Center

🇺🇸

Wesley Chapel, Florida, United States

Atlanta Veterans Affairs Medical Center

🇺🇸

Atlanta, Georgia, United States

Athens Regional Medical Center

🇺🇸

Athens, Georgia, United States

Laureate Medical Group at Northside

🇺🇸

Atlanta, Georgia, United States

Synergy Therapeutic Partners

🇺🇸

Atlanta, Georgia, United States

Northside Hospital

🇺🇸

Atlanta, Georgia, United States

Atlanta Heart Specialists, LLC

🇺🇸

Tucker, Georgia, United States

Heart and Rhythm Specialists

🇺🇸

Dalton, Georgia, United States

Albert F. Johary MD, PC

🇺🇸

Dunwoody, Georgia, United States

Infinite Clinical Trials

🇺🇸

Riverdale, Georgia, United States

Atlanta Vanguard Medical Associates

🇺🇸

Smyrna, Georgia, United States

Herman Clinical Research, LLC

🇺🇸

Suwanee, Georgia, United States

Cardiology Associates of Vidalia, P.C.

🇺🇸

Vidalia, Georgia, United States

St. Luke's Idaho Cardiology Associates

🇺🇸

Boise, Idaho, United States

Clinical Research Prime

🇺🇸

Idaho Falls, Idaho, United States

Northwest Heart Clinical Research

🇺🇸

Arlington Heights, Illinois, United States

Advocate Med Group-Heart & Vascular Of Illinois

🇺🇸

Chicago, Illinois, United States

Captain James A. Lovell Federal Health

🇺🇸

North Chicago, Illinois, United States

Illinois Heart & Lung Research Center, SC

🇺🇸

Normal, Illinois, United States

University of Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

Specialty Physicians of Illinois, LLC

🇺🇸

Olympia Fields, Illinois, United States

Cardiospecialists, LTD

🇺🇸

Dyer, Indiana, United States

Advanced CardioVascular Consultants

🇺🇸

Rock Island, Illinois, United States

Martin - Martin Family Practice and Research

🇺🇸

Evansville, Indiana, United States

Krannert Institute Of Cardiology

🇺🇸

Indianapolis, Indiana, United States

Community Hospital South

🇺🇸

Indianapolis, Indiana, United States

Medical Consultants, PC

🇺🇸

Muncie, Indiana, United States

Iowa Heart Center

🇺🇸

West Des Moines, Iowa, United States

Research Integrity LLC

🇺🇸

Owensboro, Kentucky, United States

Dorothy H. Banish, MD, APMC Study Group

🇺🇸

Covington, Louisiana, United States

American Clinical Research, LLC

🇺🇸

Marrero, Louisiana, United States

Otis Barnum D.O.P.C.

🇺🇸

Natchitoches, Louisiana, United States

Paul A. Shapero, M.D.

🇺🇸

Bangor, Maine, United States

Maine Medical Partners Maine Health Cardiology

🇺🇸

South Portland, Maine, United States

Southern Maine Health Care

🇺🇸

Biddeford, Maine, United States

Sinai Center for Thrombosis Research

🇺🇸

Baltimore, Maryland, United States

St. Mary's Medical Center

🇺🇸

Charlotte Hall, Maryland, United States

Calvert Memorial Hospital

🇺🇸

Clinton, Maryland, United States

IRC Clinics

🇺🇸

Towson, Maryland, United States

Peninsula Cardiology Associates

🇺🇸

Salisbury, Maryland, United States

Shah Associates, MD, LLC

🇺🇸

Prince Frederick, Maryland, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

St. Elizabeth's Medical Center

🇺🇸

Boston, Massachusetts, United States

MGH Cardiology

🇺🇸

Boston, Massachusetts, United States

Lahey Hospital and Medical Center

🇺🇸

Burlington, Massachusetts, United States

Massachusetts General Hospital - Chelsea Health Care Center

🇺🇸

Chelsea, Massachusetts, United States

VA Central Western Massachusetts Healthca

🇺🇸

Leeds, Massachusetts, United States

Pentucket Medical Associates, Inc.

🇺🇸

Haverhill, Massachusetts, United States

South Shore Internal Medicine

🇺🇸

Milton, Massachusetts, United States

Lahey Medical Center

🇺🇸

Peabody, Massachusetts, United States

North Shore Cardiovascular Associates

🇺🇸

Salem, Massachusetts, United States

Reliant Medical Group

🇺🇸

Worcester, Massachusetts, United States

Apex Medical Research MI, Inc.

🇺🇸

Flint, Michigan, United States

Flint Clinical Research

🇺🇸

Flint, Michigan, United States

Garden City Hospital

🇺🇸

Garden City, Michigan, United States

Genesys Regional Medical Center

🇺🇸

Grand Blanc, Michigan, United States

Academic Cardiology Associates PC

🇺🇸

Rochester Hills, Michigan, United States

National Clinical LLC

🇺🇸

Hamtramck, Michigan, United States

Beaumont Health Center

🇺🇸

Royal Oak, Michigan, United States

Covenant Medical Center, Inc.

🇺🇸

Saginaw, Michigan, United States

Mid-Michigan Heart & Vascular Center

🇺🇸

Saginaw, Michigan, United States

Centra Care Heart & Vascular Center at St. Cloud Hospital

🇺🇸

Saint Cloud, Minnesota, United States

United Heart and Vascular Clinic

🇺🇸

Saint Paul, Minnesota, United States

David M. Headley M.D. PA Planters Clinic

🇺🇸

Port Gibson, Mississippi, United States

Center for Advanced Medicine and Research LLC

🇺🇸

Bridgeton, Missouri, United States

Clinical Research Center University of Missouri

🇺🇸

Columbia, Missouri, United States

Quantum Research LLC

🇺🇸

Festus, Missouri, United States

Midwest Cardiology Associates

🇺🇸

Independence, Missouri, United States

Freeman Health System

🇺🇸

Joplin, Missouri, United States

VA St. Louis Health Care System (VASTLHCS)

🇺🇸

Saint Louis, Missouri, United States

Lake Regional Cardiovascular Institute

🇺🇸

Osage Beach, Missouri, United States

SLUCare Cardiology

🇺🇸

Saint Louis, Missouri, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

Clinical Investigators LLC

🇺🇸

Saint Louis, Missouri, United States

Consult and Research Associates

🇺🇸

Saint Louis, Missouri, United States

CoxHealth: Wheeler Heart & Vascular Center

🇺🇸

Springfield, Missouri, United States

Center for Advanced Medicine and Research

🇺🇸

Saint Peters, Missouri, United States

Cone - Montana Medical Research

🇺🇸

Missoula, Montana, United States

Mercy Medical Research Institute

🇺🇸

Springfield, Missouri, United States

Barrett Clinic, P.C.

🇺🇸

La Vista, Nebraska, United States

Internal Medicine Clinic

🇺🇸

Las Vegas, Nevada, United States

Sierra Nevada Health Care System

🇺🇸

Reno, Nevada, United States

Red Rock Clinical Research, LLC

🇺🇸

Las Vegas, Nevada, United States

Renown Inst for Heart & Vasc Health

🇺🇸

Reno, Nevada, United States

Family Health at Mount Olive

🇺🇸

Flanders, New Jersey, United States

Cardiocare

🇺🇸

Hillsborough, New Jersey, United States

New Jersey Heart

🇺🇸

Linden, New Jersey, United States

Palisade Medical Center

🇺🇸

North Bergen, New Jersey, United States

Cardiovascular Institute

🇺🇸

New Brunswick, New Jersey, United States

Mercer Bucks Cardiology

🇺🇸

Robbinsville, New Jersey, United States

Holy Name Medical Center, Inc.

🇺🇸

Teaneck, New Jersey, United States

Total Cardiology Care, LLC

🇺🇸

Wayne, New Jersey, United States

Albany Medical College

🇺🇸

Albany, New York, United States

Albany Stratton VA Medical Center

🇺🇸

Albany, New York, United States

Brown - SUNY Downstate Medical Center

🇺🇸

Brooklyn, New York, United States

Buffalo Heart Group

🇺🇸

Buffalo, New York, United States

Bassett Healthcare Network

🇺🇸

Cooperstown, New York, United States

NYHQ

🇺🇸

Flushing, New York, United States

NYU Hudson Valley Cardiology

🇺🇸

Cortlandt Manor, New York, United States

Winthrop University Hospital

🇺🇸

Mineola, New York, United States

Long Island Heart Associates

🇺🇸

Mineola, New York, United States

Long Island Jewish Medical Center

🇺🇸

New Hyde Park, New York, United States

Queens Long Island Medical Group

🇺🇸

New Hyde Park, New York, United States

Chinatown Cardiology, PC

🇺🇸

New York, New York, United States

Weill Cornell Medical College and NY Presbyterian

🇺🇸

New York, New York, United States

Mount Sinai School of Medicine

🇺🇸

New York, New York, United States

Champlain Valley Physician Hospital

🇺🇸

Plattsburgh, New York, United States

DiGiovanna Institute for Medical Education and Research

🇺🇸

North Massapequa, New York, United States

Clinical Study Center of Asheville

🇺🇸

Asheville, North Carolina, United States

Cardiology Associates of Schenectady

🇺🇸

Schenectady, New York, United States

Gaffney Health Services

🇺🇸

Charlotte, North Carolina, United States

Carolinas Research Center

🇺🇸

Charlotte, North Carolina, United States

Lake Shore Clinical Research, LLC.

🇺🇸

Mooresville, North Carolina, United States

Northside Clinical Research

🇺🇸

Lenoir, North Carolina, United States

Eastern Carolina Cardiovascular, PA

🇺🇸

Elizabeth City, North Carolina, United States

Eastern Cardiology

🇺🇸

Greenville, North Carolina, United States

Carteret Medical Group

🇺🇸

Morehead City, North Carolina, United States

Eastern Nephrology Associates, PLLC

🇺🇸

New Bern, North Carolina, United States

Cardiology Associates of Carolinas, PA

🇺🇸

Morganton, North Carolina, United States

Boice Willis Clinic

🇺🇸

Rocky Mount, North Carolina, United States

Sanford Cardiology

🇺🇸

Sanford, North Carolina, United States

Natalie A. Doyle, MD, PA

🇺🇸

Wilson, North Carolina, United States

Akron General Medical Center

🇺🇸

Akron, Ohio, United States

The Lindner Research Center

🇺🇸

Cincinnati, Ohio, United States

Diabetes and Endocrinology Associates of Stark Cit

🇺🇸

Canton, Ohio, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Ohio University Heritage College of Osteopathic Medicine

🇺🇸

Athens, Ohio, United States

Optimed Research, LTD

🇺🇸

Columbus, Ohio, United States

Colonnade Medical Group

🇺🇸

Lancaster, Ohio, United States

Middletown Cardiovascular Associates

🇺🇸

Middletown, Ohio, United States

Comprehensive Heart Care, Inc.

🇺🇸

Toledo, Ohio, United States

Mount Carmel Clinical Cardiovascular Care

🇺🇸

Westerville, Ohio, United States

Premier Physicians

🇺🇸

Westlake, Ohio, United States

Unity Clinical Research

🇺🇸

Lindsay, Oklahoma, United States

Wooster Heart Group

🇺🇸

Wooster, Ohio, United States

Oklahoma State University Center for Health Sciences

🇺🇸

Tulsa, Oklahoma, United States

Samaritan Health Services

🇺🇸

Corvallis, Oregon, United States

Southern Oregon Cardiology, LLC

🇺🇸

Medford, Oregon, United States

Main Line Health Center, Broomall

🇺🇸

Broomall, Pennsylvania, United States

Center for Clinical Res. Abington Health

🇺🇸

Abington, Pennsylvania, United States

Renu-Ca Research Institute, Lower Bucks Hospital

🇺🇸

Bristol, Pennsylvania, United States

St. Luke's University Hospital

🇺🇸

Bethlehem, Pennsylvania, United States

Spirit Physician Services, Inc

🇺🇸

Camp Hill, Pennsylvania, United States

The Chambersburg Hospital

🇺🇸

Chambersburg, Pennsylvania, United States

Central Bucks Cardiology

🇺🇸

Doylestown, Pennsylvania, United States

Saint Vincent Consultants in Cardiovascular Diseases, LLC

🇺🇸

Erie, Pennsylvania, United States

Heart Specialists of Lancaster County

🇺🇸

Ephrata, Pennsylvania, United States

Altoona Center for Clinical Research

🇺🇸

Duncansville, Pennsylvania, United States

Feasterville Family Healthcare Center

🇺🇸

Feasterville, Pennsylvania, United States

Pinnacle Health Cardiovascular Institute

🇺🇸

Harrisburg, Pennsylvania, United States

George Isajiw, MD

🇺🇸

Lansdowne, Pennsylvania, United States

Christiana Care Health System

🇺🇸

Glen Mills, Pennsylvania, United States

Bucks County Clinical Research

🇺🇸

Morrisville, Pennsylvania, United States

Drexel University College of Medicine

🇺🇸

Philadelphia, Pennsylvania, United States

Hospital of the University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Lehigh Valley Family Practice

🇺🇸

Whitehall, Pennsylvania, United States

Pish Medical Associates, Inc.

🇺🇸

Uniontown, Pennsylvania, United States

Lehigh Valley Health Services

🇺🇸

Sellersville, Pennsylvania, United States

Wilkes-Barre VA Medical Center

🇺🇸

Wilkes-Barre, Pennsylvania, United States

Ocean State Clinical Research Prtnr

🇺🇸

Lincoln, Rhode Island, United States

Partners in Clinical Research

🇺🇸

Cumberland, Rhode Island, United States

Memorial Hospital of Rhode Island

🇺🇸

Pawtucket, Rhode Island, United States

The Miriam Hospital

🇺🇸

Providence, Rhode Island, United States

Ocean State Research Institute, Inc

🇺🇸

Providence, Rhode Island, United States

South Carolina Heart Center

🇺🇸

Columbia, South Carolina, United States

Charlotte Hearts

🇺🇸

Indian Land, South Carolina, United States

Miller - SC Internal Medicine Associates.: Irmo

🇺🇸

Irmo, South Carolina, United States

Fusion Clinical Research of Spartanburg

🇺🇸

Spartanburg, South Carolina, United States

Inlet Cardiopulmonary & Associates

🇺🇸

Pawleys Island, South Carolina, United States

Palmetto Research Center, LLC

🇺🇸

Spartanburg, South Carolina, United States

New Phase Research & Development

🇺🇸

Knoxville, Tennessee, United States

Parkway Medical Group

🇺🇸

Fayetteville, Tennessee, United States

Kore Cardiovascular Research Institutue

🇺🇸

Jackson, Tennessee, United States

Cardiovascular Research of Knoxville

🇺🇸

Knoxville, Tennessee, United States

Ramanathan - VAMC Memphis

🇺🇸

Memphis, Tennessee, United States

Cornerstone Family Medicine

🇺🇸

Big Spring, Texas, United States

Southeast TX Clinical Research Center

🇺🇸

Beaumont, Texas, United States

IMD Medical Center

🇺🇸

Carrollton, Texas, United States

Texas Health Physicians Group

🇺🇸

Fort Worth, Texas, United States

The Heart Center of Dallas

🇺🇸

Dallas, Texas, United States

Cardiovascular Research Institute of Dallas

🇺🇸

Dallas, Texas, United States

North Texas Health Center

🇺🇸

Dallas, Texas, United States

Global Medical Research

🇺🇸

DeSoto, Texas, United States

The Medical Group of Texas

🇺🇸

Fort Worth, Texas, United States

Michele P. Sartori, MD

🇺🇸

Houston, Texas, United States

T&R Clinic, P.A.

🇺🇸

Haltom City, Texas, United States

Grand Medical Care

🇺🇸

Katy, Texas, United States

Team Research Of Central Texas

🇺🇸

Killeen, Texas, United States

Houston Heart and Vascular Associates

🇺🇸

Kingwood, Texas, United States

Grace Research, LLC

🇺🇸

Palestine, Texas, United States

Valley Heart Consultants

🇺🇸

McAllen, Texas, United States

Heart Center, Palo Pinto General Hospital

🇺🇸

Mineral Wells, Texas, United States

Valley Central Research Inc

🇺🇸

Mission, Texas, United States

North Hills Medical Research, Inc

🇺🇸

North Richland Hills, Texas, United States

Lone Star Heart and Vascular Center

🇺🇸

Tomball, Texas, United States

Acacia Medical Research Institute

🇺🇸

Sugar Land, Texas, United States

Health Plus Clinical Research

🇺🇸

Sugar Land, Texas, United States

Northwest Houston Clinical Research

🇺🇸

Tomball, Texas, United States

Hillcrest Family Health Center

🇺🇸

Waco, Texas, United States

Utah Cardiology, P.C.

🇺🇸

Layton, Utah, United States

Hampton Family Practice Research

🇺🇸

Hampton, Virginia, United States

Seven Corners Medical Research Center

🇺🇸

Falls Church, Virginia, United States

Burke Internal Medicine & Research

🇺🇸

Burke, Virginia, United States

Tidewater Physicians Multispecialty Group

🇺🇸

Yorktown, Virginia, United States

Manassas Clinical Research Center

🇺🇸

Manassas, Virginia, United States

TPMG Clinical Research

🇺🇸

Newport News, Virginia, United States

Virginia Cardiovascular Associates

🇺🇸

Manassas, Virginia, United States

Tucker Cardiology Associates, P.C.

🇺🇸

Mechanicsville, Virginia, United States

Sentara Norfolk General Hospital

🇺🇸

Norfolk, Virginia, United States

Frandsen Family Medicine DBA Sound Medi

🇺🇸

Port Orchard, Washington, United States

Roanoke Heart Institute PLC

🇺🇸

Roanoke, Virginia, United States

Cardinal Internal Medicine Associates

🇺🇸

Woodbridge, Virginia, United States

Premier Clinical Research

🇺🇸

Spokane, Washington, United States

Kootenai Heart Clinics, LLC

🇺🇸

Spokane, Washington, United States

Northwest Medical Associates, P.S.

🇺🇸

Vancouver, Washington, United States

Cardiology Associates of Bellin Health

🇺🇸

Green Bay, Wisconsin, United States

Northside Internal Medicine

🇺🇸

Spokane, Washington, United States

Marshfield Clinic

🇺🇸

Marshfield, Wisconsin, United States

The Medical Arts Health Research Group

🇨🇦

Penticton, British Columbia, Canada

Bramalea Medical Centre

🇨🇦

Brampton, Ontario, Canada

Brampton Research Associates

🇨🇦

Brampton, Ontario, Canada

Vizel Cardiac Research

🇨🇦

Cambridge, Ontario, Canada

Dr. Linda Sinnaeve's Office

🇨🇦

Chatham, Ontario, Canada

Philippe R Beaudry Medicine Professional Corporation

🇨🇦

Burlington, Ontario, Canada

Scisco Clinical Research

🇨🇦

Cornwall, Ontario, Canada

KMH Cardiology & Diagnostics: Hamilton

🇨🇦

Hamilton, Ontario, Canada

John Stimac, MD

🇨🇦

Hamilton, Ontario, Canada

Dr. Peter Spadafora Health Center

🇨🇦

Guelph, Ontario, Canada

Dr. William Liang

🇨🇦

Hamilton, Ontario, Canada

University Hospital

🇨🇦

London, Ontario, Canada

Dr. Ronald Fowlis

🇨🇦

Kitchener, Ontario, Canada

Malton Medical Research

🇨🇦

Mississauga, Ontario, Canada

KMH Cardiology & Diagnostics: Mississauga

🇨🇦

Mississauga, Ontario, Canada

Newmarket Cardiology Research Group

🇨🇦

Newmarket, Ontario, Canada

Portage Medical Centre

🇨🇦

Niagara Falls, Ontario, Canada

Humber River Regional Hospital

🇨🇦

North York, Ontario, Canada

Bakbak Medicine Professional Corporation

🇨🇦

Oshawa, Ontario, Canada

Dr. James Y. Cha

🇨🇦

Oshawa, Ontario, Canada

University Of Ottawa Heart Institute

🇨🇦

Ottawa, Ontario, Canada

Kawartha Cardiology Clinical Trials

🇨🇦

Peterborough, Ontario, Canada

Steeple Hill Medical Centre

🇨🇦

Pickering, Ontario, Canada

Scarborough Cardiology Research

🇨🇦

Scarborough, Ontario, Canada

Sarnia Institute Of Clinical Research

🇨🇦

Sarnia, Ontario, Canada

Scarborough General Hospital Cardiology Research Associates

🇨🇦

Scarborough, Ontario, Canada

Canadian Centre for Research on Diabetes

🇨🇦

Smith Falls, Ontario, Canada

Lake Shore Cardiology

🇨🇦

St. Catharines, Ontario, Canada

Sardar Medical Clinic

🇨🇦

St. Thomas, Ontario, Canada

G.S. Cardiac Lab Medicine Professional Corp

🇨🇦

Sudbury, Ontario, Canada

Dr. R. Labonte Professional Med Corp

🇨🇦

Sudbury, Ontario, Canada

Dr. G. Garrioch, Independent Practice

🇨🇦

Sudbury, Ontario, Canada

Dr. Laurence Gibbs Medicine Professional Corp.

🇨🇦

Thedford, Ontario, Canada

Tillsonburg Medical Centre

🇨🇦

Tillsonburg, Ontario, Canada

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

Mount Sinai Hospital

🇨🇦

Toronto, Ontario, Canada

St. Michael's Hospital

🇨🇦

Toronto, Ontario, Canada

Weston Road Medical Clinic

🇨🇦

Toronto, Ontario, Canada

Dr. Nwadiaro Medicine Professional Corp

🇨🇦

Windsor, Ontario, Canada

CHUM Hotel-Dieu

🇨🇦

Montreal, Quebec, Canada

Iucpq

🇨🇦

Quebec City, Quebec, Canada

ALPHA Recherche Clinique

🇨🇦

Québec, Quebec, Canada

Viacar Recherche Clinique

🇨🇦

St. Lambert, Quebec, Canada

Recherche Clinique Sigma, Inc.

🇨🇦

Quebec, Canada

Yolanda Sierra Quinones, MD

🇵🇷

Toa Baja, Puerto Rico

Santoscoy - Health Texas Research Institute

🇺🇸

San Antonio, Texas, United States

Element Research Group

🇺🇸

San Antonio, Texas, United States

Schnitzler Cardiovascular Consultants

🇺🇸

San Antonio, Texas, United States

San Antonio Endovascular & Heart Institute

🇺🇸

San Antonio, Texas, United States

Altru Health System Rehab Center

🇺🇸

Grand Forks, North Dakota, United States

Winnipeg Clinic

🇨🇦

Winnipeg, Manitoba, Canada

Stahl - Midwest Heart & Vascular Specialists

🇺🇸

Overland Park, Kansas, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

UCSF at Zuckerberg SF General Hospital

🇺🇸

San Francisco, California, United States

Clinical Research Center Meharry Medical College

🇺🇸

Nashville, Tennessee, United States

Utah Diabetes Center

🇺🇸

Salt Lake City, Utah, United States

Stern Cardiovascular Foundation, Inc.

🇺🇸

Germantown, Tennessee, United States

Arizona Arthritis & Rheumatology Research

🇺🇸

Phoenix, Arizona, United States

Sewa Ram Singal Medicine Professional Corporation

🇨🇦

Mississauga, Ontario, Canada

Humber River Hospital

🇨🇦

Toronto, Ontario, Canada

Toronto General Hospital

🇨🇦

Toronto, Ontario, Canada

Milliken Medical Centre

🇨🇦

Scarborough, Ontario, Canada

Source Unique Clinic

🇨🇦

Hawkesbury, Ontario, Canada

Dr. Nigel Jagan Medicine Professional Corporation

🇨🇦

Whitby, Ontario, Canada

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Vijay - Aurora Denver Cardiology

🇺🇸

Denver, Colorado, United States

John D. Dingell Veterans Affairs Medical Center

🇺🇸

Detroit, Michigan, United States

Trace Research Group at Wayne State University

🇺🇸

Detroit, Michigan, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Heart Consultants

🇺🇸

Omaha, Nebraska, United States

Alegent Creighton Health

🇺🇸

Omaha, Nebraska, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

COR Clinical Research, LLC

🇺🇸

Oklahoma City, Oklahoma, United States

Thadani - VA Medical Center Oklahoma City, OK

🇺🇸

Oklahoma City, Oklahoma, United States

Today Clinical Research

🇺🇸

Oklahoma City, Oklahoma, United States

Cardiovascular Health Clinic

🇺🇸

Oklahoma City, Oklahoma, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

Columbia St. Mary's

🇺🇸

Milwaukee, Wisconsin, United States

Aurora St. Luke's Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Jamaica Hospital Medical Center

🇺🇸

Jamaica, New York, United States

Eastside Clinical Research Associates

🇺🇸

Los Angeles, California, United States

Huntington Memorial Hospital

🇺🇸

Pasadena, California, United States

Southern Arizona VA Health Care System

🇺🇸

Tucson, Arizona, United States

North Ridge Heart Associates

🇺🇸

Boca Raton, Florida, United States

Heart Vascular of Northern Arizona

🇺🇸

Cottonwood, Arizona, United States

InterMed, PA

🇺🇸

Portland, Maine, United States

Scottsdale Medical Imaging

🇺🇸

Scottsdale, Arizona, United States

North Oaks Cardiology

🇺🇸

Hammond, Louisiana, United States

Maine Research Associates

🇺🇸

Auburn, Maine, United States

Pima Heart

🇺🇸

Tucson, Arizona, United States

GWU Medical Faculty Associatin, Inc.

🇺🇸

Washington, District of Columbia, United States

Cardiology Physicians/Red Clay Research

🇺🇸

Newark, Delaware, United States

CardioVascular Associates of Mesa

🇺🇸

Mesa, Arizona, United States

Ecogene-21

🇨🇦

Chicoutimi, Quebec, Canada

Q&T Research Chicoutimi

🇨🇦

Chicoutimi, Quebec, Canada

ViaCar Recherche Clinique Inc

🇨🇦

Saint-Lambert, Quebec, Canada

Cardiometabolic Research Center

🇵🇷

Ponce, Puerto Rico

Miguel Sosa-Padilla, MD

🇵🇷

San Juan, Puerto Rico

University Of California San Diego

🇺🇸

La Jolla, California, United States

University of MS Medical Center

🇺🇸

Jackson, Mississippi, United States

CardioVasc HR

🇨🇦

Saint-Jean-sur-Richelieu, Quebec, Canada

Jersey Shore University Medical Center

🇺🇸

Neptune, New Jersey, United States

Viacar Recherche Clinique Inc.

🇨🇦

Greenfield Park, Quebec, Canada

Joslin Diabetes Center

🇺🇸

Boston, Massachusetts, United States

San Juan Bautista School of Medicine

🇵🇷

Caguas, Puerto Rico

Gulfside Clinical Research, LLC

🇺🇸

Gulfport, Mississippi, United States

Veterans Affairs Medical Center Shreveport

🇺🇸

Shreveport, Louisiana, United States

The Valley Hospital

🇺🇸

Ridgewood, New Jersey, United States

Cardio Metabolic Institute

🇺🇸

Somerset, New Jersey, United States

Maine Centers for Healthcare

🇺🇸

Westbrook, Maine, United States

Great Falls Clinic Clinical Research Deptartment

🇺🇸

Great Falls, Montana, United States

Hopital Pierre-Le Gardeur

🇨🇦

Terrebonne, Quebec, Canada

Lahey Cardiology

🇺🇸

Nashua, New Hampshire, United States

VA Medical Center, White River Junction

🇺🇸

White River Junction, Vermont, United States

Instituto Sanacoop

🇵🇷

Bayamón, Puerto Rico

Norma S. Severino-Pacheco, MD

🇵🇷

Canovanas, Puerto Rico

Amistad Research Center, LLC

🇺🇸

Columbia, South Carolina, United States

Westwood Cardiology Associates

🇺🇸

Westwood, New Jersey, United States

Robley Rex VAMC

🇺🇸

Louisville, Kentucky, United States

Stoddard - University of Louisville

🇺🇸

Louisville, Kentucky, United States

Bays - L-MARC Research Center

🇺🇸

Louisville, Kentucky, United States

VA Medical Center Kansas City

🇺🇸

Kansas City, Missouri, United States

Orlando Healthy Heart Institute

🇺🇸

Orlando, Florida, United States

The Cardiac and Vascular Institute

🇺🇸

Gainesville, Florida, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

VA Pacific Islands Health Care System

🇺🇸

Honolulu, Hawaii, United States

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

Tulane University Office of Health Research

🇺🇸

New Orleans, Louisiana, United States

Presbyterian Heart Group

🇺🇸

Albuquerque, New Mexico, United States

Novel Research of New York, LLC

🇺🇸

Bronx, New York, United States

Avant Research Associates LLC

🇺🇸

Austin, Texas, United States

Texas Heart and Vascular Research, LLC

🇺🇸

Austin, Texas, United States

University Of Wisconsin

🇺🇸

Madison, Wisconsin, United States

Dean Foundation

🇺🇸

Madison, Wisconsin, United States

Professional Research Network of KS

🇺🇸

Wichita, Kansas, United States

Robert J. Dole VAMC

🇺🇸

Wichita, Kansas, United States

Dayton Heart Center

🇺🇸

Dayton, Ohio, United States

Dayton Veteran Affairs Medical Center

🇺🇸

Dayton, Ohio, United States

Metrolina Internal Medicine

🇺🇸

Charlotte, North Carolina, United States

Valley Clinical Trials, Inc.

🇺🇸

Northridge, California, United States

Endeavor Medical Research

🇺🇸

Alpena, Michigan, United States

John Gutleber Medical Research Office

🇺🇸

Homestead, Florida, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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