Cardiovascular Inflammation Reduction Trial (CIRT)
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ClinicalTrials.gov Identifier: NCT01594333 |
Recruitment Status
:
Active, not recruiting
First Posted
: May 9, 2012
Last Update Posted
: April 5, 2018
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Cardiovascular Disease | Drug: Methotrexate Drug: Placebo | Phase 3 |
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 |

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)
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Placebo Comparator: Placebo |
Drug: Placebo
Tablet, Oral, weekly plus 1.0 mg folic acid 6 days/week
|
- 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.
- Rate of all-cause mortality [ Time Frame: Up to six years ]
- Rate of the primary endpoint plus coronary revascularization [ Time Frame: Up to six years ]
- Rate of hospitalization for congestive heart failure [ Time Frame: Up to six years ]
- Rate of primary endpoint plus all-cause mortality plus coronary revascularization plus congestive heart failure [ Time Frame: Up to six years ]
- Rate of new onset type 2 diabetes among those with metabolic syndrome but not diabetes at study entry [ Time Frame: Up to six years ]
- Rate of the primary endpoint plus unstable angina requiring unplanned coronary revascularization [ Time Frame: Up to six years ]
- Rate of coronary revascularization [ Time Frame: Up to six years ]
- Rate of peripheral artery disease [ Time Frame: Up to six years ]
- 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 ]
- Rate of clinically significant aortic stenosis [ Time Frame: Up to six years ]
- Rate of atrial fibrillation [ Time Frame: Up to six years ]

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

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

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 |