N/A
N=50
Coronary Flow Reserve to Assess Cardiovascular Inflammation (CIRT-CFR)
Coronary Heart Disease · Metabolic Syndrome · Diabetes Mellitus
Bottom Line
View on ClinicalTrials.gov: NCT02786134 ↗Enrolled (actual)
50
Serious AEs
0.0%
Results posted
Jan 2021
Primary outcome: Primary: Change in Global Myocardial Blood Flow in Response to Vasodilator — 0.05; -0.145 percentage change in CFR
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- PET scan (Radiation); Echocardiogram (Radiation)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Brigham and Women's Hospital
- Primary completion
- Oct 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Global Myocardial Blood Flow in Response to Vasodilator |
0.05; -0.145 | — |
Summary
Coronary flow reserve (CFR, calculated as the ratio of hyperemic over rest myocardial blood flow) is emerging as a powerful quantitative prognostic imaging marker of clinical cardiovascular risk. CFR provides a robust and reproducible clinical measure of the integrated hemodynamic effects of epicardial coronary artery disease (CAD), diffuse atherosclerosis, and microvascular dysfunction on myocardial tissue perfusion. Inflammation is a key mediator of this constellation of abnormalities, affecting the entire coronary vasculature, but no clinical trial to date has shown that directly reducing inflammation lowers cardiovascular event rates. As such, the recently launched Cardiovascular Inflammation Reduction Trial (CIRT) provides a unique opportunity for mechanistic investigation of the impact of anti-inflammatory therapy on changes in CFR as a reflection of coronary vascular dysfunction, which may precede clinical outcomes, particularly in patients at high-risk of events. The investigators are ideally positioned to examine the impact of inflammation on CFR, having extensive experience in both the quantitation of CFR using clinically-integrated dynamic positron emission tomography (PET) and the ability to assess its association with cardiovascular outcomes. The central hypothesis of this ancillary proposal, CIRT-CFR, is that reducing systemic inflammation using low-dose methotrexate (LDM) will, compared to placebo, quantitatively improve myocardial blood flow and coronary flow reserve as measured by PET over one year, in stable CAD patients with type 2 diabetes or metabolic syndrome enrolled in CIRT. In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular deformation and function and, ultimately, symptoms and prognosis.
Eligibility Criteria
Inclusion Criteria
- Age ≥18 years at screening;
- Documented past history of MI OR past evidence of multivessel CAD by angiography, completed any planned coronary revascularization associated with a qualifying event at least 60 days prior to enrollment, and clinically stable for ≥60 days prior to enrollment; qualifying prior MI must be documented either by hospital records, evidence on current ECG of Q waves in 2 contiguous leads, and/or an imaging test demonstrating wall motion abnormality or scar; qualifying evidence of multivessel CAD by angiography must be documented by CAD in at least two major epicardial vessels defined either as the presence of a stent, a coronary artery bypass graft, or an angiographic lesion of 60% or greater (left main CAD 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);
- History of type 2 DM or metabolic syndrome (meeting 2004 AHA/NHLBI definition*) at time of study enrollment; *includes any 3 of the following 5 diagnostic criteria: waist circumference ≥ 102 cm in men or 88 cm in women; triglycerides ≥ 150 mg/dl or on drug treatment for elevated triglycerides; high-density lipoprotein cholesterol (HDL-C) 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 (see Exclusionary Medication List in Manual of Operations). 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.
Data sourced from ClinicalTrials.gov (NCT02786134). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.