Clinical Trials

The Cardiovascular Inflammation Reduction Trial (CIRT)

While inflammation plays a critical role in 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 funded by the National Heart Lung and Blood Institute (NHLBI) that will enroll 7,000 men and women from the United States and Canada.

Following a 5 to 6 week open-label run-in, eligible participants who have either suffered documented myocardial infarction in the past or have angiographically demonstrated multivessel coronary artery disease 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 per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis.

All study participants will additionally receive 1 mg oral folic acid to be taken daily six days per week.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.