drugset / Trial / NCT01594333
Cardiovascular Inflammation Reduction Trial
Phase 3
Completed
4786 enrolled
Brigham and Women's Hospital
National Heart, Lung, and Blood Institute (NHLBI) · collab
RandomizedParallel-groupTriple-blindTreatment
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).
Timeline
- Start
- 2013-04
- Primary completion
- 2019-04-15
- Completion
- 2019-10-30
Outcome
Results reported · no primary-endpoint met/missed verdict (typical of a dose-finding / safety study)
registry analysis (superiority test); Methotrexate vs Placebo; p = 0.91; Cox Proportional Hazard 1.01 (95% CI 0.82 to 1.25) NCT01594333 ↗
registry analysis (superiority test); Methotrexate vs Placebo; p = 0.67; Cox Proportional Hazard 0.96 (95% CI 0.79 to 1.16) NCT01594333 ↗
Publications
- Cui J, Ridker PM, Solomon DH. Blood pressure changes during methotrexate treatment: results from a randomized placebo-controlled trial among patients with cardiovascular risk. Rheumatology (Oxford). 2025 Jun 1;64(6):3917-3920. doi: 10.1093/rheumatology/keae604.
- Cui J, Di Martino V, Solomon DH. Longitudinal Follow-Up of Fibrosis-4 in Patients at Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease Receiving Low-Dose Methotrexate Treatment. Clin Gastroenterol Hepatol. 2024 Nov;22(11):2337-2339. doi: 10.1016/j.cgh.2024.03.035. Epub 2024 Apr 24.
- Cui J, Chasman DI, Raychaudhuri S, Xu C, Ridker PM, Solomon DH, Karlson EW. Genetics are not likely to offer clinically useful predictions for elevated liver enzyme levels in patients using low dose methotrexate. Semin Arthritis Rheum. 2022 Aug;55:152036. doi: 10.1016/j.semarthrit.2022.152036. Epub 2022 May 28.
- Reiss AB, Teboul I, Kasselman L, Ahmed S, Carsons SE, De Leon J. Methotrexate effects on adenosine receptor expression in peripheral monocytes of persons with type 2 diabetes and cardiovascular disease. J Investig Med. 2022 Aug;70(6):1433-1437. doi: 10.1136/jim-2022-002355. Epub 2022 May 23.
- Sparks JA, Vanni KMM, Sparks MA, Xu C, Santacroce LM, Glynn RJ, Ridker PM, Solomon DH. Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial. J Am Soc Nephrol. 2021 Dec 1;32(12):3197-3207. doi: 10.1681/ASN.2021050598. Epub 2021 Dec 1.
- Xu C, Selhub J, Jacques P, Paynter NP, MacFadyen JG, Glynn RJ, Ridker PM, Solomon DH. Adverse effects related to methotrexate polyglutamate levels: adjudicated results from the cardiovascular inflammation reduction trial. Rheumatology (Oxford). 2021 Jun 18;60(6):2963-2968. doi: 10.1093/rheumatology/keaa650.
- Sparks JA, Dellaripa PF, Glynn RJ, Paynter NP, Xu C, Ridker PM, Solomon DH. Pulmonary Adverse Events in Patients Receiving Low-Dose Methotrexate in the Randomized, Double-Blind, Placebo-Controlled Cardiovascular Inflammation Reduction Trial. Arthritis Rheumatol. 2020 Dec;72(12):2065-2071. doi: 10.1002/art.41452. Epub 2020 Oct 7.
- Ridker PM, MacFadyen JG, Glynn RJ, Bradwin G, Hasan AA, Rifai N. Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial. Eur Heart J. 2020 Aug 14;41(31):2952-2961. doi: 10.1093/eurheartj/ehaa160.
- Solomon DH, Glynn RJ, Karlson EW, Lu F, Corrigan C, Colls J, Xu C, MacFadyen J, Barbhaiya M, Berliner N, Dellaripa PF, Everett BM, Pradhan AD, Hammond SP, Murray M, Rao DA, Ritter SY, Rutherford A, Sparks JA, Stratton J, Suh DH, Tedeschi SK, Vanni KMM, Paynter NP, Ridker PM. Adverse Effects of Low-Dose Methotrexate: A Randomized Trial. Ann Intern Med. 2020 Mar 17;172(6):369-380. doi: 10.7326/M19-3369. Epub 2020 Feb 18.
- Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, Mam V, Hasan A, Rosenberg Y, Iturriaga E, Gupta M, Tsigoulis M, Verma S, Clearfield M, Libby P, Goldhaber SZ, Seagle R, Ofori C, Saklayen M, Butman S, Singh N, Le May M, Bertrand O, Johnston J, Paynter NP, Glynn RJ; CIRT Investigators. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019 Feb 21;380(8):752-762. doi: 10.1056/NEJMoa1809798. Epub 2018 Nov 10.
- Everett BM, Pradhan AD, Solomon DH, Paynter N, Macfadyen J, Zaharris E, Gupta M, Clearfield M, Libby P, Hasan AA, Glynn RJ, Ridker PM. Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis. Am Heart J. 2013 Aug;166(2):199-207.e15. doi: 10.1016/j.ahj.2013.03.018. Epub 2013 May 3.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Methotrexate | Small molecule | 15 mg | Oral |
| Subject | Methotrexate | Small molecule | 20 mg | Oral |