Rationale and design of the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial
Background
Patients with chronic kidney disease, including kidney transplant recipients, are at high risk for cardiovascular disease (CVD). In addition to the constellation of traditional CVD risk factors in chronic kidney disease, elevated total homocysteine (tHcy) is notably more prevalent among the general population. The Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial is designed to evaluate whether lowering tHcy using vitamin supplementation reduces CVD events in renal transplant recipients.
Methods
FAVORIT is a multicenter double-blind randomized controlled clinical trial. Participants are clinically stable renal transplant recipients who are 6 months or longer posttransplant with elevated tHcy. Patients are randomized to a multivitamin that includes either a high-dose or low-dose of folic acid (5 or 0 mg), vitamin B6 (50 or 1.4 mg), and vitamin B12 (1000 or 2 μg). The primary end point is a composite of incident or recurrent CVD outcomes, that is, coronary heart, cerebrovascular, or abdominal aortic/lower extremity arterial events. A sample size of 4000 is estimated to provide 87% power to detect a 20% treatment effect. Recruitment is expected to continue until July 2006, with follow-up through June 2010.
Results
From August 2002 through December 2004, 2234 of the target 4000 patients were enrolled. In accordance with trial design, mean (SD) screening tHcy was elevated (17.4 ± 6.2 μmol/L), and mean (SD) estimated creatinine clearance was consistent with stable renal function (58.0 ± 18.6 mL/min). Evaluating baseline results to date, 42% of the randomized participants had a history of diabetes mellitus, and 21% had prevalent CVD.
Conclusions
The FAVORIT trial is designed with sufficient power and follow-up time to detect a clinically relevant change in CVD risk between renal transplant recipients receiving a high or low tHcy-lowering folic acid multivitamin. Preliminary screening and baseline data support the trial's objectives.
A list of the FAVORIT Investigators can be found in Appendix A. Members of the Data and Safety Monitoring Board are listed in Appendix B.
This research was supported by cooperative agreement U01 DK61700-01 from the National Institute of Diabetes and Digestive and Kidney Diseases and additional financial support from the Office of Dietary Supplements, National Institutes of Health, Department of Health and Human Services. Vitamins were provided by Pamlab, L.L.C.
PII: S0002-8703(06)00229-8
doi:10.1016/j.ahj.2006.03.004
© 2006 Mosby, Inc. All rights reserved.
