Folic Acid for Vascular Outcome Reduction in Transplantation Trial (FAVORIT)

General Description

The Folic Acid for Vascular Outcome Reduction in Transplantation Trial (FAVORIT) investigated if lowering homocysteine levels in renal transplant recipients with a multivitamin reduced the occurrence of cardiovascular disease (CVD) outcomes. In response to observational studies of patients with chronic kidney disease that suggested increased homocysteine is a risk factor for CVD, the study hypothesized that treatment with a high dose combination of folic acid, vitamin B6, and vitamin B12 would reduce the rate of pooled arteriosclerotic CVD outcomes among renal transplant recipients relative to treatment with an identical multivitamin containing no folic acid, and Estimated Average Requirement amounts of vitamin B6, vitamin B12. Stable kidney transplant recipients were randomized in a double-blind controlled trial to a multivitamin that included either a high dose or low-dose of folic acid, vitamin B6, and vitamin B12. Events such as recurrent or de novo arteriosclerotic CVD, renal graft failure, mortality, and creatinine-based estimates of renal function were monitored as outcome measures. The study found that treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not significantly reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. The trial was double-blind.

Additional stability testing was also conducted on a subset of serum and urine samples where fructosamine, glycolated albumin, and uromodulin levels were assessed after multiple freeze-thaw cycles.

Objectives

The FAVORIT study aimed to determine whether treatment with a high dose combination of folic acid, vitamin B12, and vitamin B6 reduces the risk of cardiovascular disease among clinically stable renal transplant recipients with elevated total homocysteine levels.

Outcome Measure

The primary outcome measure was recurrent or de novo arteriosclerotic cardiovascular disease, defined as the occurrence of non-fatal or fatal arteriosclerotic outcomes including coronary heart, cerebrovascular, and peripheral vascular disease events. Secondary outcome measures included renal graft failure, mortality, and creatinine-based estimates of renal function.

Criteria

Chronic renal transplant recipients (graft functioning for at least 6 months) aged 35 to 75 were enrolled in the study. Eligible participants were required to have Cockcroft-Gault serum creatinine based estimate of glomerular filtration rate (GFR) equal to or greater than 30 mL/min, and non-fasting plasma homocysteine ≥ 12 µmol/L in men and ≥ 11 µmol/L in women.

Outcome

The study found that treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. The stability testing conducted on urine and serum samples showed samples were stable through at least 3 freeze-thaw cycles.