SAFETY OF INTRAVASCULAR TOCOPHEROL IN A RANDOMIZED DOUBLE BLIND TRIAL IN PREMATURE INFANTS

Abstract

We prospectively studied the potential side effects of parenteral vitamin E or tocopherol (T) while testing its effectiveness in preventing Retinopathy of Prematurity (ROP).287 infants <1.5 kg or <32 weeks were enrolled in a double blind, randomized trial of initial doses of 20 mg/Kg/day free T (or 0.4 cc/Kg of excipient placebo, [P]). Plasma levels were measured twice weekly and subsequent doses modified to a goal of 3.0-3.5 mg/dl. Undiluted drug was given over 5-15 min. via umbilical arterial or peripheral IV's. T or P was given PO when oral feeds were well established, and continued until the retinae reached maturity.Intravascular infusion of T or P caused no immediate or delayed reactions. The median plasma levels were 0.64 ± 0.63 mg/dl, M±SD in the P group, and 2.38 ± 0.82 mg/dl in the T group.Mortality, (20% P vs 21% T); CNS hemorrhage >grade I, (28% P vs 30% T); hepatomegaly of >2 cm (11% P vs 15% T); proven sepsis occurring after 48 hrs of age (7% P vs 6% T); and proven NEC (4% P vs 4% T) did not differ between the two groups. This sample size permitted 75-95% confidence for an increased incidence of any one side effect of 10 percentage points, alpha = 0.1.The early intravascular, followed by oral, use of tocopherol appears to be safe as used in this study, providing plasma levels are carefully monitored and kept below 3.5 mg/dl.