Abstract 2596: Triiodothyronine for Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) Study: Safety and Efficacy
The Triiodothyronine for Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) study is a multicenter, randomized, double-blinded, placebo-controlled clinical trial designed to determine safety and efficacy of triiodothyronine supplementation in children <2 years of age undergoing surgery for congenital heart disease.
METHODS The six-center study enrolled 195 patients; 99 (TR) randomized to multiple T3 (liothyronine) bolus over 12 hours during and after surgery and 96 to placebo (PL). Enrollment used a stratified design with central randomization to 9 diagnostic categories in high (HR) or low risk (LR) categories according to Aristotle Score. Primary endpoint was time to extubation (TE).
RESULTS Safety: The rates of all adverse events were nearly identical TR vs PL for Total, HR, and LR. The specific safety outcome, clinically important tachyarrhythmias, occurred in 9.4% PL, and 11.1% TR (p =0.69).
Efficacy. TR improved cardiac function assessed by shortening and ejection fractions, cardiac index, and/or myocardial performance index (LV TEI) by 24 hours in LR and HR patients (p< 0.05) and accelerated functional improvement compared to 6 hours. Function improved despite lower inotropic drug score. Kaplan-Meier analyses showed no significant differences with placebo for TE or ICU discharge in Total, HR or LR. However, pharmacokinetic analyses revealed that total plasma T3 (ng/dl) dropped to 57% baseline (161± 45(SD) to 92± 28) by 12 hrs in PL, but TR kept T3 greater than baseline. T3 levels at 6 hrs were significantly associated with TE. In PL, a 10 ng/dl decrease associated with a 21% decrease in the chance of extubation (p<0.001). In the TR, a 10 ng/dl increase in T3 associated with a 5% increase in chance of extubation (p=0.001).
CONCLUSIONS This large multicenter trial showed: 1) TRICC, as the largest study to date, demonstrates the feasibility of multi-center controlled clinical drug trials in children undergoing cardiac surgery. 2) Triiodothyronine (TR) is safe and does not increase risk for tachyarrhythmias in this susceptible population. 3) TR improves cardiac function without increasing use of inotropic agents. 4) TR removes the dramatic rapid declination of T3 levels, which poses substantial risk for delaying extubation.