title: Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis.
abstract: BACKGROUND
  Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome.
  
  
  RESULTS
  The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7-22) for placebo and 20 hours (CI, 16-45) for Triostat and (hazard ratio, 0.60; P=0.0220).
  
  
  CONCLUSIONS
  T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417.
authors.affiliation: Seattle Children's Research Hospital and University of Washington, Seattle, WA 98101, USA. Michael.portman@seattlechildrens.org
authors.forename: Michael A
authors.initials: MA
authors.lastname: Portman
authors.forename: April
authors.initials: A
authors.lastname: Slee
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Olson
authors.forename: Gordon
authors.initials: G
authors.lastname: Cohen
authors.forename: Tom
authors.initials: T
authors.lastname: Karl
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tong
authors.forename: Laura
authors.initials: L
authors.lastname: Hastings
authors.forename: Hitendra
authors.initials: H
authors.lastname: Patel
authors.forename: Olaf
authors.initials: O
authors.lastname: Reinhartz
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Mott
authors.forename: Richard
authors.initials: R
authors.lastname: Mainwaring
authors.forename: Justin
authors.initials: J
authors.lastname: Linam
authors.forename: Sara
authors.initials: S
authors.lastname: Danzi
mesh_terms: D000367:Age Factors; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006330:Heart Defects, Congenital / Q000628:therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013997:Time Factors; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014284:Triiodothyronine