Can Oral T3 Normalize Thyroid Hormone Levels Following Cardiopulmonary Bypass in Children?
Condition: Low T3 Syndrome
MeSH terms: Euthyroid Sick Syndromes
Study type: Interventional
Phase: Phase 2

Summary: 
      Low triiodothyronine (T3) syndrome defines as decrease of T3 levels during critically ill.
      This decrease of T3 levels was observed after congenital heart surgery using cardiopulmonary
      bypass. Previous largest study,Triiodothyronine for Infants and Children Undergoing
      Cardiopulmonary bypass (TRICC) study showed T3 supplementation decreased time to extubation
      for infants less than 5 months undergoing cardiopulmonary bypass. Intravenous regiment was
      known effective in maintaining T3 levels during pediatric cardiac surgery. This drug
      preparation however is not commonly used in many countries due to the relatively high costs
      and/or the simple lack of availability. The use of oral T3 to treat postoperative low T3
      levels in pediatric patients has not been reported so far, although recent adult studies
      showed benefit in using oral T3 after cardiac surgery. The purpose of this study was to
      determine if oral T3 supplementation could prevent the decline of serum T3 in children less
      than 2 years of age undergoing congenital heart surgery using CPB.
    

Detailed description: 
      The Research Ethics Board at the National Cardiovascular Center Harapan Kita approved this
      study and written, informed consent was obtained from the parents or legal guardians before
      randomization. Randomization by block permutation was performed to determine treatment group
      assignment. Randomization occured on the day before surgery by a nurse investigator. A
      pharmacist who was not involved in the study prepared the study medication. Investigators and
      participants were blinded to the assigned group until after the end of the study.

      Thyroid hormonal levels were analyzed by standard 3rd generation thyrotropic-stimulating
      hormone (TSH), serum free T4 (FT4), free T3 (FT3), and total T3 (TT3) Micro particle Enzyme
      Immunoassays (Abbott Laboratories, Abbott Park, USA). The serum total T4 (TT4) assay used a
      Fluorescence Polarization Immunoassay (Abbott Laboratories, Abbott Park, USA). Hormone levels
      were measured on induction of anesthesia, before the study drug was given (T0) and at 1, 6,
      18, 36 and 72 hours after removal of the aortic-cross-clamp.

      Baseline clinical data collected included age, gender, birth weight, type of operation, and
      Aristotle score. Diagnosis and operative procedures were classified as high or low risk with
      an Aristotle score cut off of ≥ 9 as high risk. As modifying factors, we measured duration of
      surgery, cardiopulmonary bypass (CPB) time, cross-clamp time, ultrafiltration during CPB and
      degree of hypothermia during CPB, and the use of amiodarone. Non-pulsatile perfusion
      technique was used during CPB. Steroid (methyl prednisolone 35-50 mg/kg) was given before
      CPB. We used povidone-iodine for skin disinfection in all subjects. Although this study was
      not powered to detect clinical differences between the treatment groups, clinical outcome
      parameters were measured as a potential guide to subsequent adequately powered larger
      treatment studies. Serum lactate was measured at 1 hour, 4 hours and day 1 post surgery.
      Hemodynamic monitoring included heart rate, heart rhythm, and blood pressure which were
      recorded hourly for the first 6 hours then every 6 hours until 72 hours after surgery. Overt
      symptoms of hyperthyroidism were grounds for immediate removal of the subjects from the
      study. Time to extubation and length of stay in the intensive care unit and hospital were
      recorded.

      Statistical analysis and sample size: The primary efficacy analysis assessed the difference
      between the treatment (high-dose, low-dose) and control groups with regard to the effect of
      T3 supplementation on the measured TT3 and FT3 serum levels. We anticipated a difference of
      2.0 pg/ml in FT3 with a standard deviation of 0.8 pg/ml between groups. For a statistical
      power of 80% to identify a treatment effect and at a level of significance of 0.05 (
      2-sided), the target total sample size was 45 subjects, with 15 in each treatment group.
      Demographic data, safety and clinical outcomes were compared using the X2 test. Continuous
      variables for characteristics and outcomes were analyzed using one way ANOVA for data with
      normal distribution or the Kruskal Wallis test for not normally distributed data. Repeated
      measures ANOVA was used to analyze all thyroid hormone levels and clinical outcomes for those
      variables that were measured repeatedly over time. Paired Student's t-test for parametric or
      Wilcoxon signed rank test for non-parametric tests were used to evaluate the mean difference
      of hormone levels and clinical outcomes over time in each treatment group. Statistical
      significance was defined by p-values less than 0.05. Descriptive statistics are reported as
      mean ± standard error of the mean.
    

Intervention name(s): Oral T3 Low dose; Placebo; Oral T3 high dose
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Comparison of different dosages of drug. Low dose group oral T3 is 0.5 mcg/kg q24h; Comparison of different dosages of drug. In low dose group, placebo was given alternately with oral T3 every 12h with a total 3 doses for placebo and 3 doses for oral T3; Comparison of different dosages of drugs. Oral T3 high dose is 0.5 mcg/kg q12h
Other intervention name(s): Tetronine; Sacharin Lactis; Tetronine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: congenital heart surgery, thyroid hormones