Low T3 Syndrome Clinical Trial
Official title:
Oral Triiodothyronine Normalizes T3 Levels After Surgery For Pediatric Congenital Heart Disease
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.
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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
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