Can Oral T3 Normalize Thyroid Hormone Levels Following Cardiopulmonary Bypass in Children?

NCT ID: NCT01780584

Last Updated: 2013-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2010-10-31

Brief 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.

Conditions

Low T3 Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Oral T3 low dose & placebo

Oral T3 low dose administer through nasogastric tube 0.5 mcg/kg (max 10 mcg) starting on induction of anesthesia and then every 24 hours alternating with placebo, which was given 12 hours after the first dose of oral T3 and then every 24 hours until 60 hours post anesthesia induction (3 doses oral T3, 3 doses placebo)

Group Type: ACTIVE_COMPARATOR

Oral T3 Low dose

Intervention Type: DRUG

Comparison of different dosages of drug. Low dose group oral T3 is 0.5 mcg/kg q24h

Placebo

Intervention Type: DRUG

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

Placebo

Placebo (saccharin lactic) administer through nasogastric tube, given starting on induction of anesthesia and then every 12 hours until 60 hours post-anesthesia induction (6 doses total)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Oral T3 high dose

Oral T3 high dose administer through nasogastric tube 0.5 mcg/kg (max 10 mcg) q12h starting on induction of anesthesia until 60 hours post-anesthesia (6 doses oral T3)

Group Type: EXPERIMENTAL

Oral T3 high dose

Intervention Type: DRUG

Comparison of different dosages of drugs. Oral T3 high dose is 0.5 mcg/kg q12h

Interventions

Oral T3 Low dose

Comparison of different dosages of drug. Low dose group oral T3 is 0.5 mcg/kg q24h

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Oral T3 high dose

Comparison of different dosages of drugs. Oral T3 high dose is 0.5 mcg/kg q12h

Intervention Type: DRUG

Other Intervention Names

Tetronine; Sacharin Lactis; Tetronine

Eligibility Criteria

Inclusion Criteria

• Patients between 0-2 years of age
• Aristotle score of 6 and above
• underwent cardiac surgery using cardiopulmonary bypass

Exclusion Criteria

• birth weight less than 2 kg for neonates
• preoperative tachyarrhythmia or need for anti arrhythmic treatment
• clinical sepsis confirmed by culture
• preoperative renal insufficiency
• known thyroid and metabolic disorder
• any contraindication for oral T3 administration

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cardiovascular Center Harapan Kita Hospital Indonesia

OTHER

Sponsor Role: lead

Responsible Party

Eva M Marwali,MD

Pediatric Cardiac Intensivist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eva M Marwali, MD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta

Locations

Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta

Jakarta, DKI Jakarta, Indonesia

Countries

Indonesia

References

Portman MA, Slee A, Olson AK, Cohen G, Karl T, Tong E, Hastings L, Patel H, Reinhartz O, Mott AR, Mainwaring R, Linam J, Danzi S; TRICC Investigators. Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis. Circulation. 2010 Sep 14;122(11 Suppl):S224-33. doi: 10.1161/CIRCULATIONAHA.109.926394.

Reference Type: RESULT

PMID: 20837917 (View on PubMed)

Other Identifiers

LB05.01/1.4/235/2010

Identifier Type: -

Identifier Source: org_study_id