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

Low T3 Syndrome Clinical Trial

Official title:

Oral Triiodothyronine Normalizes T3 Levels After Surgery For Pediatric Congenital Heart Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01780584
• Other study ID #: LB05.01/1.4/235/2010
• Status: Completed
• Phase: Phase 2
• First received: January 28, 2013
• Last updated: February 2, 2013
• Start date: April 2010
• Est. completion date: October 2010

Study information

• Verified date: February 2013
• Source: National Cardiovascular Center Harapan Kita Hospital Indonesia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Indonesia: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: October 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 24 Months

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Low T3 Syndrome

Intervention

Drug:
• Oral T3 Low dose
Comparison of different dosages of drug. Low dose group oral T3 is 0.5 mcg/kg q24h
• 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
• Oral T3 high dose
Comparison of different dosages of drugs. Oral T3 high dose is 0.5 mcg/kg q12h

Locations

Country	Name	City	State
Indonesia	Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta	Jakarta	DKI Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
National Cardiovascular Center Harapan Kita Hospital Indonesia

Country where clinical trial is conducted

Indonesia, 

References & Publications (1)

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 mu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Postoperative Time to Extubation	Postoperative time to extubation is length of time on ventilator.	up to 3 months after surgery	Yes
Other	Postoperative Length of Stay in Intensive Care Unit		up to 3 months after surgery	Yes
Other	Postoperative Hospital Length of Stay		up to 3 month after surgery	Yes
Primary	Free T3 (FT3) Levels	Free T3 levels were measured up to 36 hours after cross-clamp removal	during the first 36 hours after cross clamp removal	Yes
Secondary	Number of Patients With Possible Side Effects of Thyroid Hormone Supplementation Particularly Suggesting Hyperthyroid Symptoms.	Specific symptoms of hyperthyroidism included cardiac dysrhythmia requiring medical or electrical treatment, hypertension (mean systolic or diastolic blood pressure more than 2 standard deviation above normal for age) and hyperthermia (>37.5 degree Celsius). One patient in low dose group had hypertension directly after surgery due to unrecognized coarctation of the aorta and this patient was withdrawal from the protocol.	Since the first dose of oral T3 until 7 days after surgery	Yes