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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eva M Marwali,MD, National Cardiovascular Center Harapan Kita Hospital Indonesia
ClinicalTrials.gov Identifier:
NCT01780584
First received: January 28, 2013
Last updated: February 2, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Low T3 Syndrome
Drug: Oral T3 Low dose
Drug: Placebo
Drug: Oral T3 high dose
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Oral Triiodothyronine Normalizes T3 Levels After Surgery For Pediatric Congenital Heart Disease

Resource links provided by NLM:


Further study details as provided by National Cardiovascular Center Harapan Kita Hospital Indonesia:

Primary Outcome Measures:
  • Free T3 (FT3) Levels [ Time Frame: during the first 36 hours after cross clamp removal ] [ Designated as safety issue: Yes ]
    Free T3 levels were measured up to 36 hours after cross-clamp removal


Secondary Outcome Measures:
  • Number of Patients With Possible Side Effects of Thyroid Hormone Supplementation Particularly Suggesting Hyperthyroid Symptoms. [ Time Frame: Since the first dose of oral T3 until 7 days after surgery ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • Postoperative Time to Extubation [ Time Frame: up to 3 months after surgery ] [ Designated as safety issue: Yes ]
    Postoperative time to extubation is length of time on ventilator.

  • Postoperative Length of Stay in Intensive Care Unit [ Time Frame: up to 3 months after surgery ] [ Designated as safety issue: Yes ]
  • Postoperative Hospital Length of Stay [ Time Frame: up to 3 month after surgery ] [ Designated as safety issue: Yes ]

Enrollment: 45
Study Start Date: April 2010
Study Completion Date: October 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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)
Drug: Oral T3 Low dose
Comparison of different dosages of drug. Low dose group oral T3 is 0.5 mcg/kg q24h
Other Name: Tetronine
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
Other Name: Sacharin Lactis
Placebo Comparator: 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)
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
Other Name: Sacharin Lactis
Experimental: 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)
Drug: Oral T3 high dose
Comparison of different dosages of drugs. Oral T3 high dose is 0.5 mcg/kg q12h
Other Name: Tetronine

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.

  Eligibility

Ages Eligible for Study:   up to 24 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01780584

Locations
Indonesia
Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta
Jakarta, DKI Jakarta, Indonesia, 11420
Sponsors and Collaborators
National Cardiovascular Center Harapan Kita Hospital Indonesia
Investigators
Principal Investigator: Eva M Marwali, MD Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta
  More Information

Publications:
Responsible Party: Eva M Marwali,MD, Pediatric Cardiac Intensivist, National Cardiovascular Center Harapan Kita Hospital Indonesia
ClinicalTrials.gov Identifier: NCT01780584     History of Changes
Other Study ID Numbers: LB05.01/1.4/235/2010
Study First Received: January 28, 2013
Results First Received: February 2, 2013
Last Updated: February 2, 2013
Health Authority: Indonesia: Ethics Committee

Keywords provided by National Cardiovascular Center Harapan Kita Hospital Indonesia:
congenital heart surgery, thyroid hormones

Additional relevant MeSH terms:
Euthyroid Sick Syndromes
Thyroid Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 22, 2014