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

Primary Purpose

Low T3 Syndrome

Status
Completed
Phase
Phase 2
Locations
Indonesia
Study Type
Interventional
Intervention
Oral T3 Low dose
Placebo
Oral T3 high dose
Sponsored by
National Cardiovascular Center Harapan Kita Hospital Indonesia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Low T3 Syndrome focused on measuring congenital heart surgery, thyroid hormones

Eligibility Criteria

1 Day - 24 Months (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Experimental

Arm Label

Oral T3 low dose & placebo

Placebo

Oral T3 high dose

Arm Description

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)

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)

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)

Outcomes

Primary Outcome Measures

Free T3 (FT3) Levels
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.
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.

Full Information

First Posted
January 28, 2013
Last Updated
February 2, 2013
Sponsor
National Cardiovascular Center Harapan Kita Hospital Indonesia
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1. Study Identification

Unique Protocol Identification Number
NCT01780584
Brief Title
Can Oral T3 Normalize Thyroid Hormone Levels Following Cardiopulmonary Bypass in Children?
Official Title
Oral Triiodothyronine Normalizes T3 Levels After Surgery For Pediatric Congenital Heart Disease
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cardiovascular Center Harapan Kita Hospital Indonesia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Low T3 Syndrome
Keywords
congenital heart surgery, thyroid hormones

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oral T3 low dose & placebo
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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)
Arm Title
Oral T3 high dose
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Oral T3 Low dose
Other Intervention Name(s)
Tetronine
Intervention Description
Comparison of different dosages of drug. Low dose group oral T3 is 0.5 mcg/kg q24h
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sacharin Lactis
Intervention Description
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
Intervention Name(s)
Oral T3 high dose
Other Intervention Name(s)
Tetronine
Intervention Description
Comparison of different dosages of drugs. Oral T3 high dose is 0.5 mcg/kg q12h
Primary Outcome Measure Information:
Title
Free T3 (FT3) Levels
Description
Free T3 levels were measured up to 36 hours after cross-clamp removal
Time Frame
during the first 36 hours after cross clamp removal
Secondary Outcome Measure Information:
Title
Number of Patients With Possible Side Effects of Thyroid Hormone Supplementation Particularly Suggesting Hyperthyroid Symptoms.
Description
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.
Time Frame
Since the first dose of oral T3 until 7 days after surgery
Other Pre-specified Outcome Measures:
Title
Postoperative Time to Extubation
Description
Postoperative time to extubation is length of time on ventilator.
Time Frame
up to 3 months after surgery
Title
Postoperative Length of Stay in Intensive Care Unit
Time Frame
up to 3 months after surgery
Title
Postoperative Hospital Length of Stay
Time Frame
up to 3 month after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
24 Months
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eva M Marwali, MD
Organizational Affiliation
Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta
City
Jakarta
State/Province
DKI Jakarta
ZIP/Postal Code
11420
Country
Indonesia

12. IPD Sharing Statement

Citations:
PubMed Identifier
20837917
Citation
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.
Results Reference
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Can Oral T3 Normalize Thyroid Hormone Levels Following Cardiopulmonary Bypass in Children?

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