- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01780584
Can Oral T3 Normalize Thyroid Hormone Levels Following Cardiopulmonary Bypass in Children?
Oral Triiodothyronine Normalizes T3 Levels After Surgery For Pediatric Congenital Heart Disease
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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DKI Jakarta
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Jakarta, DKI Jakarta, Indonesia, 11420
- Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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)
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Comparison of different dosages of drug.
Low dose group oral T3 is 0.5 mcg/kg q24h
Other Names:
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 Names:
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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)
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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 Names:
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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)
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Comparison of different dosages of drugs.
Oral T3 high dose is 0.5 mcg/kg q12h
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Free T3 (FT3) Levels
Time Frame: during the first 36 hours after cross clamp removal
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Free T3 levels were measured up to 36 hours after cross-clamp removal
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during the first 36 hours after cross clamp removal
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Since the first dose of oral T3 until 7 days after surgery
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Postoperative Hospital Length of Stay
Time Frame: up to 3 month after surgery
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up to 3 month after surgery
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Postoperative Time to Extubation
Time Frame: up to 3 months after surgery
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Postoperative time to extubation is length of time on ventilator.
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up to 3 months after surgery
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Postoperative Length of Stay in Intensive Care Unit
Time Frame: up to 3 months after surgery
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up to 3 months after surgery
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Collaborators and Investigators
Investigators
- Principal Investigator: Eva M Marwali, MD, Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita Jakarta
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LB05.01/1.4/235/2010
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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