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NCT Number: NCT02521168

Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia

A condition of decreased serum T3 level in children after cardiac surgery using cardiopulmonary bypass has been commonly recognized as euthyroid sick syndrome (ESS). This syndrome has been closely associated with low cardiac output syndrome after heart surgery. The unique characteristics of pediatric patients with congenital heart disease (CHD) in Indonesia have caused ESS to arise in the population even before surgical managements. Thyroid hormones increase cardiac function, respiration and diuresis. Increased myocardial function occurred through the improvement of mitochondrial effectiveness as the body energy source by utilizing effective energy substrates, lactate and pyruvate. Prevention of decreased serum thyroid hormones level by T3 supplementation could be clinically beneficial. Intravenous T3 unit dose is very expensive and inapplicable for daily use. In adult studies, oral T3 was found to be effective for the prevention of decreased serum T3 levels; similar study on pediatric population, however, has not been elucidated.

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Key information

Conditions

Postoperative; Dysfunction Following Cardiac Surgery Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Endocrine System Diseases Euthyroid Sick Syndromes Heart Defects, Congenital Heart Diseases Thyroid Diseases

Age range

1 day–36 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita

Jakarta, DKI Jakarta, 11420, Indonesia

About this study

Methods:

The study was conducted at the cardiac paediatric cardiac intensive care unit of National Cardiovascular Center Harapan Kita. It was performed on paediatric congenital heart disease population who underwent open heart surgery with randomised, double-blind, controlled trial design. All patients with congenital heart disease, 3 years old or less, were included. Types of congenital heart disease suffered required subject to undergo surgery using cardiopulmonary bypass machine with Aristotle score of 6-9. Surgery was aimed for biventricular repair.

The sample size needed almost 200 patients with 50% is in the treatment group. This calculation was based on 90% of patients will be extubated and expected hazard ratio of corresponding treatment group is 1.7 with 5% alpha error and 20% beta error.

Patients were randomised using block randomisation procedure. The stratification factor will be age at the time of recruitment: < 6 weeks old, 6 weeks - 5 months old, > 5 months - 3 years old. Randomization will occur on the day of surgery.

The placebo - saccharum lactis - OR oral T3 (Tetronine, Dalim Biotech Korea) with the dose of 1 mcg per kg body weight were administered via nasogastric tube for every 6 hours starting from the time of anaesthesia induction until 11 doses in total (60 hours after the initial administration). Serial free T3 (FT3) and thyroid stimulating hormone (TSH) measurement were performed starting from the induction of anaesthesia until patient's discharge. Haemodynamics monitoring and echocardiography evaluation was conducted from day 1 to 3 after the surgery.

Statistical analysis:

Primary analysis will be performed using Cox Proportional Hazards for time to extubation result, including terms for stratification factors (age, Aristotle score and nutrition status). Patients will be included in analysis if they were randomised and received at least one dose of study drug according to the principal of Intention-to-Treat (ITT).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Children undergoing cardiopulmonary bypass
  • Age 36 months old or less
  • Aristotle score 6-9
  • Total correction or biventricular repair

Exclusion criteria

  • Single ventricle defects
  • Body weight less than 2 kg at the time of recruitment
  • Presentation with sepsis
  • Tachyarrhythmia or any other arrhythmia before surgery
  • Creatinine level of more than 2 mg/dl
  • Known thyroid disease
  • Known lung abnormalities (including infection) before surgery

Treatment and study plan

Oral triiodothyronine

Drug

Oral triiodothyronine is given peri-operatively through naso-gastric tube

Other names: Tetronine, Lyothyronine

Placebo

Drug

Placebo consist of saccharin lactis that has the same appearance as Tetronine

Other names: Saccharin lactis

Primary outcomes

  1. Intubation time

    Time frame: Until patients extubated after surgery in ICU OR died OR still intubated within 7 days

    All patients after undergoing congenital heart surgery will be supported by mechanical ventilation. Duration of this support since cross clamp off removal until after surgery will be assessed in the treatment and placebo group. Thyroid supplementation will increase the cardiac function and will make the patients extubated early than the patients without supplementation

Secondary outcomes

  1. Number of patients with low cardiac output syndrome

    Time frame: 6 hours, 12 hours, 18 hours, 24 hours, 48 hours post aortic cross clamp removal

    Identified patients with low cardiac output syndrome in which had clinical signs and symptoms of low cardiac output are found with without the increasing of arterial and venous gap and metabolic acidosis and this condition needs 100% of inotropic support or even more than that from the beginning of inotropic used, the use of new inotropic, mechanical support, or other manoeuvres in order to increase cardiac output (e.g pacemaker)

  2. Drug adverse reaction

    Time frame: Every hourly until 12 hours post cross clamp removal, every 3 hours until 24 hours, every 6 hours until 48 hours, every 12 hours until 72 hours post cross clamp removal, and until the patients discharge from hospital

    Heart rate to evaluate tachycardia, blood pressure for hypertension, heart rate for arrhythmia, body temperature for hyperthermia

Other outcomes

  1. Inotropic and vasoactive-inotropic score

    Time frame: 1, 6, 12, 18, 24, 36, 48, 60 and 72 hours post cross clamp removal

    The amount of inotropic drugs are calculated and reviewed serially since cross clamp removal until all drugs are stopped

  2. Diuresis

    Time frame: From day 1 until day 3 post surgery

    Amount of urine output per kg body weight per hour

  3. Fluid balance

    Time frame: From day 1until day 3 post surgery

    Difference between input and output of the fluid per kg body weight per day

  4. Lactate-pyruvate ratio

    Time frame: On induction of anaesthesia, 1 hour, 24 hours post cross clamp removal

    Lactate and pyruvate serum was obtained from central venous catheter in internal jugular vein with the distal tip catheter in the right atrium

  5. Ejection Fraction

    Time frame: Day 1, 2 and 3 post surgery

    Ejection Fraction is measured by Echocardiography

  6. Cardiac Index

    Time frame: Day 1, 2 and 3 post surgery

    Cardiac index is measured by Echocardiography

  7. Systemic Vascular Resistance Index

    Time frame: Day 1, 2 and 3 post surgery

    Systemic Vascular Resistance Index is measured by Echocardiography

  8. Pulse Pressure

    Time frame: Every hourly until 72 hours post surgery

    Difference between systolic and diastolic pressure

  9. Number of patients with sepsis

    Time frame: since day 1 post surgery until patients discharge

    Amount of patients diagnosis with sepsis based on Surviving Sepsis Campaign

Sponsors and collaborators

Lead sponsor

National Cardiovascular Center Harapan Kita Hospital Indonesia

Other

Collaborators

  • CRDF Global
  • Dalim BioTech Co., Ltd.
  • Osypka Germany

Registry information

Acronym: OTICC

Important dates

Study start
2013
Primary completion
2014
Study completion
2015
First posted
Aug 13, 2015
Registry last updated
Feb 17, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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