Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia
Condition: Postoperative; Dysfunction Following Cardiac Surgery
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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).
    

Intervention name(s): Oral triiodothyronine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral triiodothyronine is given peri-operatively through naso-gastric tube; Placebo consist of saccharin lactis that has the same appearance as Tetronine
Other intervention name(s): Tetronine; Lyothyronine; Saccharin lactis
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: euthyroid sick syndrome; cardiopulmonary bypass; congenital heart disease; time to extubation