Clinical trial NCT02521168: Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia
Official title: Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative; Dysfunction Following Cardiac Surgery
Keywords: euthyroid sick syndrome
cardiopulmonary bypass
congenital heart disease
time to extubation
Lead sponsor: National Cardiovascular Center Harapan Kita Hospital Indonesia
Sponsor class: OTHER
Collaborators: name: CRDF Global
name: Osypka Germany
name: Dalim BioTech Co., Ltd.
First posted: 2015-08-13
Enrollment: 177
Sex: ALL
Minimum age (years): 1
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Eligibility criteria: 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

Primary outcomes:
measure: Intubation time
timeFrame: Until patients extubated after surgery in ICU OR died OR still intubated within 7 days
Secondary outcomes:
measure: Number of patients with low cardiac output syndrome
timeFrame: 6 hours, 12 hours, 18 hours, 24 hours, 48 hours post aortic cross clamp removal
measure: Drug adverse reaction
timeFrame: 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
Other outcomes:
measure: Inotropic and vasoactive-inotropic score
timeFrame: 1, 6, 12, 18, 24, 36, 48, 60 and 72 hours post cross clamp removal
measure: Diuresis
timeFrame: From day 1 until day 3 post surgery
measure: Fluid balance
timeFrame: From day 1until day 3 post surgery
measure: Lactate-pyruvate ratio
timeFrame: On induction of anaesthesia, 1 hour, 24 hours post cross clamp removal
measure: Ejection Fraction
timeFrame: Day 1, 2 and 3 post surgery
measure: Cardiac Index
timeFrame: Day 1, 2 and 3 post surgery
measure: Systemic Vascular Resistance Index
timeFrame: Day 1, 2 and 3 post surgery
measure: Pulse Pressure
timeFrame: Every hourly until 72 hours post surgery
measure: Number of patients with sepsis
timeFrame: since day 1 post surgery until patients discharge
Locations:
city: Jakarta
country: Indonesia
facility: Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita
state: DKI Jakarta
Study officials:
affiliation: National Cardiovascular Center Harapan Kita Jakarta
name: Eva M Marwali, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: