Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia

Postoperative; Dysfunction Following Cardiac Surgery Clinical Trial

— OTICC  

Official title:

Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02521168
• Other study ID #: 164/H2.F1/ETIK/2013
• Status: Completed
• Phase: Phase 3
• First received: August 2, 2015
• Last updated: February 16, 2016
• Start date: July 2013
• Est. completion date: January 2015

Study information

• Verified date: February 2016
• Source: National Cardiovascular Center Harapan Kita Hospital Indonesia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Indonesia: National Agency of Drug and Food Control
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: January 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 36 Months

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Postoperative; Dysfunction Following Cardiac Surgery

Intervention

Drug:
• Oral triiodothyronine
Oral triiodothyronine is given peri-operatively through naso-gastric tube
• Placebo
Placebo consist of saccharin lactis that has the same appearance as Tetronine

Locations

Country	Name	City	State
Indonesia	Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita	Jakarta	DKI Jakarta

Sponsors (4)

Lead Sponsor	Collaborator
National Cardiovascular Center Harapan Kita Hospital Indonesia	CRDF Global, Dalim BioTech Co., Ltd., Osypka Germany

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Inotropic and vasoactive-inotropic score	The amount of inotropic drugs are calculated and reviewed serially since cross clamp removal until all drugs are stopped	1, 6, 12, 18, 24, 36, 48, 60 and 72 hours post cross clamp removal	No
Other	Diuresis	Amount of urine output per kg body weight per hour	From day 1 until day 3 post surgery	No
Other	Fluid balance	Difference between input and output of the fluid per kg body weight per day	From day 1until day 3 post surgery	No
Other	Lactate-pyruvate ratio	Lactate and pyruvate serum was obtained from central venous catheter in internal jugular vein with the distal tip catheter in the right atrium	On induction of anaesthesia, 1 hour, 24 hours post cross clamp removal	No
Other	Ejection Fraction	Ejection Fraction is measured by Echocardiography	Day 1, 2 and 3 post surgery	No
Other	Cardiac Index	Cardiac index is measured by Echocardiography	Day 1, 2 and 3 post surgery	No
Other	Systemic Vascular Resistance Index	Systemic Vascular Resistance Index is measured by Echocardiography	Day 1, 2 and 3 post surgery	No
Other	Pulse Pressure	Difference between systolic and diastolic pressure	Every hourly until 72 hours post surgery	No
Other	Number of patients with sepsis	Amount of patients diagnosis with sepsis based on Surviving Sepsis Campaign	since day 1 post surgery until patients discharge	No
Primary	Intubation time	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	Until patients extubated after surgery in ICU OR died OR still intubated within 7 days	Yes
Secondary	Number of patients with low cardiac output syndrome	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)	6 hours, 12 hours, 18 hours, 24 hours, 48 hours post aortic cross clamp removal	No
Secondary	Drug adverse reaction	Heart rate to evaluate tachycardia, blood pressure for hypertension, heart rate for arrhythmia, body temperature for hyperthermia	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	Yes