Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia

NCT ID: NCT02521168

Last Updated: 2016-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2015-01-31

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).

Conditions

Postoperative; Dysfunction Following Cardiac Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oral triiodothyronine

Oral T3 (triiodothyronine) is given 1 mcg/kg every 6 hourly through naso-gastric tube since induction of anaesthesia for 60 hours

Group Type: EXPERIMENTAL

Oral triiodothyronine

Intervention Type: DRUG

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

Placebo

Placebo (saccharin lactic) is given every 6 hourly through naso-gastric tube since induction of anaesthesia for 60 hours

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Oral triiodothyronine

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Tetronine; Lyothyronine; Saccharin lactis

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 36 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CRDF Global

OTHER

Sponsor Role: collaborator

Osypka Germany

UNKNOWN

Sponsor Role: collaborator

Dalim BioTech Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

National Cardiovascular Center Harapan Kita Hospital Indonesia

OTHER

Sponsor Role: lead

Responsible Party

Eva M Marwali,MD

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eva M Marwali, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Cardiovascular Center Harapan Kita Jakarta

Locations

Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita

Jakarta, DKI Jakarta, Indonesia

Countries

Indonesia

Other Identifiers

164/H2.F1/ETIK/2013

Identifier Type: -

Identifier Source: org_study_id