Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia (OTICC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02521168
Recruitment Status : Completed
First Posted : August 13, 2015
Last Update Posted : February 17, 2016
Sponsor:
Collaborators:
CRDF Global
Osypka Germany
Dalim BioTech Co., Ltd.
Information provided by (Responsible Party):
Eva M Marwali,MD, National Cardiovascular Center Harapan Kita Hospital Indonesia

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.

Condition or disease Intervention/treatment Phase
Postoperative; Dysfunction Following Cardiac Surgery Drug: Oral triiodothyronine Drug: Placebo Phase 3

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 177 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia
Study Start Date : July 2013
Actual Primary Completion Date : October 2014
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Oral triiodothyronine
Oral T3 (triiodothyronine) is given 1 mcg/kg every 6 hourly through naso-gastric tube since induction of anaesthesia for 60 hours
Drug: Oral triiodothyronine
Oral triiodothyronine is given peri-operatively through naso-gastric tube
Other Names:
  • Tetronine
  • Lyothyronine

Placebo Comparator: Placebo
Placebo (saccharin lactic) is given every 6 hourly through naso-gastric tube since induction of anaesthesia for 60 hours
Drug: Placebo
Placebo consist of saccharin lactis that has the same appearance as Tetronine
Other Name: Saccharin lactis




Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 36 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02521168


Locations
Layout table for location information
Indonesia
Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita
Jakarta, DKI Jakarta, Indonesia, 11420
Sponsors and Collaborators
National Cardiovascular Center Harapan Kita Hospital Indonesia
CRDF Global
Osypka Germany
Dalim BioTech Co., Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Eva M Marwali, MD, PhD National Cardiovascular Center Harapan Kita Jakarta
Layout table for additonal information
Responsible Party: Eva M Marwali,MD, MD, PhD, National Cardiovascular Center Harapan Kita Hospital Indonesia
ClinicalTrials.gov Identifier: NCT02521168    
Other Study ID Numbers: 164/H2.F1/ETIK/2013
First Posted: August 13, 2015    Key Record Dates
Last Update Posted: February 17, 2016
Last Verified: February 2016
Keywords provided by Eva M Marwali,MD, National Cardiovascular Center Harapan Kita Hospital Indonesia:
euthyroid sick syndrome
cardiopulmonary bypass
congenital heart disease
time to extubation