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

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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

Tracking Information
First Submitted Date  ICMJE August 2, 2015
First Posted Date  ICMJE August 13, 2015
Last Update Posted Date February 17, 2016
Study Start Date  ICMJE July 2013
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2015)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2015)
  • 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)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 7, 2015)
  • 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
  • Diuresis [ Time Frame: From day 1 until day 3 post surgery ]
    Amount of urine output per kg body weight per hour
  • 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
  • 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
  • Ejection Fraction [ Time Frame: Day 1, 2 and 3 post surgery ]
    Ejection Fraction is measured by Echocardiography
  • Cardiac Index [ Time Frame: Day 1, 2 and 3 post surgery ]
    Cardiac index is measured by Echocardiography
  • Systemic Vascular Resistance Index [ Time Frame: Day 1, 2 and 3 post surgery ]
    Systemic Vascular Resistance Index is measured by Echocardiography
  • Pulse Pressure [ Time Frame: Every hourly until 72 hours post surgery ]
    Difference between systolic and diastolic pressure
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia
Official Title  ICMJE Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in 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.
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Postoperative; Dysfunction Following Cardiac Surgery
Intervention  ICMJE
  • Drug: Oral triiodothyronine
    Oral triiodothyronine is given peri-operatively through naso-gastric tube
    Other Names:
    • Tetronine
    • Lyothyronine
  • Drug: Placebo
    Placebo consist of saccharin lactis that has the same appearance as Tetronine
    Other Name: Saccharin lactis
Study Arms  ICMJE
  • 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
    Intervention: Drug: Oral triiodothyronine
  • Placebo Comparator: Placebo
    Placebo (saccharin lactic) is given every 6 hourly through naso-gastric tube since induction of anaesthesia for 60 hours
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 7, 2015)
177
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 36 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Indonesia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02521168
Other Study ID Numbers  ICMJE 164/H2.F1/ETIK/2013
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eva M Marwali,MD, National Cardiovascular Center Harapan Kita Hospital Indonesia
Study Sponsor  ICMJE National Cardiovascular Center Harapan Kita Hospital Indonesia
Collaborators  ICMJE
  • CRDF Global
  • Osypka Germany
  • Dalim BioTech Co., Ltd.
Investigators  ICMJE
Principal Investigator: Eva M Marwali, MD, PhD National Cardiovascular Center Harapan Kita Jakarta
PRS Account National Cardiovascular Center Harapan Kita Hospital Indonesia
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP