Oral Triiodothyronine for Infants Less Than 5 Months & Malnourished Children Undergoing Cardiopulmonary Bypass in Indonesia

NCT02222532 | Completed Phase 3 DMC

• 1 other identifier: GITX-14-60143-0
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 1

Brief Summary

Infants and children undergoing cardiac surgery require mechanical support for circulation called cardiopulmonary bypass. The artificial pump ensures that blood flow to the body is maintained during surgical procedure on the heart. However, the pump circulation disrupts regulation of thyroid hormone. This hormone is a critical regulator of heart and circulatory function. Deficiencies in thyroid hormone adversely affect recovery of the heart after cardiac surgery. A recent study by the principal investigator showed that supplementing patients younger than 5 months old shortened the time spent on the ventilator (breathing machine) after surgery. Populations undergoing heart surgery in developing countries such as Indonesia are different than those in the U.S. and other industrial nations. For many heart defects children undergo surgery at an older age. They are then sicker for longer periods, and are often malnourished. These older malnourished children have lower thyroid hormone levels even prior to surgery, and show dramatic further drops after surgery. Shortening time on the ventilator should improve their recovery, and also improve overall availability of resources in developing countries. The formulation of thyroid hormone provided in the U.S and given intravenous is relatively expensive. However, a much more inexpensive formulation is available in Indonesia, which can be given through a tube extending from the nose to the stomach. We propose testing this formulation made in Korea, known as Tetronine, in two vulnerable populations in Indonesia: children younger than 5 months of age, and those older than 5 months who are malnourished. All these patients will be undergoing cardiopulmonary bypass for congenital heart defects. This project will be an important collaboration between U.S and Indonesian investigators. If successful, it will have a general positive impact on care of the entire population of young children undergoing cardiac surgery in developing countries by reducing time on the ventilator and improving access to care.

Conditions

Postoperative; Dysfunction Following Cardiac Surgery

Keywords

tetronine; congenital heart disease; cardiopulmonary bypass; euthyroid sick syndrome

Outcome Measures

Primary Outcomes (1)

• Intubation time

  All patients after undergoing congenital heart surgery will be supported by mechanical ventilation. Duration of this support on mechanical ventilation after surgery will be assessed in the treatment group and placebo group. Thyroid supplementation will increase the cardiac function and will make the patients extubated early than the patients without supplementation.

  Up to 7 days post surgery

Secondary Outcomes (1)

• Inotropic score and vasoactive-inotropic score

  1, 6, 12, 18, 24, 36, 48, 60 and 72 hours post Cross clamp removal

Other Outcomes (6)

• Fluid balance

  Until day 3

• Hemodynamic parameter

  Every hourly until 12 hours post Cross clamp removal, every 3 hours until 24 hours, every 6 hours until 48 hours and every 12 hours until 72 hours post cross clamp removal,

• Low cardiac output syndrome

  6 hours, 12 hours, 18 hours, 24 hours and 48 hours post aortic cross clamp removal

Study Arms (2)

Tetronine

EXPERIMENTAL

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

Drug: Tetronine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Tetronine DRUG

Oral T3 was given 1 microgram/kgBW q6h since induction of anesthesia for 11 doses (for 60 hours)

Also known as: Oral Triidothyronine (T3)

Tetronine

Placebo DRUG

Placebo was sacharum lactis, given q6h since induction of anesthesia for 11 doses (for 60 hours)

Also known as: Saccharin Lactic

Placebo

Eligibility Criteria

• Age: 1 Day - 36 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children undergoing cardiopulmonary bypass
• Age 3 years old or less
• Aristotle score 6 and above
• Total correction or biventricular repair

You may not qualify if:

• 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 (incl. infection) before surgery.

Sponsors & Collaborators

• National Cardiovascular Center Harapan Kita Hospital Indonesia: lead
• CRDF Global: collaborator
• Osypka Germany: collaborator
• Dalim BioTech Co., Ltd.: collaborator

Study Sites (1)

Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita

Jakarta, DKI Jakarta, 11420, Indonesia

Location

Related Publications (3)

• Portman MA, Slee A, Olson AK, Cohen G, Karl T, Tong E, Hastings L, Patel H, Reinhartz O, Mott AR, Mainwaring R, Linam J, Danzi S; TRICC Investigators. Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis. Circulation. 2010 Sep 14;122(11 Suppl):S224-33. doi: 10.1161/CIRCULATIONAHA.109.926394.

  PMID: 20837917 BACKGROUND

• Marwali EM, Boom CE, Sakidjan I, Santoso A, Fakhri D, Kartini A, Kekalih A, Schwartz SM, Haas NA. Oral triiodothyronine normalizes triiodothyronine levels after surgery for pediatric congenital heart disease*. Pediatr Crit Care Med. 2013 Sep;14(7):701-8. doi: 10.1097/PCC.0b013e3182917f87.

  PMID: 23842591 BACKGROUND

• Marwali EM, Lopolisa A, Sani AA, Rayhan M, Roebiono PS, Fakhri D, Haas NA, Slee A, Portman MA. Indonesian Study: Triiodothyronine for Infants Less than 5 Months Undergoing Cardiopulmonary Bypass. Pediatr Cardiol. 2022 Apr;43(4):726-734. doi: 10.1007/s00246-021-02779-8. Epub 2021 Dec 1.

  PMID: 34851445 DERIVED

MeSH Terms

Conditions

Heart Defects, Congenital; Euthyroid Sick Syndromes

Interventions

Triiodothyronine

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyronines; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thyroxine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Eva M Marwali, MD

  National Cardiovascular Center Harapan Kita Jakarta

  PRINCIPAL INVESTIGATOR

• Michael A Portman, MD

  University of Washington

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 18, 2014
• First Posted: August 21, 2014
• Study Start: June 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 17, 2016

Record last verified: 2016-02

Locations

ID (1)