Postoperative; Dysfunction Following Cardiac SurgeryPhase 3OTICCNCT02521168
Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia
A Phase 3 study testing Oral triiodothyronine in people with Postoperative; Dysfunction Following Cardiac Surgery, run by National Cardiovascular Center Harapan Kita Hospital Indonesia at 1 site in Indonesia.
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. Read more about this study
- Who is it for?
- Ages 1 day to 36 months
- Conditions the study is for
- Postoperative; Dysfunction Following Cardiac Surgery
- What is being tested?
- Oral triiodothyronine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 177 participants
- Where
- 1 siteIndonesia
- Study dates
- Jul 2013to Jan 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 36 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children undergoing cardiopulmonary bypass
- Age 36 months old or less
- Aristotle score 6-9
- Total correction or biventricular repair
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Indonesia1 site
Pediatric Cardiac ICU National Cardiovascular Center Harapan Kita
Jakarta, DKI Jakarta, 11420
About this study
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.
Read the 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).
- Being tested
- Oral triiodothyronine, Placebo
- Keywords
- euthyroid sick syndrome, cardiopulmonary bypass, congenital heart disease, time to extubation
- Medical subject headings
- Euthyroid Sick Syndromes, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral triiodothyronineDrug
Also called Tetronine, Lyothyronine
Oral triiodothyronine is given peri-operatively through naso-gastric tube
PlaceboDrug
Also called Saccharin lactis
Placebo consist of saccharin lactis that has the same appearance as Tetronine
| Study group | Role | What they receive |
|---|---|---|
| Oral triiodothyronine | Experimental | Oral T3 (triiodothyronine) is given 1 mcg/kg every 6 hourly through naso-gastric tube since induction of anaesthesia for 60 hours Receives: Drug: Oral triiodothyronine |
| Placebo | Placebo comparator | Placebo (saccharin lactic) is given every 6 hourly through naso-gastric tube since induction of anaesthesia for 60 hours Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Until patients extubated after surgery in ICU OR died OR still intubated within 7 days
Secondary outcomes (2)
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)
Measured: 6 hours, 12 hours, 18 hours, 24 hours, 48 hours post aortic cross clamp removal
Drug adverse reaction
Heart rate to evaluate tachycardia, blood pressure for hypertension, heart rate for arrhythmia, body temperature for hyperthermia
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2015 (estimated)
- Study startJul 2013
- Primary completionOct 2014
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative; Dysfunction Following Cardiac SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 177 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cardiovascular Center Harapan Kita Hospital Indonesia
- Sponsor type
- University, hospital or other
- Collaborators
- CRDF Global, Osypka Germany, Dalim BioTech Co., Ltd.
- Responsible party
- Principal investigator, Eva M Marwali,MD, National Cardiovascular Center Harapan Kita Hospital Indonesia
- Investigators
- Eva M Marwali, MD, PhD, Principal investigator, National Cardiovascular Center Harapan Kita Jakarta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02521168
- Sponsor's protocol ID
- 164/H2.F1/ETIK/2013
- Acronym
- OTICC
- Status last verified
- Feb 2016
- First submitted
- 2 Aug 2015
- Last updated
- 17 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia
- ClinicalTrials.gov ID
- NCT02521168
- Acronym / sponsor ID
- OTICC / 164/H2.F1/ETIK/2013
- Keywords
- euthyroid sick syndrome, cardiopulmonary bypass, congenital heart disease, time to extubation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 177 participants (actual)
- Lead sponsor
- National Cardiovascular Center Harapan Kita Hospital IndonesiaUniversity, hospital or other
- Collaborators
- CRDF Global, Osypka Germany, Dalim BioTech Co., Ltd.
- Study start
- Jul 2013
- Primary completion
- Oct 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 13 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral triiodothyronine | Experimental | Drug: Oral triiodothyronineOral T3 (triiodothyronine) is given 1 mcg/kg every 6 hourly through naso-gastric tube since induction of anaesthesia for 60 hours |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (saccharin lactic) is given every 6 hourly through naso-gastric tube since induction of anaesthesia for 60 hours |
Who may qualify
- Ages
- 1 day to 36 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Children undergoing cardiopulmonary bypass
- Age 36 months old or less
- Aristotle score 6-9
- Total correction or biventricular repair
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral triiodothyronineAlso: Tetronine, LyothyronineOral triiodothyronine is given peri-operatively through naso-gastric tube | Drug | Oral triiodothyronine |
| PlaceboAlso: Saccharin lactisPlacebo consist of saccharin lactis that has the same appearance as Tetronine | Drug | Placebo |
Primary outcome
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
2 secondary outcomes
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva M Marwali, MD, PhD principal investigator
National Cardiovascular Center Harapan Kita Jakarta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oral triiodothyronine in people with Postoperative; Dysfunction Following Cardiac Surgery, run by National Cardiovascular Center Harapan Kita Hospital Indonesia at 1 site in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intubation time (time frame: Until patients extubated after surgery in ICU OR died OR still intubated within 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2016.