Tetronine (Sodium Liothyronine) for Infants & Children Undergoing Cardiopulmonary Bypass in a Middle Income Nation (OTICC Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 224
- 试验地点
- 1
- 主要终点
- Intubation time
研究概览
简要总结
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.
详细描述
Methods
Study Overview and Objectives We will perform a randomized double blinded placebo controlled trial in Indonesian children under 3 years of age, who are undergoing cardiopulmonary bypass procedures for correction or palliation of congenital heart disease. The study is approved by the Ethic Committee for Medical Research National Cardiovascular Center Harapan Kita (NCCHK). Age 3 years was chosen as the cutoff, as the population < 3 years has the highest mortality rate in Indonesia. Also, this cutoff reduces age-based population heterogeneity, which could confound the analyses. We will study two independent vulnerable cohorts within this population as previously noted.
- Age < 5 months
- Age > 5 months and < 3 years with moderate to severe malnutrition
Moderate to severe malnutrition is defined as weight more than 15% below the predicted value for height. The predicted value will be determined using WHO clinical growth charts based on the patient gender and baseline length and weight measurements. There is no overlap in study cohorts (patients ≤ 5 months of age and patients > 5 months of age with moderate to severe malnutrition form mutually exclusive groups). Thus, this study can be viewed as two separate, independent trials, each with an overall type I error rate of 0.05 (2-sided). The primary endpoint within each study cohort is a comparison of time to the first of death, 7 days, or extubation based on the log-rank statistic from separate Cox Proportional Hazards Models. These models will include Aristotle Score and other baseline covariates imbalanced across treatment groups. Patients will be monitored until the first of death, withdrawal of consent, or hospital discharge.
Safety Endpoints
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 36 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children undergoing cardiopulmonary bypass
- •Age 3 years old or less
- •Aristotle score 6 and above
- •Total correction or biventricular repair
排除标准
- •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.
研究组 & 干预措施
Tetronine
Oral T3 (Tetronine) is given 1 mcg/kg every 6 hourly through naso-gastric tube since induction of anesthesia for 60 hours
干预措施: Tetronine (Drug)
Placebo
Placebo (saccharin lactic) is given every 6 hourly through naso-gastric tube since induction of anesthesia for 60 hours
干预措施: Placebo (Drug)
结局指标
主要结局
Intubation time
时间窗: Up to 7 days post surgery
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.
次要结局
- Inotropic score and vasoactive-inotropic score(1, 6, 12, 18, 24, 36, 48, 60 and 72 hours post Cross clamp removal)
研究者
Eva M Marwali,MD
MD
National Cardiovascular Center Harapan Kita Hospital Indonesia