Prospective, Randomized, Double-blind, Cohort Study of Hydrocortisone vs Placebo in Systemic Low Blood Pressure During Hypothermia Treatment in Asphyxiated Newborns
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Compare mean arterial blood pressure (MAP) change in the patients receiving hydrocortisone vs placebo
研究概览
简要总结
This is a prospective, randomized, double-blind, placebo controlled, single center study to compare low dose hydrocortisone vs placebo in systemic low blood pressure during hypothermia treatment in asphyxiated newborns. Patients will be allocated to one of the treatment arms (hydrocortisone or placebo) while receiving conventional inotropic therapy as needed.
The hypothesis is that cooled asphyxiated neonates develop relative adrenal insufficiency that may contribute to hypotension and lower efficacy of inotropic therapy in this patient population. Thus, the investigators are planning to measure initial serum cortisol levels and investigate the cardiovascular effects of low dose hydrocortisone supplementation besides conventional inotropic therapy in a placebo-controlled fashion.
详细描述
Hypothesis:
The researchers hypothesized that asphyxiated neonates undergoing therapeutic hypothermia develop relative adrenal insufficiency that contributes to "late onset" (>24 hours after birth) hypotension resistant to optimized pharmacological support.
Thus, the investigators are planning to measure initial serum cortisol levels and investigate the cardiovascular effects of low dose hydrocortisone supplementation.
Specific aims:
- To study initial serum cortisol levels in asphyxiated newborns undergoing therapeutic hypothermia with late onset hypotension.
- To demonstrate that in asphyxiated newborns undergoing therapeutic hypothermia and presenting with systemic hypotension resistant to optimized pharmacological support, low dose hydrocortisone supplementation restores normal blood pressure when compared to placebo.
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
- — 至 72 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The infant will be assessed sequentially by criteria A, B and C, as described by the TOBY trial and listed below, to be eligible for hypothermia treatment.
- •A. Infants ≥ 36 completed weeks of gestation admitted to the NICU with at least one of the following:
- •Apgar score of ≤ 5 at 10 minutes after birth
- •Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth
- •Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord, arterial or capillary pH < 7.00)
- •Base Deficit ≥ 16 mmol/L in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth
- •B. Moderate to severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) AND at least one of the following:
- •hypotonia
- •abnormal reflexes including oculomotor or pupillary abnormalities
- •absent or weak suck
- •clinical seizures
- •C. At least 30 minutes duration of aEEG recording that shows abnormal background aEEG activity or seizures. There must be one of the following:
- •normal background with some seizure activity
- •moderately abnormal activity
- •suppressed activity
- •continuous seizure activity
- •Invasive arterial blood pressure measurement: umbilical arterial catheter or peripheral arterial catheter to measure invasively the arterial blood pressure.
- •During hypothermia treatment low blood pressure was detected and treated with the following:
- •fluid therapy: 10-20 ml/kg isotonic NaCl if hypotension is still present
- •inotropic therapy: dopamine in parallel with study intervention
- •A written informed consent has been obtained from a parent of each infant after explanation of the study.
排除标准
- •Signed informed consent is unavailable.
- •Infants who are expected to be > 6 hours of age (not suitable for cooling).
- •Congenital abnormalities, cardiac anomalies, meconium aspiration syndrome.
- •Low blood pressure coincides with high heart rate (>120/min) in cooled infants, suggesting hypovolaemia.
- •Haematocrit level < 35%.
- •Need for combined, ≥2 types of inotropic therapy.
研究组 & 干预措施
Hydrocortisone
Hydrocortisone is the pharmaceutical term for cortisol, the principal glucocorticoid secreted by the adrenal gland
干预措施: Hydrocortisone (Drug)
Placebo
Isotonic sodium chloride is an aqueous solution of 0.9 percent sodium chloride which is isotonic with the blood and tissue fluid
干预措施: Placebo (Drug)
结局指标
主要结局
Compare mean arterial blood pressure (MAP) change in the patients receiving hydrocortisone vs placebo
时间窗: 2 hours
Circulatory stability as measured by an increased MAP (5 mmHg) within two hours after drug administration
次要结局
- Length of dopamine treatment in the patients receiving hydrocortisone vs placebo(72 hours)
- Frequency of initially low serum cortisol in hypotensive asphyxiated newborns undergoing therapeutic hypothermia(before hydrocortisone administration within max. 72 hours)
- Cumulative dopamine dose in the patients receiving hydrocortisone vs placebo(72 hours)
- Change in hourly diuresis in the patients receiving hydrocortisone vs placebo(72 hours)
- Change in the echocardiography parameters (fractional shortening and cardiac output) in the patients receiving hydrocortisone vs placebo(72 hours)
- Long term neurodevelopmental outcome in the patients receiving hydrocortisone vs placebo(18-22 month)
研究者
Agnes Jermendy MD PhD MPH
assistant lecturer
Semmelweis University