Safety of Combined Therapy With Erythropoietin and Melatonin for Very Preterm Infants With Intraventricular Hemorrhage (SCEMPI)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Rate of SAE/DLT including death
研究概览
简要总结
Very preterm infants are prone to numerous medical complications with lifelong impact. Amongst the most serious neurologically are white matter injury (WMI), intraventricular hemorrhage (IVH) and the subsequent progression to posthemorrhagic hydrocephalus (PHH). Currently, the only treatment for PHH is surgery, most commonly with shunts that are prone to malfunction across the lifespan. Preclinical data show that melatonin (MLT) and erythropoietin (EPO), when administered in a sustained dosing regimen, may promote neuro-repair, including the progression from early postnatal IVH to subsequent PHH. The investigators will perform a Phase I, single institution, randomized, double-blind trial for very preterm infants with IVH and WMI to define a safe combination dose of MLT and EPO. A maximum of 60 very preterm neonates with IVH and/or moderate to severe WMI will be enrolled, treated through 33w6/7d, and followed to 37w6/7d. Neonates will be randomized 3:1 between MLT+EPO and placebo, with all receiving standard of care. The primary endpoint is a composite serious adverse event (SAE)/dose limiting toxicity (DLT). The investigators hypothesize that the MLT+EPO SAE/DLT rate will not be higher than the placebo rate. Secondary outcomes will be rate of co-morbidities of preterm birth. Exploratory data, collected to guide design of future clinical trials for efficacy, will include serial neuro-imaging metrics acquired from clinical images, serial neonatal neurodevelopmental examinations, serum and urine MLT and EPO levels, liquid and gut microbiome biomarkers. Successful implementation of this initial safety trial will provide essential data to guide the next stage of clinical trials to test if sustained MLT+EPO treatment can reduce neurological deficits, including the need for surgical intervention and the lifelong burden of shunted hydrocephalus.
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
- 12 Hours 至 2 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Neonatal intensive care unit (NICU) inpatients born at >22 and <32 weeks gestation (born after 22w-6/7 and before or on 31-6/7 week GA)
- •IVH or moderate/severe white matter injury within the first 21 days from birth
- •Infants born prior to 30 weeks GA may enroll until DOL
- •Infants born after 30 weeks may enroll until DOL
- •Treatment must be started by 33+
- •Approval of the primary neonatologist
- •Appropriate caregiver to provide informed consent
- •Is not known to meet or suspected of meeting any of the
排除标准
- •Exclusion Criteria:
- •Participation in another pharmacological intervention trial that involves multiple doses of a medication that may interact with EPO+MLT. Examples of exemptions would include single dose administration for pharmacokinetic studies of an antibiotic, a single or few doses of a new surfactant, or a single intervention to reduce pain.
- •Is on jet ventilator or has not been off jet ventilator for at least 72 hours
- •Has been diagnosed with or is suspected of having a congenital anomaly or genetic disorder associated with brain malformation or life expectancy <40 weeks post menstrual age (PMA). These include but are not limited to TORCH infections associated with radiographic evidence of substantial brain injury, trisomy 13, coarctation of the aorta, and severe liver failure. TORCH infections not associated with radiographic evidence of brain malformation or treatment for presumed TORCH infection are not exclusionary.
- •Is within 3 days of starting treatment for a severe clinical condition which is potentially associated with a life expectancy <3 days. These include but are not limited to disseminated intravascular coagulation (DIC)/severe hematologic crisis, severe sepsis, Hypoxic-ischemic encephalopathy (HIE), severe brain injury
- •Other clinical conditions including:
- •Hydrops fetalis Hypertension for age requiring sustained medication Polycythemia (hematocrit >65%)
- •- No caregiver to provide consent
- •The clinical condition of potential candidates will be monitored throughout the eligibility period to ensure the participant's continued candidacy for participating in the trial.
研究组 & 干预措施
MLT+EPO
Melatonin 3 mg/mL oral syringe enterally every evening. Dose will be divided in half and administered at evening cares.
High dose epoetin alfa epbx recombinant (1000 units/kg) syringe subcutaneously or intravenously every 48 hours for 10 doses.
Low dose epoetin alfa-epbx recombinant (400 units/kg) subcutaneously or intravenously three times weekly on Monday, Wednesday, and Friday until age 33-6/7wk.
干预措施: MLT+EPO (Combination Product)
Placebo
Placebo oral syringe enterally every evening.
Placebo syringe IV every 48 hours for 10 doses.
Placebo subcutaneously or intravenously three times weekly on Monday, Wednesday, and Friday until age 33-6/7wk.
干预措施: Placebo (Other)
结局指标
主要结局
Rate of SAE/DLT including death
时间窗: 4 weeks after the conclusion of treatment, up to 38 weeks gestational age
to test the hypothesis that rate of Serious Adverse Events (SAE)/dose limiting toxicity (DLT) with a cocktail of MLT and EPO in very preterm infants with severe intraventricular hemorrhage (sIVH) will have similar rate of SAE/DLT in subjects treated with placebo
次要结局
- Efficacy of EPO plus MLT as assessed by rate of preterm birth related co-morbidities(4 weeks after the conclusion of treatment, up to 38 weeks gestational age)