RIC-NEC Phase II Feasibility Randomized Controlled Trial: Remote Ischemic Conditioning in Necrotizing Enterocolitis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 78
- 试验地点
- 7
- 主要终点
- The proportion (% total) of randomized patients that receive allocated intervention.
研究概览
简要总结
Necrotizing enterocolitis (NEC) is a serious intestinal disease of preterm and term neonates which remains a major cause of intestinal failure, and an unsolved clinical challenge in pediatrics. While overall mortality of preterm infants continues to decrease due to improvements in general neonatal care, mortality caused by NEC remains high (up to 30-50%) and survivors suffer from reduced quality of life, and long-term disabilities such as debilitating complications of intestinal failure, poor growth and neurodevelopmental delay. Besides prevention, there have been hardly any innovations in the treatment of NEC which underwent trial evaluation.
NEC pathogenesis is multifactorial, but bowel ischemia is known to play an essential role in the development of NEC. Remote ischemic conditioning (RIC) is a therapeutic maneuver that involves brief cycles of non-lethal ischemia and reperfusion applied to a limb, which protects distant organs (such as the intestine) from ischemic damage. The investigators have shown that in preclinical models of NEC, RIC effectively reduces intestinal damage and prolongs survival. The investigators have also demonstrated the safety of RIC in preterm neonates with NEC. Before the investigators can evaluate the effectiveness of RIC in treating neonates with NEC in a Phase III randomized clinical trial (RCT), a Phase II Feasibility RCT must be conducted to evaluate issues related to the enrollment and randomization of neonates, masking of the RIC intervention, and measurement of clinical outcomes.
The investigators hypothesize that it is feasible to conduct a multicenter RCT to evaluate RIC during the management of neonates with medical NEC.
详细描述
Background: Necrotizing enterocolitis (NEC) is a serious intestinal disease of preterm and term neonates which remains a major cause of intestinal failure, and an unsolved clinical challenge in pediatrics resulting in mortality rates as high as 50%, reduced quality of life and long-term disabilities such as short bowel syndrome, poor growth, and neurodevelopmental delay. Experimentally, the investigators have discovered that intestinal and brain damage, as well as mortality following NEC, can be avoided by remote ischemic conditioning (RIC) in the early stage of the disease. Remote ischemic conditioning is a therapeutic maneuver involving brief cycles of non-lethal ischemia and reperfusion applied to a limb that protects distant organs (such as the intestine) from sustained ischemic damage. In the clinical setting, the cycles of ischemia and reperfusion can be administered by inflation and deflation of a blood pressure cuff, similar to routine blood pressure measurements. The investigators have also demonstrated that this non-invasive, simple, and easy-to-use maneuver consisting of inflation/deflation of a blood pressure cuff on the upper arm is safe in preterm human neonates with NEC.
Hypothesis and Objectives: The investigators hypothesize that a masked multi-center randomized controlled trial of RIC in neonates with early-stage NEC is feasible.
Study design: This is a Phase II multicenter, masked, randomized controlled feasibility trial consisting of two arms: RIC (intervention) and no RIC (control).
Study population: Preterm neonates with clinical and radiological evidence of early-stage NEC and receiving medical treatment.
Sample size/power of primary endpoint: In the 12 international collaborating centers, the investigators expect to randomize, in 30 months, 78 patients with NEC receiving medical treatment (39 per arm) which represents 40% of approached eligible neonates.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
RIC will be masked from the local team of healthcare workers and parents/caregivers. A trained research fellow/nurse not involved in the circle of care will perform, behind a portable sliding medical privacy screen, inflation/deflation of the cuff (RIC intervention) or sham inflation/deflation of the cuff connected to a dummy neonatal arm to mimic the noise of cuff inflation (control). Both limbs (receiving and not receiving RIC) will be blinded from the circle of care and parents/caregivers. During the RIC procedure, the research fellow/nurse will monitor the oxygen saturation of the limb receiving RIC via pulse oximetry. The circle of care will continue to monitor the neonate's clinical parameters on the cardiopulmonary monitor on the other side of the privacy screen.
入排标准
- 年龄范围
- 0 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All gestational age at birth.
- •Current weight ≥600 g
- •Confirmed diagnosis of "medical" NEC based on the joint opinion of two attending experts in the field (two neonatologists or one neonatologist and one pediatric surgeon).
- •NEC diagnosis established within the previous 24 hours.
排除标准
- •Indication for surgery in the joint opinion of the attending neonatologist and pediatric surgeon (i.e. surgical NEC). This diagnosis is based on the presence of pneumoperitoneum in the abdominal radiograph and/or failure of medical treatment for NEC
- •Previous episodes of NEC
- •Diagnosis of NEC established >24 hours ago
- •Major congenital heart disease which needs surgical repair
- •Antecedent limb ischemia/limb thrombotic events, occlusive arterial or venous thrombosis
- •Associated gastrointestinal anomalies including gastroschisis or congenital diaphragmatic hernia.
研究组 & 干预措施
Intervention (RIC + standard of care for NEC)
Neonates randomized to the intervention arm will receive RIC and will continue to receive the standard of care for NEC.
干预措施: Remote ischemic conditioning (RIC) + Standard of Care for NEC (Other)
Control (Standard of care for NEC)
Neonates randomized to the control arm will receive the standard of care for NEC. The research fellow or nurse responsible for performing RIC will be performing sham inflation/deflation of the blood pressure cuff connected to a dummy arm to mimic the noise of the cuff for neonates in the control arm.
干预措施: Standard of Care for NEC (Other)
结局指标
主要结局
The proportion (% total) of randomized patients that receive allocated intervention.
时间窗: 72 hours
The investigators will determine the proportion (% total) of patients randomized to each study arm who successfully receive the intervention corresponding to that arm: RIC or no RIC.
The proportion (% total) of screened patients that are eligible for enrollment in the trial.
时间窗: 24 hours
The investigators will determine the proportion (% total) of screened patients who meet the inclusion criteria and do not meet the exclusion criteria and are therefore eligible for enrollment in this study.
The proportion (% total) of randomized patients receiving masked allocated intervention.
时间窗: 72 hours
The investigators will determine the proportion (% total) of randomized patients that receive the allocated intervention (RIC or no RIC) successfully masked from the circle of care as well as parents/caregivers.
The proportion (% total) of eligible patients that give consent and are randomized.
时间窗: 24 hours
The investigators will determine the proportion (% total) of eligible patients for whom informed consent from parents/caregivers can be obtained and randomization can be completed within 24 hours from confirmed diagnosis of medical NEC by a neonatologist and pediatric surgeon.
The proportion (% total) of randomized patients assessed for NEC-related outcomes.
时间窗: 3 months +/- 1 week
The investigators will determine the proportion (% total) of randomized patients that are successfully assessed for the NEC-related outcomes (please see secondary outcomes 6-13 below).
次要结局
- Number, type and times of abdominal operations performed.(3 months +/- 1 week)
- Number of patients developing severe retinopathy of prematurity (ROP)(3 months +/- 1 week)
- Timing and cause of death(3 months +/- 1 week)
- Number of patients surviving without the development of intestinal perforation, necrosis or stricture.(3 months +/- 1 week)
- Number of patients receiving parenteral nutrition(3 months +/- 1 week)
- Survey of stakeholders' satisfaction(1 month +/- 1 week)
- Number of patients developing severe neurological injury(3 months +/- 1 week)
- Number of patients developing chronic lung disease (CLD)(3 months +/- 1 week)
研究者
Agostino Pierro
Principal Investigator
The Hospital for Sick Children