Рандомизированное контролируемое исследование RIC-NEC (RIC-NEC)

Neonates randomized to the intervention arm will receive RIC and will continue to receive the standard of care for NEC.

RIC will consist of 4 cycles of limb ischemia (5 min) followed by reperfusion (5 min), repeated on two consecutive days. An appropriately sized blood pressure cuff (covering 2/3 of the distance between the shoulder and the elbow) will be applied by a trained research fellow or nurse to an arm (or leg if the arm is not available because of medical reasons such as central line insertion). The systolic blood pressure will be measured before the first RIC cycle using a different cuff of same size connected to a monitor. During ischemia time, the cuff will be inflated to a pressure of 15 mmHg above the child's systolic pressure. Neonates in this arm will continue to receive 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.

Neonates in this arm (i.e. the control arm) will receive standard of care for NEC.

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 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 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 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 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).

The investigators will determine the number of randomized patients who survive at 1 month and 3 months post-randomization without developing intestinal perforation, intestinal necrosis, or intestinal stricture.

The time, and if possible, the cause of death will be recorded during the 90 days post-randomization considering whether it was possible to determine if death was related to complications of NEC or to a disease process in other systems including cardiac, neurological, respiratory, renal, metabolic.

The number, time(s), and type(s) of abdominal operations (insertion of peritoneal drainage or laparotomy) performed during the 90 days post-randomization will be recorded.

The number of patients receiving parenteral nutrition during the 90 days post-randomization will be recorded as a measure of intestinal function.

Development of severe neurological injury will be assessed based on head ultrasound at 1-month and 3-months post-randomization and will be defined as the presence of intraventricular hemorrhage (IVH), ventricular enlargement, parenchymal echogenicity or periventricular leucomalacia (PVL).

Development of chronic lung disease (CLD) during the 90 days post-randomization will be defined as respiratory support given at 36 weeks' postmenstrual age or at discharge (if earlier than 36 weeks' postmenstrual age) to level 2 neonatal intensive care unit (NICU) and classified in different degrees of severity from mild to moderate to severe CLD according to the criteria published in the Canadian Neonatal Network (CNN) Annual Report (2019).

During the 90 days post-randomization, the investigators will assess the development of Stage 3, 4 or 5 retinopathy of prematurity (ROP) as defined by the International Classification of ROP and/or those infants requiring treatment (laser or intraocular injection). ROP will be scored as the highest stage in either eye identified at any time.

Satisfaction of key trial stakeholders (parents and healthcare workers) with the recruitment process, delivery and masking of the intervention will be evaluated by questionnaires, using a scale of 0-4. Higher scores indicate greater satisfaction and lower scores indicate less satisfaction.