Remote Ischemic Conditioning in Necrotizing Enterocolitis

Study Overview
=================
Brief Summary
-----------------
Necrotizing enterocolitis (NEC) affects up to 10% of very preterm infants. NEC mortality is high (30-50 %) and has remained unchanged over the last decades. New treatments are urgently needed. NEC pathogenesis is multifactorial, but bowel ischemia plays an essential role in NEC development. Remote ischemic conditioning (RIC) consists in inducing brief periods of non-lethal ischemia in a limb distant to an organ suffering from ischemia. RIC has been used in adults, children and term neonates with a variety of diagnosis. However, no study has been done including preterm infants with NEC.

Detailed Description
-----------------
An appropriately sized blood pressure cuff will be applied to an arm or leg and inflated to promote RIC. This study will be conducted in three phases to assess the feasibility and safety of RIC in relation to duration of ischemia time, number of cycles of RIC and whether it is feasible and safe to perform RIC on consecutive days.

Official Title
-----------------
Remote Ischemic Conditioning in Necrotizing Enterocolitis: Feasibility and Safety Pilot Study.

Conditions
-----------------
Enterocolitis, Necrotizing

Intervention / Treatment
-----------------
* Procedure: Remote ischemic conditioning


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with NEC (stages I-III Bell's Classification) Weight greater or equal to 750 g. Gestational age < 36 weeks. Patients whose parents consent to participate in the study. Exclusion Criteria: Patients with major congenital anomalies No antecedent of limb ischemia/limb thrombotic events. No antecedent diagnosis of occlusive arterial or venous thrombosis Hemodynamic instability

Ages Eligible for Study
-----------------
Minimum Age: 0 Months
Maximum Age: 3 Months

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Remote ischemic conditioning|An appropriately sized blood pressure cuff will be inflated around a limb (systolic blood pressure + 15 mmHg) for different periods of time (1 to up to 4 minutes), times (1 to up to 4 times) and consecutive days (1 to up to 2).|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Limb perfusion after Remote Ischemic Conditioning | Limb perfusion will be assessed before (baseline) and after Remote Ischemic Conditioning (RIC). Limb perfusion will be determined by oxygen saturation using pulse oximetry. RIC will be considered feasible and safe if the procedure is completed as planned with no failure of limb re-perfusion. Failure is defined as no return of limb arterial oxygen saturation to baseline 4 minutes after the ischemic phase (re-perfusion time). | 1 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cutaneous injury | Defined as new-onset skin breakdown, bruising, ecchymosis or petechiae. | 1 days | 
| Persistent pain | Pain measured according to the premature infant pain profile (PIPP) scores (range 0-21). Pain scores will be obtained immediately before (baseline) and 6 hours after RIC. Persistent pain will be defined as a PIPP score higher than the baseline score. | 1 days |