RIC-NEC Randomized Controlled Trial

Summary

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.

Conditions

• Necrotizing Enterocolitis

Interventions

OTHER

Remote ischemic conditioning (RIC) + 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.

OTHER

Standard of Care for NEC

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

Sponsors & Collaborators

• Thrasher Research Fund

  collaborator OTHER

• Mount Sinai Hospital, Canada

  collaborator OTHER

• Sunnybrook Health Sciences Centre

  collaborator OTHER

• McMaster Children's Hospital

  collaborator OTHER

• Children's Hospital Medical Center, Cincinnati

  collaborator OTHER

• Children's Hospital of Orange County

  collaborator OTHER

• Karolinska University Hospital

  collaborator OTHER

• Sophia Kindergeneeskunde

  collaborator OTHER

• UCL Great Ormond Street Institute of Child Health

  collaborator OTHER

• Hospital Universitario La Paz

  collaborator OTHER

• University of Southampton

  collaborator OTHER

• Xiamen Children's Hospital, Fujian of China

  collaborator OTHER

• Shanghai Children's Hospital

  collaborator OTHER

• The Hospital for Sick Children

  lead OTHER

Principal Investigators

• Agostino Pierro, OBE, MD · The Hospital for Sick Children

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

0 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-02-09

Primary Completion

2025-12-20

Completion

2026-03-18

Countries

• United States
• Canada

Study Locations