Remote ischemic conditioning in necrotizing enterocolitis: study protocol of a multi-center phase II feasibility...

Area of Science:

• Neonatal medicine
• Surgical research
• Cardiovascular research

Background:

• Remote ischemic conditioning (RIC) involves brief limb ischemia-reperfusion cycles.
• RIC has shown promise in experimental necrotizing enterocolitis (NEC) by improving intestinal microcirculation.
• Previous studies indicated RIC is safe in neonates with NEC.

Purpose of the Study:

• Evaluate the safety and feasibility of RIC in neonates with NEC.
• Identify challenges in patient recruitment and retention for RIC trials.
• Inform the design of a future Phase III Randomized Controlled Trial (RCT) to assess RIC efficacy.

Main Methods:

• A Phase II multicenter, masked, feasibility RCT involving 12 international centers.
• RIC intervention: four cycles of 4-min limb ischemia followed by 4-min reperfusion on two consecutive days.
• Primary endpoint: feasibility and acceptability of recruitment, randomization within 24 hours of NEC diagnosis, masking, and intervention completion.

Main Results:

• An international NEC consortium was formed with consensus on diagnostic criteria and trial protocol.
• Inclusion criteria: gestational age < 33 weeks, weight ≥ 750g, medically treated NEC diagnosed within 24 hours.
• Expected recruitment: 40% of eligible patients (78 neonates) over 30 months, analyzed using Bayesian methods.

Conclusions:

• A novel NEC consortium has been established, generating data on NEC diagnosis and defining feasibility parameters for RIC.
• This Phase II RCT provides crucial information for designing a future Phase III RCT.
• The study will inform the evaluation of RIC's efficacy and safety in early-stage NEC.