Remote ischemic conditioning in premature neonates with necrotizing enterocolitis

NEC is an intestinal disease that primarily affects premature and medically fragile infants. The development of NEC is associated with a hole in the gut or dead gut due to reduced oxygen supply to the gut.

RIC is a treatment strategy whereby cycles of inflating a blood pressure cuff around a limb (to occlude blood flow), followed by deflating the cuff to remove occlusion, can protect a distant organ (such as the small intestine) from damage due to reduced blood flow and compromised oxygen supply.

Our pre-clinical studies have shown that RIC can improve blood flow and oxygen supply to the intestine with NEC. By improving blood flow to the intestine, RIC can reduce the intestinal damage due to NEC in early stages of the disease before irreversible intestinal damage has occurred. Therefore, RIC may be able to help babies with NEC recover by enhancing the blood flow and oxygen arriving at the gut.

Our clinical studies show that in 15 babies with NEC Sick Children (Toronto, CA), RIC was safe and caused no complications or adverse events. However, the safety of RIC has not been yet evaluated in a larger population. This is one of the goals of this clinical trial.

The image shows a baby with NEC receiving RIC. RIC is done via a blood pressure cuff placed around the upper arm and inflated and deflated for 4 cycles.

There are three main knowledge gaps related to the successful design of a Phase III RCT to evaluate whether RIC can effectively treat babies with NEC.: (1) A large number of Phase III pediatric trials fail due to flaws in study design, insufficient recruitment of patients, or inappropriate statistical endpoints. The only two trials on NEC treatment failed due to suboptimal recruitment; (2) The outcomes for NEC are poorly defined and are partly influenced by subjectivity; and (3) We do not know whether it is feasible to perform an RCT on RIC in babies with NEC. A Phase II RCT is necessary before embarking on a precisely powered multicenter international Phase III RCT to evaluate, on a large scale, the effectiveness of RIC in the treatment of babies with early-stage NEC.

This study aims to determine whether it is safe and feasible to give RIC to babies with NEC, within 24 hours of confirmed diagnosis of NEC by a neonatologist and pediatric surgeon.