Live biotherapeutic product IBP-9414 (L. reuteri) in very low birth weight infants: the Connection Study.

Abstract

Very low birth weight (VLBW) infants experience high rates of serious intestinal health outcomes, including death. The Connection Study evaluated the efficacy and safety of the live biotherapeutic product IBP-9414 (L. reuteri) versus placebo in necrotizing enterocolitis (NEC), sustained feeding tolerance (SFT), and all-cause mortality in this population. In this prospective, double-blind phase 3 trial, 2158 VLBW infants were randomized 1:1 to IBP-9414 or placebo within 48 hours of birth, with daily dosing until 34^6/7 weeks postmenstrual age. Primary endpoints were NEC incidence and time to SFT. Secondary endpoints included all-cause mortality incidence. IBP-9414 treatment compared with placebo did not result in statistically significant reductions in the primary endpoints, NEC incidence (relative risk [RR]: 0.85, p > 0.05) or time to SFT (hazard ratio: 1.10, p > 0.05). However, there was a reduction in all-cause mortality with IBP-9414 treatment, with mortality incidences of 6.2% in the IBP-9414 group versus 8.5% in the placebo group (RR: 0.73, p = 0.036). Adverse event rates were similar between the groups. There was no evidence of IBP-9414 in any blood culture. IBP-9414 treatment was safe and reduced mortality compared with placebo in vulnerable VLBW infants. The Connection Study provides evidence that the live biotherapeutic product IBP-9414 (L. reuteri) treatment was safe and reduced both mortality and surgically-confirmed  necrotizing enterocolitis (NEC) in vulnerable very low birth weight (VLBW) infants. The Connection Study findings support the use of IBP-9414 in VLBW infants and its potential to safely improve their intestinal mortality and morbidity.