498 - Correlating Sustained Feeding Tolerance (SFT) to Adverse Outcomes During Randomized Administration of L. reuteri for the Prevention of NEC and Improved Feeding Tolerance in Preterm Infants

Poster Number: 498
Publication Number: 498.425

Josef Neu, University of Florida, Gainesville, FL, United States; Jonas Rastad, Infant Bacterial Therapeutics, Stockholm, Stockholms Lan, Sweden; Marcus Thuresson, Infant Bacterial Therapeutics AB, Uppsala, Uppsala Lan, Sweden

Background: Endpoints of sustained feeding tolerance have not been validated against clinical outcomes in controlled studies of premature infants.

Objective: Determining a correlation between time to SFT and adverse outcomes may provide a valuable analytic tool in the efficacy analysis of enteral feeding regimens. 

Design/Methods: The Connection trial is a phase 3 study of the pharmaceutical grade probiotic IBP-9414 (Lactobacillus Reuteri) under US and EU INDs. In addition to NEC, the primary endpoint is the time from first dose of investigational product to SFT in infants of a birth weight (BW) of 500-1500 gr randomized 1:1 to a daily enteral dose of IBP-9414 (109 CFU) or placebo from within 48 hrs of birth till 34 w+6 d GA.A blinded analysis of how clinical outcomes correlate to SFT was performed for the first 248 infants with a BW of 750-1000 gr (mean 890 gr). SFT was defined as the first day of enteral feeds >120ml/kg body weight maintained for >10 consecutive days during which no parenteral nutrition was required and the mean body weight increased with mean >10 gr/kg/day.

Results: SFT was reached at mean 17.2 days (sd 10.4 days). Clinical outcomes associated with SFT were evaluated with linear regression models. They included NEC (p=0.0002), relevant gastrointestinal adverse events (AEs, p=0.0001), clinically suspected sepsis (p=0.0133), late onset sepsis (p=0.0001), bronchopulmonary dysplasia (p=0.036), retinopathy of prematurity (=0.0004), daily weight gain (p=0.0014), respiratory AEs (p < 0.0001), duration of hospitalization (p < 0.0001) and days with antibiotic medication (p < 0.0001). The number of adverse outcomes per subject increased in direct proportion to time to reach SFT.Conclusion(s): This blinded evaluation of very low BW infants underlines that several adverse outcomes strongly correlate to the time to SFT. We infer that SFT could be used as a surrogate marker for adverse outcomes in prospective randomized trials in preterm infants.