2.1. Study Design and Population
ICH, Breastfed
SECONDARY
The study was designed as a prospective, multicentre, randomised, double-blind, parallel-group, controlled, non-inferiority trial. It was carried out from March to October 2021 in 21 centres in four European countries (11 in Bulgaria, one in Germany, eight in Hungary, and one in the Czech Republic). The study was conducted in accordance with ICH Good Clinical Practice and the Declaration of Helsinki as well as with the local legal and regulatory requirements. It was approved by the corresponding ethics committees and registered at ClinicalTrials.gov (NCT04736082).Healthy term infants from singleton pregnancies whose mothers intended to exclusively feed either formula or human milk were eligible for participation. Further details on inclusion and exclusion criteria have been described elsewhere [Upon written informed consent of both parents or legal guardians (further referred to as “parents” only), eligible formula-fed infants were enrolled into the study and randomised to one of the two infant formula-fed (FF) groups (i.e., eHF or CF). Randomisation was carried out in a double-blinded dynamic manner using country and sex as stratification variables via a centralised randomisation management interface. Breastfed infants were assigned to a non-randomised breastfed reference group (BF).The presented evaluation of the secondary parameters representing GI tolerance includes the period from enrolment up to 120 days of age. After enrolment (≤25 days of age; V0), infants attended four study visits at 30 ± 3 (V1), 60 ± 3 (V2), 90 ± 3 (V3), and 120 ± 3 (V4) days of age. Exclusive infant formula feeding began no later than 26 days of age and was continued until at least V4.