Efficacy and Safety of Polaprezinc/Zinc L-carnosine (Hepilor) in Infants With Gastroesophageal Reflux

This will be a randomised, single blind, controlled, study, designed to evaluate efficacy and safety of Zinc-L carnosine/Polaprezinc in infants (1-12 months of age) with symptoms suggestive of GER. The study will include a 2-week screening period, and a 8-week parallel arms treatment period. After the screening phase, eligible patients will be randomly assigned to either thickened formula or polaprezing twice a day, in a 1:1 ratio, for 8 weeks. Study visits will be conducted every 4 weeks during the treatment period. All the subjects will be blindly allocated by means of scratch cards to one of the two treatment groups according to a computer-generated randomisation list provided by our statistician. A validated program will be used by an independent statistician to generate a randomisation list with blocks, block size=4, pre-allocated to centres. Only study investigators will be blinderd to the randomisation codes. The codes will be kept confidential until the end of the study when the randomisation code will be broken after the database lock. All subjects will undergo a formal clinical assessment. The protocol will be approved by and indipendent etichs committee and conducted according to the Declaration of Helsinki and the principles of good clinical practice.

Eligible patients with symptoms meeting Rome IV criteria for diagnosis of Infant Regurgitation will be recruited from Sant'Andrea University Hospital and from Children Hospital SS Antonio E Biagio E C. Arrigo.

The estimated total sample size that was aimed was 48 (24 children per arm) with the power of 80% (alpha of 5%). We estimated a dropout rate of 20% and aimed to recruit 60 participants to provide at least 48 evaluable assessments.

Efficacy analysis will be performed on ITT population. A sensitivity analysis on PP population will be carried out only if 5% or more ITT subjects are excluded from PP population.

Comparison between the two groups will be performed according to ANCOVA model. For all ANCOVA models, the assumptions of normality and homogeneity of variance will be investigated. Violation of these assumptions will be overcome by performing a non-parametric test (the Wilcoxon Rank Sum test).