Infant Reflux Trial: study protocol for a multicentre randomized controlled trial on the treatment of gastroesophageal reflux disease in infants.

backgroundGastroesophageal reflux disease (GERD) is a common condition in infants below 1 year of age. Symptoms include frequent regurgitation, failure to thrive, food refusal, irritability, and back arching. While many infants experience some degree of physiological reflux, persistent or severe symptoms may indicate GERD. One important underlying cause of GERD in infants is allergy to cow's milk protein. Current international guidelines recommend a trial of a cow's milk protein-free diet prior to initiating medical therapy with a proton-pump inhibitor. However, the efficacy of both the diet and the medication remains insufficiently studied. With only a few randomized trials available, further evidence is needed to ensure infants receive the most appropriate treatment.

methodsThis protocol describes a multicentre, randomized placebo-controlled trial, enrolling 96 infants with a clinical diagnosis of GERD at 3 paediatric centres in Southern Denmark. Eligible participants will be randomly assigned to one of three parallel groups: (1) A diet group receiving a cow's milk protein-free diet, (2) a medicine group treated with a proton-pump inhibitor, and (3) a control group receiving a placebo medicine. Both the PPI group and the control group will be blinded to the allocation and will continue a diet containing cow's milk protein. The intervention period is 4 weeks. The primary outcome is the reduction in the number of regurgitation episodes. Secondary outcomes include weight gain and reduction in GERD-related symptoms. Symptom data will be reported by parents using a digital application, and specific IgE to cow's milk protein will be quantified in all participants. Infants in the diet group who respond positively will undergo an oral milk challenge to confirm allergy to cow's milk protein. DISCUSSION: This trial is designed to provide evidence on the efficacy of a cow's milk protein-free diet and proton-pump inhibitor therapy for infant GERD. Both interventions are evaluated against a control group, ensuring that any improvement exceeds the natural course of symptom resolution over time. The findings will provide valuable insights to guide clinical practice and enhance treatment strategies for infant GERD, a condition with a substantial impact on infant health and family well-being. PROSPECTIVE

trial registrationClinicalTrials.gov NCT06255886. Registered on February 13, 2024. CLINICALTRIALS: eu EU-CT: 2022-502770-16-00. Registered on November 4, 2024.