Behandling af gastroesofageal refluks sygdom hos spædbørn- et randomiseret studie Treatment of Gastroesophageal Reflux Disease in Infants- a Randomized Controlled Trial

The primary objective of this randomized controlled trial is to evaluate the **efficacy** of a cow's milk-free diet or proton pump inhibitor (PPI) treatment, specifically **omeprazole**, in infants under one year of age diagnosed with **Gastroesophageal Reflux Disease (GERD)**. The study aims to compare these interventions against a placebo by measuring the change from baseline in the weekly number of reflux episodes by the fourth week of treatment. This outcome is clinically relevant as it seeks to determine effective management strategies for GERD in this vulnerable population, potentially reducing the frequency of reflux episodes and improving infant health outcomes. The parents will record the number of reflux episodes daily using an application, ensuring accurate and consistent data collection.

The clinical trial focuses on infants diagnosed with **Gastroesophageal reflux disease (GERD)** and **cows' milk allergy**. The study population includes both male and female infants under the age of one year, with a specific age range starting from over one month old at the beginning of treatment. Participants are required to have at least three reflux episodes daily on average, accompanied by at least one troublesome symptom such as unexplained crying, discomfort or irritability, weight gain issues, feeding rejection, apnea, or back-arching. The trial involves a vulnerable population, as it includes infants. The sponsor has not provided information regarding the total number of participants. The trial aims to assess the efficacy of a cow's milk-free diet or proton pump inhibitors (PPI) on GERD in comparison to a placebo, with parents recording outcomes daily via an app. The selection criteria ensure that the study population is representative of infants experiencing GERD symptoms, with no specific lifestyle considerations such as diet or physical activity mentioned beyond the trial interventions.

The clinical trial is designed to evaluate the efficacy of a cow's milk-free diet or **proton pump inhibitor** (PPI) treatment on **gastroesophageal reflux disease** (GERD) in infants under one year of age, compared to a placebo. This study is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to commence on November 1, 2024, and conclude by December 31, 2025, with a maximum treatment period of six weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age under one year, a diagnosis of GERD with at least three reflux episodes daily, and the presence of specific troublesome symptoms. Following the screening, participants will be randomly assigned to one of the treatment groups: cow's milk-free diet, PPI, or placebo. The primary endpoint is the parent-reported reduction in the weekly number of reflux episodes after four weeks of treatment, with data collected daily via an app.

Secondary endpoints include various changes from baseline, such as weight, the number of reflux episodes with visible blood, and episodes of crying, discomfort, or breathing issues, all registered weekly. Follow-up visits will occur at regular intervals to monitor progress and collect data. The end-of-study visit will assess the overall outcomes and any adverse events reported during the trial. Participants are expected to be involved for the full six-week treatment period unless early termination is warranted due to adverse events or withdrawal of consent.

The clinical trial involves the administration of **Omeprazole**, a proton pump inhibitor, formulated as a powder for oral suspension. The active substance, **omeprazole**, is of chemical origin and is identified by the EU substance number SUB09439MIG. The pharmaceutical form is specifically designed for oral use, ensuring ease of administration in the target population. The dosing regimen is calculated based on body weight, with a maximum daily dose of 1.7 mg/kg and a total maximum dose of 71.4 mg/kg over the treatment period. The treatment duration is capped at six weeks, with the primary objective being to assess the efficacy of the medication in reducing the frequency of reflux episodes in infants diagnosed with gastroesophageal reflux disease (GERD).

In addition to the active treatment, the study employs a placebo control, which is a powder for oral suspension identical in appearance to the active formulation but devoid of the active substance. The placebo is administered following the same dosing schedule as the active treatment, ensuring blinding and maintaining the integrity of the study design. The placebo is crucial for evaluating the true efficacy of the active treatment by providing a baseline for comparison. Participant compliance with the dosing regimen is monitored through daily entries by parents in a designated application, which records the frequency of reflux episodes and ensures adherence to the study protocol.

The efficacy of the treatment for **Gastroesophageal Reflux Disease (GERD)** in infants will be assessed through a randomized controlled trial. The primary endpoint for evaluating efficacy is the change from baseline in the weekly number of reflux episodes in the active treatment groups compared to the control group (placebo) after four weeks of treatment. This outcome will be parent-reported and registered daily using an application.

Secondary endpoints include various parent-reported outcomes, such as the reduction in the number of reflux episodes in the proton pump inhibitor (PPI) group compared to the diet group, changes in weight, and the number of reflux episodes with visible blood. Additional secondary endpoints involve changes from baseline in episodes of crying, refusal of breast or bottle, short breathing pauses, paleness or blue color in the face or lips, troublesome breathing or cough, and discomfort, all registered weekly in the MyCap App. Immunoglobulin E levels will be measured to assess cow's milk allergy, with values above 0.35 kU/l considered positive. Adverse events related to the trial medicine will also be monitored and reported weekly.

Measurements for weight changes will be conducted by a nurse or physician using a scale in a clinical or hospital setting. The trial will also include an oral provocation test with cow's milk for infants in the diet group who show improvement, conducted in a hospital setting, with symptoms recorded by a nurse and parents reporting any late symptoms via phone call 48 hours post-test. The trial is designed to ensure comprehensive data collection and analysis to evaluate the efficacy of the treatments under investigation.