Efficacy and safety of a 4-step versus a 5-step egg ladder in children with IgE-mediated hen's egg protein allergy: protocol for an open-label randomized controlled trial.

Background: Introducing baked egg into the diet of children with hen's egg allergy (HEA) has been shown to potentially accelerate the development of tolerance to non-heated egg. However, there is no standardized egg ladder (EL) protocol, and different scientific societies across countries recommend varying versions. This study aims to assess the efficacy and safety of the four-step EL (4-EL) compared with the five-step EL (5-EL) in children with IgE-mediated HEA.

Methods: We will perform an open-label randomized trial with two-parallel arms in two departments if the same academic hospital. A total of 84 children with IgE-mediated HEA will be allocated in 1:1 ratio to introduce hen's egg allergy into their diet according to either 4-EL or 5-EL with 4-week break period between subsequent steps. Oral food challenge (OFC) with tested products at each subsequent step of the EL will be conducted in hospital settings. The primary outcome will be the percentage of children with tolerance to non-heated hen's egg proteins defined as non-allergic reaction to raw hen's egg (0.5-1 egg, depending on the age of the patient) during the last OFC; measured at the end of the 18-week observation period for the 4-EL and 24-week observation period for the 5-EL. Secondary outcomes will include the percentage of children with negative OFC to each EL step; the percentage of children with anaphylaxis (including the percentage of those who were treated with epinephrine); the percentage of children with exacerbation of atopic dermatitis; growth; compliance; and quality of life of the caregivers and parents anxiety about adverse events during their child's OFC.

Discussion: This rigorously designed RCT will provide evidence on the efficacy and safety of the 4-EL in children with IgE-mediated HEA. The findings will inform guideline development groups and further confirmatory trials.

Trial registration number: NCT07040111, date of registration: 27 June 2025.