A randomised controlled trial to determine whether skin barrier enhancement with emollients can prevent eczema in high risk children

WHY WE WANT TO DO THIS TRIAL: Childhood eczema affects one in five UK schoolchildren. Constant itching causes misery and sleep loss to children and families. Children with eczema also develop more food allergies, asthma and allergic rhinitis. Genetics and the environment are important in causing eczema and associated allergies. An imbalance in the immune system and a defective skin barrier at birth may both be important in increasing the risk of eczema. Mutations in the genes that code for filaggrin proteins (FLG) that are essential to maintaining a healthy skin barrier have consistently been shown to result in dry skin in early life plus an increased risk of eczema, severity of eczema and associated asthma. Regular application of emollients (skin moisturisers) enhance the skin barrier, but it is not known if enhancing the skin barrier from birth can reduce the onset and severity of eczema or associated allergic diseases. WHAT WE HAVE DONE TO PREPARE FOR THIS TRIAL: We conducted an overview of systematic reviews of randomised controlled trials (RCTs) on the primary prevention of eczema and showed that none of the dietary or allergen reduction interventions clearly prevented eczema. In our pilot RCT (part of our NIHR Programme Grant) we randomised 124 babies to daily emollients plus skin care advice for 6 months or skin care advice alone and showed that families were willing to take part in such a study and that contamination of the control group was low. Encouragingly, it also showed that daily emollients halved the risk of eczema developing. We have also done biomechanical studies on the skin of people with a history of eczema and shown that the two of the most popular emollients in the pilot study improve skin barrier function, and so we will use these in this main trial. WHAT WE PLAN TO DO IN THIS TRIAL: We would like to test the hypothesis that daily emollient application for 12 months after birth can reduce the onset of eczema at age 2 years. Our secondary aims are to see whether this simple, low-cost intervention can reduce the severity distribution of eczema, delay the onset of eczema that does develop, and the development of associated allergic diseases (asthma, allergic rhinitis and food allergies), whether it is cost effective and whether any effects last into later childhood. HOW WE PLAN TO DO IT: Design: A pragmatic, randomised, controlled, parallel group, multicentre, assessor-blind primary prevention trial. Health technologies being assessed: All parents will be given best practice infant skin care advice for their child. Those randomised to the intervention group will, in addition, be advised to apply emollient daily to the child’s entire body surface area for the first year of life (either Doublebase Gel® and Diprobase Cream® and may change between the two emollients throughout the trial if they wish). Measurement of outcomes: The primary outcome is a diagnosis of eczema between 12 and 24 months of age (defined as meeting the UK Working Party Diagnostic criteria). To reflect the chronicity of eczema, these criteria refer to signs and symptoms present over the past year. Applying the criteria at 24 months of age will therefore detect eczema present only between the ages of 12 and 24 months, thus excluding transient eczematous rashes which are common in the first year of life and often reported by parents as “eczema” but less likely to be true atopic eczema. Secondary outcomes are other measures of the development of eczema (parental report of a clinical diagnosis, parental completion of UK Working Party Diagnostic Criteria, and visible eczema at 2 years of age), severity of eczema, presence of other allergic diseases, quality of life, health care resource use and cost effectiveness, and safety endpoints (slippages and skin infections). We will continue to follow the children up to age of 5. Setting: Participating families will be recruited in approximately 10 centres around the UK from primary and secondary care as well as through general publicity and advertising. Target population: Babies at high risk of developing eczema and associated allergic disease, defined as having a parent or sibling who has (or had) doctor diagnosed asthma, eczema or allergic rhinitis. Sample size: Assuming that 30% of children in the control group will have eczema between one and two years of age and that a relative reduction of 30% is deemed to be of clinical importance (i.e. 21% of children in the intervention group have eczema between one and two years of age), a total of 1282 children will allow this difference to be detected at the 5% significance level (two-sided) with 90% power. This assumes equal numbers of children randomised to each group and 20% attrition. WHY IT IS IMPORTANT TO DO THIS STUDY: It is timely to conduct this trial as knowledge of skin barrier function and its relationship to eczema has expanded rapidly in the last 5 years and our pilot RCT results are promising.