Safety
Tree nuts have the potential to trigger severe allergic reactions in susceptible children and there is a risk of reaction in both the multi nut and home introduction arms of the TreEAT trial. To date there is a paucity of data on the type and severity of tree nut reactions in infancy and on first exposure. However, low risk of severe reactions on first exposure have been reported to peanut [26] and it has been suggested that the risk of severe reactions may be age related [17]. Our published data for cashew nut challenges indicate that <2% of positive cashew nut challenges involve the development of anaphylaxis [27].
In the home introduction arm, the risk and severity of potential reactions will be minimised by following the cautious graded home introduction protocol with dose escalation daily. All participants will be provided with an ASCIA Allergy Action Plan [28] outlining the signs and symptoms of an allergic reaction, and appropriate treatment including the use of antihistamines and adrenaline auto injectors if required. This information is also included on the Home introduction of tree nuts TreEAT trial information provided to families.
It is not known if giving tree nuts together in a mixed nut butter in the multi nut OFC group may increase the risk or severity of an allergic reaction. However, the overall dose of each tree nut protein in the multi-nut butter is lower than that given in an individual nut OFC (1g versus 2-4g depending on OFC top dose). The risks are mitigated with specialised allergy trained nursing and medical staff supervising the OFCs and anaphylaxis rescue medication (adrenaline) and full resuscitation equipment on standby. Additionally, the multi-nut OFCs will be done in the Melbourne Children’s Trial Centre which is co-located at Australia’s largest tertiary paediatric children’s hospital, Royal Children’s Hospital Melbourne.
There is a risk of discomfort and minor bruising, swelling or bleeding following a blood test. Finally, there is the inconvenience to the families of attending clinic and possible additional OFC appointments. We assess that the study benefits outweigh the potential risks.