D1.286 - Nebulized inhaled epinephrine versus epinephrine autoinjector for the treatment of food-induced anaphylaxis in young children – a randomized controlled clinical trial

Anaphylaxis is a severe, life-threatening allergic reaction that requires immediate medical attention. Epinephrine administration as the most critical treatment for anaphylaxis is usually performed intramuscularly. However, there is strong hesitancy for autoinjector use, especially among caregivers, and a need for effective needle-free options. Pharmacokinetic studies in healthy volunteers indicate that systemic absorption of highly concentrated nebulized inhaled epinephrine is rapid and has a good bioavailability, thus can reach therapeutic levels, but data on affected young children was lacking. The observer-blinded, randomized, controlled TRANCHE clinical trial (TReatment of ANaphylaxis in CHildren with Epinephrine, EudraCT 2014-000097-19) investigated the effectiveness, safety and bioavailability of highly concentrated inhaled nebulized epinephrine vs. epinephrine autoinjector use in young children with acute anaphylactic reaction during an oral food challenge.

Children of one to six years of age undergoing a medically indicated oral food challenge were included in the trial, to be randomized in case of anaphylaxis. Children meeting the criteria for anaphylaxis as outlined by Sampson et. al. (2006) were randomized to be treated with either continuous inhalation of nebulized epinephrine (4 mg L-epinephrine/ml) or autoinjector use (epinephrine 150 µg). Additional treatment options did not differ between both groups. An additional dose of intramuscular epinephrine was possible at any moment if clinically mandated. After 10 and 20 minutes, independent assessments for the necessity of a second dose of epinephrine were done by a second study physician blinded to the original treatment. The children were monitored in hospital for at least 24 hours after treatment.

141 children were enrolled, and 26 children experiencing anaphylaxis during the oral food challenge were randomized for epinephrine treatment, 13 for inhalation, 13 for autoinjector. All children recovered from anaphylaxis. Only one child, initially treated with autoinjector, required additional intramuscular epinephrine. 

It is possible to safely conduct a clinical trial of treatment options in young children experiencing anaphylaxis during an oral food challenge. In the TRANCHE clinical trial, highly concentrated inhaled nebulized epinephrine was as effective in treating anaphylaxis as the autoinjector. 

Funding: InfectoPharm and institutional funds.