Study design and oversight
The study was conducted as an open, prospective, observational, multicenter study (Clinicaltrials.gov number NCT04269629). Patients were recruited in 26 centers in eight European countries. The study was approved by the ethics committee of the sponsor of the study (Medical University of Graz; approval no. 26-442 ex 13/14) as well as local ethics committees in each country, and patients gave their written, informed consent.
Legally competent male and female patients aged 35 to 85 years with a history of an SSR (≥ grade I according to the classification by Ring and Messmer18) were eligible for the study. Absolute contraindications to VIT and pretreatment with Omalizumab were exclusion criteria.
After giving their written informed consent, patients were included after carefully reviewing all inclusion and exclusion criteria at Visit 1. All data concerning the index sting reaction, laboratory parameters like specific immunoglobulin E (sIgE) and tryptase levels and skin test results were recorded as well as concomitant diseases and medication. If patients agreed to receive VIT, data concerning the up-dosing phase (premedication, venom preparation, up-dosing protocol, systemic AE (classification by Ring and Messmer18), changes in concomitant diseases, and medication) were recorded at Visit 2. There was no standard up-dosing protocol used for VIT. All centers used their own in-house protocols including conventional, cluster, ultrarush- and rush-protocols.5 One year after reaching the maintenance dose, Visit 3 was performed. At this visit, changes in premedication, venom preparation, concomitant diseases and medication were recorded as well as systemic AE during the maintenance phase and, if applicable, the outcome of field stings and/or sting challenges. No additional study-related visits were required. All procedures (diagnosis and treatment of Hymenoptera venom allergy) had to be in concordance with current EAACI guidelines5,19,20 and were conducted individually by each study center.