Phase IV clinical trial with a single treatment arm to evaluate bronchopulmonary penetration of isavuconazole in pulmonary transplant recipients (PBISA01): Study protocol clinical trial. (Preprint)

BACKGROUND Aspergillosis is the most frequently observed invasive fungal disease (IFD) in lung transplant recipients. Isavuconazole has shown a better safety profile and non-inferiority to voriconazole in the treatment of patients with IFD. OBJECTIVE The aim of this study is to describe the bronchopulmonary pharmacokinetic profile of oral isavuconazole by analyzing the degree of penetration in the epithelial lining fluid and the alveolar macrophages in patients receiving lung transplantation with a diagnosis of invasive fungal disease. METHODS A total of 12 patients over 18 years of age, lung transplant recipients with IFD diagnosis and indication for isavuconazole treatment and follow-up bronchoscopy will be included in the study. After 5 days of treatment with isavuconazole and before the treatment is discontinued, patients will be randomized to perform the scheduled bronchoscopy at different times from the administration of Isavuconazole (2, 4, 8, 12 hours). Four blood samples will be obtained per patient: at 72 h after treatment initiation, the day of the bronchoscopy, at the time of the BAL (simultaneously) and 7 days after treatment initiation, in order to analyse tacrolimus and isavuconazole plasma levels. Isavuconazole concentrations will be measured in plasma, epithelial lining fluid (ELF) and alveolar macrophages (CA) by a high-performance liquid chromatography/UV couple to Fluorescence method. RESULTS Recruitment is ongoing. No preliminary data have been yet obtained. CONCLUSIONS There are no clinical studies that analyze the bronchopulmonary penetration of isavuconazole. Bronchoalveolar lavage (BAL) performed routinely in the follow-up of lung transplant recipients, constitutes an opportunity to analyze the bronchopulmonary penetration of isavuconazole. CLINICALTRIAL This clinical trial has been registered on the European Clinical Trials Register (www.clinicaltrialsregister.eu), and the registration number is 2019-004240-30.