Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial.
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Vanderbeke Lore, Janssen Nico A F, Bergmans Dennis C J J, Bourgeois Marc, Buil Jochem B, Debaveye Yves, Depuydt Pieter, Feys Simon, Hermans Greet, Hoiting Oscar, van der Hoven Ben, Jacobs Cato, Lagrou Katrien, Lemiale Virginie, Lormans Piet, Maertens Johan, Meersseman Philippe, Mégarbane Bruno, Nseir Saad, van Oers Jos A H, Reynders Marijke, Rijnders Bart J A, Schouten Jeroen A, Spriet Isabel, Thevissen Karin, Thille Arnaud W, Van Daele Ruth, van de Veerdonk Frank L, Verweij Paul E, Wilmer Alexander, Brüggemann Roger J M, Wauters Joost, Dutch-Belgian Mycosis Study Group
Аннотация
METHODS: We compared 7 days of intravenous posaconazole (POS) prophylaxis with no prophylaxis (standard-of-care only, SOC) in a randomised, open-label, proof-of-concept trial in patients admitted to an intensive care unit (ICU) with respiratory failure due to influenza (ClinicalTrials.gov, NCT03378479). Adult patients with PCR-confirmed influenza were block randomised (1:1) within 10 days of symptoms onset and 48 h of ICU admission. The primary endpoint was the incidence of IAPA during ICU stay in patients who did not have IAPA within 48 h of ICU admission (modified intention-to-treat (MITT) population).
RESULTS: Eighty-eight critically ill influenza patients were randomly allocated to POS or SOC. IAPA occurred in 21 cases (24%), the majority of which (71%, 15/21) were diagnosed within 48 h of ICU admission, excluding them from the MITT population. The incidence of IAPA was not significantly reduced in the POS arm (5.4%, 2/37) compared with SOC (11.1%, 4/36; between-group difference 5.7%; 95% CI - 10.8 to 21.7; p = 0.32). ICU mortality of early IAPA was high (53%), despite rapid antifungal treatment.
CONCLUSION: The higher than expected incidence of early IAPA precludes any definite conclusion on POS prophylaxis. High mortality of early IAPA, despite timely antifungal therapy, indicates that alternative management strategies are required. After 48 h, still 11% of patients developed IAPA. As these could benefit from prophylaxis, differentiated strategies are likely needed to manage IAPA in the ICU.