Posaconazole Noninferior to Voriconazole for Primary Treatment of Invasive Aspergillosis

Word Aspergillosis on a paper and pills on the wooden table.
Study authors assessed the noninferiority of posaconazole to voriconazole for the primary treatment of invasive aspergillosis.

Posaconazole was non-inferior to voriconazole for the primary treatment of invasive aspergillosis, according to an international, randomized, double-blind, double-dummy, controlled non-inferiority trial published in the Lancet.

Between October 25, 2013, and September 10, 2019, investigators randomly assigned 585 participants to receive either posaconazole or voriconazole. In the posaconazole group, 288 participants received intravenous (IV) or oral (PO) posaconazole 300 mg twice daily on day 1, followed by 300 mg daily thereafter. In the voriconazole group, 297 participants received voriconazole 6 mg/kg IV or 300 mg PO twice daily on day 1 followed by 4 mg/kg IV or 200 mg PO twice daily thereafter.

The primary endpoint of this study was all-cause mortality until day 42, with day 1 as the first day of treatment regardless of the duration of study treatment in the intention-to-treat population. Safety, incidences of treatment-emergence adverse events, treatment-related adverse events, and serious adverse events were monitored.

Study authors observed the primary outcome in 44 participants (15%) in the posaconazole group and 59 participants (21%) in the voriconazole group (treatment difference, -5.3%; 95% CI, -11.6 to 1.0). This result indicated posaconazole was non-inferior to voriconazole because the upper limit of the 95% CI was lower than the prespecified 10% noninferiority margin set by the study authors.

The majority of participants experienced at least 1 treatment-emergence adverse event. However, study authors determined fewer adverse events were drug-related in the posaconazole group (30%) compared with the voriconazole group (40%; treatment difference, -10.2%; 95% CI, -17.9 to -2.4). Visual disturbances are the most common treatment-related adverse events reported with voriconazole use. Study authors found a lower proportion of treatment-related eye disorders occurring in the posaconazole group (2%) compared with the voriconazole group (10%; treatment difference, -8.0%; 95% CI, -12.2 to -4.5). Overall, study authors note that posaconazole was better tolerated than voriconazole.

Limitations for this trial include the absence of therapeutic drug monitoring and inability to decrease voriconazole dose for toxicity management.

 “Safety limitations of posaconazole include the need for careful monitoring of electrolytes and hepatic function throughout a course of therapy,” the study authors concluded.


Maertens JA, Rahav G, Lee DG, et al; on behalf of the study investigators. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. Lancet. Published online February 6, 2021. doi:10.1016/S0140-6736(21)00219-1.