Research in Context
Evidence before this study
We searched PubMed without time or language limitation with the search criteria (“invasive”[All Fields] AND (“aspergillosis”[MeSH Terms] OR “aspergillosis”[All Fields])) AND ((“mortality”[Subheading] OR “mortality”[All Fields] OR “mortality”[MeSH Terms])) AND ((“registries”[MeSH Terms] OR “registries”[All Fields] OR “trial”[All Fields])), up to October, 2015. 55 references were found, of which 36 were categorised as clinical trials. By excluding prevention trials and studies in patients with Candida infections only, 15 clinical trials or cohorts or registries were identified, with nine studies before 2003. Mortality in all trials was similarly high. Only one study was well powered, prospective, and randomised-controlled prior to the beginning of the trial. Overall 10 studies were non-randomised or uncontrolled in nature; four studies were identified in patients refractory or intolerant to therapy; three trials included only patients with non-haematological disease (mainly solid organ transplant recipients). The only study published before 2003 was that by Herbrecht and colleagues (2002), which showed significantly improved outcomes, including survival advantage of voriconazole compared with conventional amphotericin B.
Added value of this study
SECURE is a prospective, double-blind, randomised, global trial demonstrating that the novel triazole isavuconazole is non-inferior to voriconazole for the primary treatment of invasive aspergillosis and disease caused by other moulds. Additionally, isavuconazole was well tolerated compared with voriconazole, with significantly fewer study drug-related adverse events and adverse events of the skin, eye, and hepatobiliary systems.
Implications of all the available evidence
Voriconazole is the current gold standard for treatment of invasive aspergillosis but is limited by drug–drug interactions and safety concerns. Moreover, many non-Aspergillus moulds, such as the agents of mucormycosis, are often resistant to voriconazole. This trial offers strong evidence that isavuconazole is an appropriate alternative to voriconazole for the primary treatment of invasive aspergillosis and other mould disease.