Background: Isavuconazole, a new triazole with broad-spectrum antifungal activity, was compared to
caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational
clinical trial (ACTIVE; NCT00413218) for safety and efficacy in patients with proven candidemia or
invasive candidiasis (IC).
Material/methods: Adults were randomized 1:1 to isavuconazole (200mg IV TID for two days,
followed by 200mg IV QD) or caspofungin (70 mg IV QD on Day 1, followed by 50 mg IV QD) for a
maximum of 56 days. After day 10, qualified patients could switch to oral isavuconazole
(isavuconazole-arm) or voriconazole (caspofungin-arm). Documentation of infection and outcomes
were assessed by an independent Data-Review Committee. Daily blood cultures were collected
through Day 9. Primary efficacy endpoint was successful overall response (based on successful
clinical and mycological responses, and no use of alternative systemic antifungal therapy post end of
treatment) at the end of IV therapy (EOIV) in patients with proven infection who received ≥1 dose of
study drug (modified intent-to-treat [mITT] population). The pre-specified non-inferiority margin was
15%. The key secondary outcome (mITT) was successful overall response at end of treatment + 2
weeks (FU1). All-cause mortality (ACM) at Day 14 and 56 and safety were also assessed.
Results: 450 patients were randomized; 400 patients comprised the mITT population. Baseline
characteristics were balanced between the groups. The primary endpoint of successful overall
response at EOIV (isavuconazole, n/N=120/199 [60.3%]; caspofungin, n/N=143/201 [71.1%]; adjusted
difference [95%CI]: -10.8 [-19.9, -1.8]) did not meet the noninferiority margin. The key secondary
endpoint, all-cause mortality and other outcomes were similar in both arms (Table). Safety results
were comparable between the groups (Table).
Conclusions: The primary endpoint was not met; however, the key secondary endpoint was similar
between the two groups. Both drugs were safe and well tolerated.
Full conference title:
- ECCMID 26th (2016)