Objectives: Isavuconazole (ISA) is a novel, water-soluble, broad-spectrum, triazole antifungal agent developed for the treatment of invasive fungal disease (IFD). We present safety and outcomes in obese patients (body mass index [BMI] ≥30kg/m2) in the SECURE trial.
Methods: SECURE (NCT00412893) was a Phase 3, randomised, double-blind, parallel-group, non-inferiority trial that assessed the efficacy and safety of ISA vs. voriconazole (VRC) in patients with IFD caused by Aspergillus spp. and other filamentous fungi. Adult patients with proven/probable/possible IFD were randomised 1:1 to receive ISA or VRC for ≤84 days. Doses were: ISA 200mg IV TID for 2 days, then 200mg QD (IV/oral); VRC 6mg/kg IV BID on Day 1, 4mg/kg IV BID on Day 2, then 4mg/kg IV BID or 200mg oral BID. Dosing was based on actual body weight. The primary endpoint was all-cause mortality through Day 42. Overall success at end of treatment (EOT), as determined by an independent data-review committee, safety, and tolerability were also analysed. This analysis was conducted in patients with proven/probable IFD with BMIs <25, 25–<30, and ≥30kg/m2, treated with ISA or VRC.
Results: Of 527 patients randomised, 263 had proven/probable IFD and BMI data, including 25 obese patients with BMI ≥30kg/m2 (ISA, n=15; VRC, n=10) (Table). All-cause mortality through Day 42 was comparable between treatment arms in obese patients (adjusted difference: –13.3; 95% CI: –50.9, 24.2). Similar numbers of obese patients experienced an overall response of success in the ISA and VRC arms (adjusted difference: 0.0; 95% CI: – 49.4, 49.4). Drug-related treatment-emergent adverse events (TEAEs), serious TEAEs, and deaths were less frequent in obese patients treated with ISA vs. VRC.
Conclusion: ISA outcomes were comparable with VRC in this small subgroup of patients with BMI ≥30kg/m2, and similar to the other BMI subgroups. Drug-related TEAEs, serious TEAEs, and deaths were reported in fewer obese patients treated with ISA vs. VRC.