Objectives: Isavuconazole (ISA) is a novel, water-soluble, broad-spectrum triazole antifungal developed for treatment of invasive fungal disease (IFD). In contrast to ISA, current triazole antifungal IV formulations contain diluents that cause side-effects in renally-impaired patients. We report outcomes by renal-impairment status in a pooled population of patients with invasive aspergillosis (IA) enrolled in two Phase 3 multi-centre trials and who received ISA treatment.
Methods: SECURE (NCT00412893) was a randomised, double-blind, parallel-group, non-inferiority trial that assessed efficacy and safety of ISA vs. voriconazole in adult patients with IFD caused by Aspergillus spp. and other filamentous fungi. VITAL (NCT00634049) was an open-label, single-arm trial that evaluated efficacy and safety of ISA for treatment of IA in adult patients with renal impairment, and IFD caused by emerging moulds, yeasts, and dimorphic fungi. Eligibility criteria are available at clinicaltrials.gov. The ISA dosing regimen in each trial was 200mg (IV/oral) TID for 2 days, then 200mg QD (IV/oral). Proven/probable IFD (EORTC/MSG criteria) and overall response at end of treatment (EOT) were determined by independent data-review committees (DRC). Mortality rates, safety and tolerability were also analysed. The primary outcome was all-cause mortality (ACM) through Day 42. This subgroup analysis evaluated IA patients with and without baseline renal-impairment, as defined by guidelines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative as a glomerular filtration rate (GFR) of <60 mL/min/1.73 m2.
Results: Of the 527 patients randomised in SECURE and 149 patients enrolled in VITAL, a total of 143 patients with proven/probable IA treated with ISA were analysed: 31 had renal impairment and 112 had no renal impairment (Table). Day 42 ACM, Day 84 ACM, DRC-assessed overall response at EOT, and safety and tolerability were comparable between patient groups. 2
Conclusion: Outcomes and safety and tolerability were comparable between IA patients with and without renal impairment, treated with ISA.