Phase IV, open-label study of intravenous anidulafungin followed optionally by oral voriconazole for treatment of candidaemiainvasive candidiasis in critically ill patients
Abstract number: P2125
Nucci M., Petti M., Magana M., Abreu P., Sanchez S.
Objectives: To evaluate the efficacy, safety and impact on mortality of short-course intravenous (IV) anidulafungin (ANID), followed optionally by oral voriconazole (VORI), in critically ill patients with candidemia/invasive candidiasis (C/IC).
Methods: Phase IV, multicentre, open-label, non-comparative trial. Patients received ANID 200 mg IV on Day 1 and 100 mg IV ANID daily thereafter. Oral VORI (400 mg BID loading dose, 200 mg BID thereafter) was permitted if control of fungal infection was confirmed at Day 5 of IV treatment. The primary endpoint of the study was global response rate (clinical + microbiological response) at end of therapy (EOT). Secondary endpoints included: global response rate at end of IV treatment (EIVT), 30-day survival, C/IC-related mortality and species distribution. Safety assessments included adverse events (AEs), and changes in clinical and laboratory parameters.
Results: In total, 54 patients were enrolled from six countries across Latin America (59.3% female, mean (SD) age 52.8 (17.4) years, mean APACHE-II score 14.7), from a target sample size of 210 patients. Median total duration of exposure (ANID±VORI) was 15 days (range 1 37); 16 patients (29.6%) were switched to oral VORI. The most common species isolated was C. albicans (25/52 [48.1%]); C. parapsilosis was isolated from 7/52 patients (13.5%) and C. glabrata from 5/52 (9.6%) patients. Global response rate for the modified intent-to-treat population (study drug + positive Candida within 96 h of study entry) at EOT was 59.1% (26/44 patients: 95% CI: 44.6, 73.6) for the primary endpoint with missing/indeterminate set to failure, and 83.9% (26/31 patients; 95% CI: 70.9, 96.8) for a sensitivity analysis with missing/indeterminate excluded. On day 30, the mortality rate was 43.2% (19/44). On the last evaluation, 4 deaths (9.1% of patients [N = 44]) were attributed to C/IC. The most common AE was septic shock (20.4%; all unrelated to ANID). Only 17/204 AEs were considered ANID-related (12/54 patients [22.2%]). Two AEs with fatal outcome (hyperkalemia and drug ineffective) were considered ANID-related.
Conclusions: The safety of ANID in critically ill patients was comparable to the known profile of ANID. Initial results from this small study suggest that short-course ANID, followed by optional oral VORI, might be effective for the treatment of C/IC, including the reduction of C/IC-associated mortality, in Latin America. Further studies are warranted.
|Session name:||Abstracts of 21st ECCMID / 27th ICC|
|Location:||Milan, Italy, 7 - 10 May 2011|
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