Isavuconazole Not Noninferior to Caspofungin for Invasive Candida Infections

Isavuconazole did not demonstrate noninferiority compared with caspofungin in the primary treatment of proven candidemia or invasive candidiasis, according to research published in Clinical Infectious Diseases.

 In this phase 3, randomized, double-blind, multinational clinical trial, 450 adult patients were randomly assigned in a 1:1 ratio to receive either isavuconazole (200 mg intravenously 3 times/day for 2 days, followed by 200 mg intravenously daily) or caspofungin (70 mg intravenously daily on day 1, followed by 50 mg intravenously daily [70 mg in patients >80 kg]) for a maximum of 56 days. After receiving 10 days of treatment, patients in the isavuconazole group were permitted to switch to oral isavuconazole and those in the caspofungin group were allowed to switch to oral voriconazole. The primary end point was a successful overall response at the end of intravenous therapy in the modified-intent-to-treat population (patients with proven infection who received ≥1 dose of study drug). The pre-specified non-inferiority was 15%.

 The modified-intent-to-treat population was 400 patients and the successful overall response at the end of intravenous therapy was 60.3% and 71.1% for the isavuconazole and caspofungin groups, respectively (adjusted difference -10.8; 95% CI -19.9 to -1.8). The secondary end points of safety and all-cause mortality at days 14 and 56 were similar for both groups and the median time to clearance of the bloodstream was also comparable.

The study did not include pediatric patients or patients with neutropenia. In addition, although the results supported observations that echinocandins are associated with fewer early efficacy failures, specific predictors of unfavorable outcomes with isavuconazole could not be identified.

In this study, there was no demonstration of noninferiority of isavuconazole relative to caspofungin for the primary treatment of candidemia and invasive candidiasis. The overall success rate of 82.6% for the 35% of those randomly assigned to isavuconazole who transitioned to oral treatment was however deemed favorable.

Reference

 Kullberg BJ, Viscoli C, Pappas PG, et al. Isavuconazole versus caspofungin in the treatment of candidemia and other invasive candida infections: the ACTIVE trial [published online October 5, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy827