Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8738433 | International Journal of Antimicrobial Agents | 2018 | 33 Pages |
Abstract
Iclaprim, a diaminopyrimidine antimicrobial, was compared with vancomycin for treatment of patients with acute bacterial skin and skin-structure infections (ABSSSIs) in two studies (REVIVE-1 and REVIVE-2). Here, the efficacy and tolerability of iclaprim in a pooled analysis of results from both studies was explored. REVIVE-1 and REVIVE-2 were phase 3, double-blind, randomised, multicentre, active-controlled, non-inferiority (margin of 10%) trials, each designed to enrol 600 patients with ABSSSI using identical study protocols. Iclaprim 80 mg and vancomycin 15 mg/kg were administered intravenously every 12 h for 5-14 days. The primary endpoint was a â¥20% reduction from baseline in lesion size [early clinical response (ECR)] at the early time point (ETP) (48-72 h after starting study drug) in the intent-to-treat population. In REVIVE-1, ECR at the ETP was 80.9% with iclaprim versus 81.0% with vancomycin (treatment difference â0.13%, 95% CI â6.42% to 6.17%). In REVIVE-2, ECR was 78.3% with iclaprim versus 76.7% with vancomycin (treatment difference 1.58%, 95% CI -5.10% to 8.26%). The pooled ECR was 79.6% with iclaprim versus 78.8% with vancomycin (treatment difference 0.75%, 95% CI -3.84 to 5.35%). Iclaprim and vancomycin were comparable for the incidence of mostly mild adverse events, except for a higher incidence of elevated serum creatinine with vancomycin (nâ¯=â¯7) compared with iclaprim (nâ¯=â¯0). Iclaprim achieved non-inferiority compared with vancomycin for ECR at the ETP and secondary endpoints with a similar safety profile in two phase 3 studies for treatment of ABSSSI suspected or confirmed as caused by Gram-positive pathogens. [Clinical Trials Registration. NCT02600611 and NCT02607618.]
Keywords
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Authors
David B. Huang, G. Ralph Corey, Thomas L. Holland, Thomas Lodise, William O'Riordan, Mark H. Wilcox, Thomas M. Jr, Matthew Dryden, Barbara Balser, Eve Desplats, Antoni Torres,