A pooled analysis of 2 parallel, phase 3, double-blind, randomized (1:1), active-controlled, multinational, multicenter trials (REVIVE-1 and REVIVE-2) included a total of 602 patients with wound infections treated with iclaprim, a novel dihydrofolate reductase inhibitor with a low propensity for resistance development and rapid bactericidal activity in vitro and a targeted spectrum of activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus.
The data were analyzed separately and then pooled to determine the efficacy of iclaprim 80 mg fixed dose compared with vancomycin 15 mg/kg. Both drugs were administered intravenously every 12 hours for 5 to 14 days according to the investigator assessment of clinical response. The primary end point of these studies was to determine whether iclaprim was noninferior (10% margin) to vancomycin in achieving a ≥20% reduction in lesion size (early clinical response) at 48 to 72 hours after initiation of the study drug (early time point), compared with baseline in the intent-to-treat population.
Of the 50% (602/1198) of patients treated in the REVIVE-1 and -2 studies with wound infections, 51% were treated with iclaprim and 49% were treated with vancomycin. Similar demographic and baseline characteristics were observed in the 2 arms of the pooled REVIVE studies with the exception of fewer diabetics and more illicit drug users in the iclaprim arm. Iclaprim had similar early clinical response (83.5%) at the early time point compared with vancomycin (79.7%) among the subset of patients with wound infections. In this post-hoc analysis of the 2 REVIVE studies, iclaprim achieved noninferiority to vancomycin in the subgroup of patients with wound infections.
Source: Huang D, et al. IDWeek 2018. Abstract 1338.