A Phase II Randomized, Double-Blind, Multicenter Study to Evaluate Efficacy and Safety of Intravenous Iclaprim Versus Vancomycin for the Treatment of Nosocomial Pneumonia Suspected or Confirmed to be Due to Gram-Positive Pathogens

Purpose: The primary objective of this Phase II study was to compare the clinical cure rates of 2 iclaprim dosages versus vancomycin in the treatment of patients with nosocomial pneumonia suspected or confirmed to be caused by gram-positive pathogens. Methods: This study was a double-blind, randomized, multicenter trial. A total of 70 patients were randomized 1:1:1 to receive iclaprim 0.8 mg/kg IV q12h (iclaprim q12h; n = 23), iclaprim 1.2 mg/kg IV q8h (iclaprim q8h; n = 24), or vancomycin 1 g IV q12h (vancomycin; n = 23) for 7 to 14 days. The primary end point was clinical cure in the intention-to-treat population at test of cure (TOC; 7 [1] days’ posttreatment) visit. Findings: The baseline and demographic characteristics of patients treated with either iclaprim or vancomycin were comparable. Cure rates in the intention-to-treat population were 73.9% (17 of 23), 62.5% (15 of 24), and 52.2% (12 of 23) at the TOC visit in the iclaprim q12h, iclaprim q8h, and vancomycin groups, respectively (iclaprim q12h vs vancomycin, P = 0.13; iclaprim q8h vs vancomycin, P = 0.47). The death rates within 28 days of the start of treatment were 8.7% (2 of 23), 12.5% (3 of 24), and 21.7% (5 of 23) for the iclaprim q12h, iclaprim q8h, and vancomycin groups (no statistically significant differences). The adverse event profile of both iclaprim dosing regimens was similar to that of vancomycin. Implications: Iclaprim had clinical cure rates and a safety profile comparable with vancomycin among patients with nosocomial pneumonia. Iclaprim could be an important new therapeutic option for the treatment of nosocomial pneumonia, and a pivotal clinical trial is warranted to evaluate its safety and efficacy in this indication.