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.