A pooled analysis of patients with wound infections in the Phase 3 REVIVE trials: randomized, double-blind studies to evaluate the safety and efficacy of iclaprim versus vancomycin for treatment of acute bacterial skin and skin structure infections.

Introduction. Iclaprim is a diaminopyrimidine antibiotic for the treatment of acute bacterial skin and skin structure infections (ABSSSI) due to Gram-positive pathogens. Aim. This analysis evaluates patients with wound infections from two Phase 3 trials of ABSSSI. Methodology. Six-hundred-two patients with wound infections from two Phase 3, double-blinded, randomized, multicenter. active controlled trials (REVIVE-1/-2) were evaluated in a post hoc analysis of iclaprim 80 mg compared with vancomycin 15 mg kg(-1) administered intravenously every 12 h for 5-14 days. The primary endpoint was to determine whether iclaprim was noninferior (10% margin) to vancomycin in achieving a >= 20% reduction from baseline in lesion size 48-72h after starting study drug (early clinical response [ECR]). Safety was assessed. Results. In REVIVE-1, ECR was 83.5% with iclaprim versus 79.7% with vancomycin (treatment difference 3.77%, 95% CI -4.50%, 12.04%). In REVIVE-2, ECR was 82.7% with iclaprim versus 76.3% with vancomycin (treatment difference 6.38%, 95% CI -3.35%, 16.12%). In the pooled dataset, iclaprim had similar ECR rates compared with vancomycin among wound infection patients (83.2% vs 78.2%) with a treatment difference of 5.01 % (95% CI -1.29%.11.32%). The safety profile was similar in iclaprim- and vancomycin-treated patients, except for a higher incidence of diarrhea with vancomycin (n=17) compared with iclaprim (n=6) and fatigue with iclaprim (n=17) compared with vancomycin (n=8). Conclusion. Based on early clinical response, iclaprim achieved non-inferiority to vancomycin with a similar safety profile in patients with wound infections suspected or confirmed as caused by Gram-positive pathogens. Iclaprim may be a valuable treatment option for wound infections.