David B Huang1, Thomas M File2, Antoni Torres3, Andrew F Shorr4, Mark H Wilcox5, Paul Hadvary6, Matthew Dryden7, G Ralph Corey8. 1. Motif BioSciences, New York, New York. Electronic address: david.huang@motifbio.com. 2. Summa Health, Akron, Ohio. 3. Department of Pulmonology, Hospital Clinic of Barcelona, University of Barcelona, Institut D'investigacions August Pi I Sunyer, and Centro de Investigación Biomedica En Red-Enfermedades Respiratorias, Barcelona, Spain. 4. Section of Pulmonary and Critical Care Medicine, MedStar Washington Hospital Center, Washington, DC. 5. Leeds Teaching Hospitals and University of Leeds, Leeds, United Kingdom. 6. Hemex AG, Liestal, Switzerland. 7. Department of Microbiology and Infection, Hampshire Hospitals NHS Foundation Trust, Southampton, United Kingdom. 8. Duke University Medical Center, Durham, North Carolina.
Abstract
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.
RCT Entities:
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.
Authors: Thomas P Lodise; John Bosso; Colleen Kelly; Paul J Williams; James R Lane; David B Huang Journal: Antimicrob Agents Chemother Date: 2018-01-25 Impact factor: 5.191
Authors: Nicholas A Turner; Batu K Sharma-Kuinkel; Stacey A Maskarinec; Emily M Eichenberger; Pratik P Shah; Manuela Carugati; Thomas L Holland; Vance G Fowler Journal: Nat Rev Microbiol Date: 2019-04 Impact factor: 60.633
Authors: David B Huang; Ian Morrissey; Timothy Murphy; Stephen Hawser; Mark H Wilcox Journal: Eur J Clin Microbiol Infect Dis Date: 2017-12-08 Impact factor: 3.267
Authors: E M Aliouat; E Dei-Cas; N Gantois; M Pottier; C Pinçon; S Hawser; A Lier; D B Huang Journal: Eur J Clin Microbiol Infect Dis Date: 2018-01-12 Impact factor: 3.267
Authors: David B Huang; Catherine D Strader; James S MacDonald; Mark VanArendonk; Richard Peck; Thomas Holland Journal: Open Forum Infect Dis Date: 2018-01-06 Impact factor: 3.835
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