G Ralph Corey1, Samantha Good2, Hai Jiang2, Greg Moeck2, Matthew Wikler2, Sinikka Green3, Paul Manos4, Richard Keech5, Rajesh Singh6, Barry Heller7, Natalia Bubnova8, William O'Riordan9. 1. Duke University Medical Center, Durham, North Carolina. 2. The Medicines Company, Parsippany, New Jersey. 3. Sharp Grossmont Hospital, San Diego. 4. Paradise Valley Hospital, Oceanside. 5. Physician Alliance Research Center, Anaheim, California. 6. Government Medical College, Nagpur, India. 7. Novo Research, Long Beach, California. 8. St George the Martyr City Hospital, St Petersburg, Russia. 9. Sharp Chula Vista Medical Center, California.
Abstract
BACKGROUND:Oritavancin is a lipoglycopeptide antibiotic with rapid bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and long half-life allow for single-dose treatment. METHODS: In a randomized, double-blind trial, adults with acute bacterial skin and skin structure infections (ABSSSIs) received either a single intravenous 1200-mg dose of oritavancin or 7-10 days of twice-daily vancomycin. Three efficacy endpoints were tested for noninferiority: (1) primary composite endpoint at 48-72 hours (cessation of spreading or reduction in lesion size, absence of fever, and no rescue antibiotic); (2) investigator-assessed clinical cure 7-14 days after end of treatment; and (3) ≥20% reduction in lesion area at 48-72 hours. RESULTS:A total of 503 and 502 patients comprised the modified intent-to-treat population for oritavancin and vancomycin, respectively. All 3 efficacy endpoints met the 10% noninferiority margin: the primary composite endpoint (80.1% vs 82.9%; 95% confidence interval [CI], -7.5 to 2.0), investigator-assessed clinical cure (82.7% vs 80.5%; 95% CI, -2.6 to 7.0), and proportion of patients attaining ≥20% reduction in lesion area (85.9% vs 85.3%; 95% CI, -3.7 to 5.0) for oritavancin vs vancomycin, respectively. Efficacy outcomes by pathogen, including methicillin-resistant Staphylococcus aureus and the frequency of adverse events, were similar between treatment groups. CONCLUSIONS: A single 1200-mg dose of oritavancin was noninferior to 7-10 days of vancomycin in treating ABSSSIs caused by gram-positive pathogens, and was well tolerated. Oritavancin provides a single-dose alternative to multidose therapies for the treatment of ABSSSIs. Clinical Trials Registration. NCT01252732.
RCT Entities:
BACKGROUND:Oritavancin is a lipoglycopeptide antibiotic with rapid bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and long half-life allow for single-dose treatment. METHODS: In a randomized, double-blind trial, adults with acute bacterial skin and skin structure infections (ABSSSIs) received either a single intravenous 1200-mg dose of oritavancin or 7-10 days of twice-daily vancomycin. Three efficacy endpoints were tested for noninferiority: (1) primary composite endpoint at 48-72 hours (cessation of spreading or reduction in lesion size, absence of fever, and no rescue antibiotic); (2) investigator-assessed clinical cure 7-14 days after end of treatment; and (3) ≥20% reduction in lesion area at 48-72 hours. RESULTS: A total of 503 and 502 patients comprised the modified intent-to-treat population for oritavancin and vancomycin, respectively. All 3 efficacy endpoints met the 10% noninferiority margin: the primary composite endpoint (80.1% vs 82.9%; 95% confidence interval [CI], -7.5 to 2.0), investigator-assessed clinical cure (82.7% vs 80.5%; 95% CI, -2.6 to 7.0), and proportion of patients attaining ≥20% reduction in lesion area (85.9% vs 85.3%; 95% CI, -3.7 to 5.0) for oritavancin vs vancomycin, respectively. Efficacy outcomes by pathogen, including methicillin-resistant Staphylococcus aureus and the frequency of adverse events, were similar between treatment groups. CONCLUSIONS: A single 1200-mg dose of oritavancin was noninferior to 7-10 days of vancomycin in treating ABSSSIs caused by gram-positive pathogens, and was well tolerated. Oritavancin provides a single-dose alternative to multidose therapies for the treatment of ABSSSIs. Clinical Trials Registration. NCT01252732.
Authors: John H Powers; Donald L Patrick; Marc K Walton; Patrick Marquis; Stefan Cano; Jeremy Hobart; Maria Isaac; Spiros Vamvakas; Ashley Slagle; Elizabeth Molsen; Laurie B Burke Journal: Value Health Date: 2017-01-10 Impact factor: 5.725
Authors: Abraham Pulido-Cejudo; Mario Guzmán-Gutierrez; Abel Jalife-Montaño; Alejandro Ortiz-Covarrubias; Jose Luis Martínez-Ordaz; Héctor Faustino Noyola-Villalobos; Luis Mauricio Hurtado-López Journal: Ther Adv Infect Dis Date: 2017-08-31
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