CANVAS 2: the second Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections

Autor: Maria Antonia Mastruzzo, Sergey Shlyapnikov, Edgars Zarembo, Rodney Mason, Claudia G. Rodríguez, John Pullman, Vladimir Samonte, Carolina Chain, Rudolf Schandalik, Larry Bush, Álvaro Llancaqueo, Mario Calvo, Igor S. Osipov, Carlos E. Bergallo, Malgorzata Gutowska-Jablonska, Luis Jauregui-Peredo, Boris G. Bezrodny, Dieter Bachter, G. Ralph Corey, Peter Kohl, Joseph DeSanto, Joseph Surber, Krzysztof Kolomecki, Jane N. Zuckerman, Waclaw Majewski, Artur Timmerman, Christopher Lucasti, Mark H. Wilcox, Christian G. Remolif, Ilona Hartmane, Javier Altclas, Slawomir Rudzki, Victors Lovcinoskis, Marek Drazkiewicz, George H. Talbot, Jan Kulig, Martin Schilling, Franz Trautinger, Alexander V. Konychev, Volodymyr V. Ganzhyi, Antonio Tarcisio de Faria Freire, Andrejs Pavars, David Friedland, Dirk Thye, Artur Hartwich, Oleksiy B. Datsenko, Alexander M. Shulutko, Christian Schrock, Tanya Baculik, Patrick C. Lee, Gerardo Amaya, Janis Gardovskis, Paul Manos, Soledad Lee, Thomas Sheftel, James Guetzkow, Piotr Szyber, Eduardo Rodríguez, Harold C. Standiford, Sergio Edwardo Prieto, Oleksandra V. Stasyshyn, Graciana Isabel Morera
Rok vydání: 2010
Předmět:
Zdroj: The Journal of antimicrobial chemotherapy. 65
ISSN: 1460-2091
Popis: Objectives New therapies for complicated skin and skin structure infections (cSSSIs) are needed because of significant morbidity and increasing antimicrobial resistance. Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of cSSSIs. Ceftaroline fosamil, a novel parenteral cephalosporin with excellent in vitro activity against Gram-positive pathogens, including MRSA, and many Gram-negative pathogens, was evaluated as therapy for cSSSIs in a multinational Phase III study. The primary study objective was to determine non-inferiority [lower limit of 95% confidence interval (CI), -10%] in the clinical cure rate of ceftaroline fosamil monotherapy to that achieved with vancomycin plus aztreonam combination therapy in the clinically evaluable (CE) and modified intent-to-treat (MITT) analysis populations. Methods Adult patients with cSSSIs requiring intravenous therapy received 600 mg of ceftaroline fosamil every 12 h or 1 g of vancomycin plus 1 g of aztreonam every 12 h for 5-14 days (randomized 1 : 1). Clinical and microbiological response, adverse events (AEs) and laboratory tests were assessed. Registration number NCT00423657 (http://clinicaltrials.gov/ct2/show/NCT00423657). Results The study enrolled 694 patients, 348 of whom received ceftaroline fosamil and 346 of whom received vancomycin plus aztreonam. The treatment groups had comparable baseline characteristics. Clinical cure rates for the ceftaroline fosamil and vancomycin plus aztreonam groups were similar in the CE (92.2%, 271/294 versus 92.1%, 269/292; 95% CI, -4.4, 4.5) and MITT (85.1%, 291/342 versus 85.5%, 289/338; 95% CI, -5.8, 5.0) populations, respectively. MRSA cSSSIs were cured in 91.4% (64/70) of patients in the ceftaroline fosamil group and 93.3% (56/60) of patients in the vancomycin plus aztreonam group. The microbiological success rate in the microbiologically evaluable population was 92.9% and 95.0% for ceftaroline fosamil and vancomycin plus aztreonam, respectively. Ceftaroline fosamil and vancomycin plus aztreonam had similar rates of AEs, serious AEs and discontinuations because of an AE. The most common AEs for ceftaroline fosamil and vancomycin plus aztreonam included diarrhoea (6.5% versus 4.4%), nausea (6.2% versus 5.6%), headache (5.3% versus 5.3%) and pruritus (3.8% versus 8.3%), respectively. Conclusions Ceftaroline fosamil demonstrated high clinical cure and microbiological success rates, was efficacious against cSSSIs caused by MRSA and other common cSSSI pathogens and was generally well tolerated. Monotherapy with ceftaroline fosamil has the potential to provide an alternative treatment for cSSSIs.
Databáze: OpenAIRE
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