PMID- 21115454 OWN - NLM STAT- MEDLINE DCOM- 20110314 LR - 20231213 IS - 1460-2091 (Electronic) IS - 0305-7453 (Linking) VI - 65 Suppl 4 DP - 2010 Nov TI - CANVAS 1: the first Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. PG - iv41-51 LID - 10.1093/jac/dkq254 [doi] AB - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a common cause of complicated skin and skin structure infections (cSSSIs). Increasing antibiotic resistance and significant morbidity in cSSSIs have led to a need for new effective and safe therapies. 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 large multicentre study. The primary study objective was to determine non-inferiority [lower limit of 95% confidence interval (CI), -10%] in the clinical cure rate achieved with ceftaroline fosamil monotherapy compared with that achieved with vancomycin plus aztreonam in the clinically evaluable (CE) and modified intent-to-treat (MITT) patient 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 NCT00424190 (http://clinicaltrials.gov/ct2/show/NCT00424190). RESULTS: Of 702 enrolled patients, 353 received ceftaroline fosamil and 349 received vancomycin plus aztreonam. Baseline characteristics of treatment groups were comparable. Clinical cure rates were similar for ceftaroline fosamil and vancomycin plus aztreonam in the CE (91.1%, 288/316 versus 93.3%, 280/300; 95% CI, -6.6, 2.1) and MITT (86.6%, 304/351 versus 85.6%, 297/347; 95% CI, -4.2, 6.2) populations, respectively. The clinical cure rate for MRSA cSSSIs was 95.1% (78/82) for ceftaroline fosamil and 95.2% (59/62) for vancomycin plus aztreonam. The microbiological success rate was also similar for ceftaroline fosamil and vancomycin overall, and for MRSA. The rates of AEs, serious AEs, deaths and discontinuations because of an AE were similar for ceftaroline fosamil and vancomycin plus aztreonam. The most common AEs for ceftaroline fosamil and vancomycin plus aztreonam were diarrhoea (3.4% versus 3.2%), nausea (5.7% versus 4.6%), headache (5.1% versus 3.7%) and pruritus (3.1% versus 8.4%), respectively. CONCLUSIONS: Ceftaroline fosamil achieved high clinical cure and microbiological success rates, was efficacious for cSSSIs caused by MRSA and other common cSSSI pathogens and was generally well tolerated. Ceftaroline fosamil has the potential to provide a monotherapy alternative for treatment of cSSSIs. FAU - Corey, G Ralph AU - Corey GR AD - Division of Infectious Diseases, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA. corey001@mc.duke.edu FAU - Wilcox, Mark H AU - Wilcox MH FAU - Talbot, George H AU - Talbot GH FAU - Thye, Dirk AU - Thye D FAU - Friedland, David AU - Friedland D FAU - Baculik, Tanya AU - Baculik T CN - CANVAS 1 investigators LA - eng SI - ClinicalTrials.gov/NCT00424190 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - J Antimicrob Chemother JT - The Journal of antimicrobial chemotherapy JID - 7513617 RN - 0 (Anti-Bacterial Agents) RN - 0 (Cephalosporins) RN - 6Q205EH1VU (Vancomycin) RN - G2B4VE5GH8 (Aztreonam) SB - IM MH - Adult MH - Aged MH - Anti-Bacterial Agents/administration & dosage/pharmacology/*therapeutic use MH - Aztreonam/administration & dosage/adverse effects/therapeutic use MH - Cephalosporins/administration & dosage/adverse effects/*therapeutic use MH - Double-Blind Method MH - Drug Therapy, Combination MH - Humans MH - Methicillin-Resistant Staphylococcus aureus/drug effects MH - Middle Aged MH - Skin Diseases, Bacterial/*drug therapy/microbiology MH - Soft Tissue Infections/*drug therapy/microbiology MH - Staphylococcal Infections/drug therapy/microbiology MH - Treatment Outcome MH - Vancomycin/administration & dosage/adverse effects/therapeutic use MH - Young Adult MH - Ceftaroline FIR - Mehra, Purvi IR - Mehra P FIR - Alpert, Marc IR - Alpert M FIR - Baird, Ian IR - Baird I FIR - Klein, Stanley IR - Klein S FIR - Litow, Jeffrey IR - Litow J FIR - Marsh, Peter IR - Marsh P FIR - Penn, Robert IR - Penn R FIR - Augustinsk, James IR - Augustinsk J FIR - Young, David IR - Young D FIR - Bunce, Christopher IR - Bunce C FIR - Green, Daniel IR - Green D FIR - Eyzaguirre, Robert IR - Eyzaguirre R FIR - Ambasch, German IR - Ambasch G FIR - Curcio, Daniel J IR - Curcio DJ FIR - Lopardo, Gustavo IR - Lopardo G FIR - Minguez, Angel R IR - Minguez AR FIR - Oliva, Maria E IR - Oliva ME FIR - Teglia, Osvaldo F IR - Teglia OF FIR - Campos, Maria IR - Campos M FIR - Gaete, Pablo IR - Gaete P FIR - Acuna, Guillermo IR - Acuna G FIR - Jansen, Luis IR - Jansen L FIR - Jauregui, Arturo IR - Jauregui A FIR - Perez, Carlos IR - Perez C FIR - Seas, Carlos IR - Seas C FIR - Gutierrez, Jorge IR - Gutierrez J FIR - Mayorga, Manuel IR - Mayorga M FIR - Bubnova, Natalia A IR - Bubnova NA FIR - Goryunov, Sergey V IR - Goryunov SV FIR - Krylov, Konstantin M IR - Krylov KM FIR - Macheret, Evgeny A IR - Macheret EA FIR - Novozhilov, Andrey A IR - Novozhilov AA FIR - Zhidkov, Konstantin P IR - Zhidkov KP FIR - Kozlov, Roman S IR - Kozlov RS FIR - Florescu, Ioan P IR - Florescu IP FIR - Orasan, Remus IR - Orasan R FIR - Trifu, Viorel IR - Trifu V FIR - Ockenfels, Hans-Michael IR - Ockenfels HM FIR - Hermes, Barbara IR - Hermes B FIR - Brockmeyer, Norbert IR - Brockmeyer N FIR - Dippel, Edgar IR - Dippel E FIR - Kujath, Peter IR - Kujath P FIR - Kowalzick, Lutz IR - Kowalzick L FIR - Ulrich, Jens IR - Ulrich J FIR - Krasnodebski, Ireneusz IR - Krasnodebski I FIR - Jaworski, Roman IR - Jaworski R FIR - Zaniewski, Maciej IR - Zaniewski M FIR - Wallner, Grzegorz IR - Wallner G FIR - Kapinska-Mrowiecka, Monika IR - Kapinska-Mrowiecka M FIR - Dziki, Adam IR - Dziki A FIR - Motyka, Marek IR - Motyka M FIR - Borschivsky, Viktor M IR - Borschivsky VM FIR - Gerych, Ihor D IR - Gerych ID FIR - Lukashov, Serhiy M IR - Lukashov SM FIR - Pyptyuk, Oleksandr V IR - Pyptyuk OV EDAT- 2010/12/09 06:00 MHDA- 2011/03/15 06:00 CRDT- 2010/12/01 06:00 PHST- 2010/12/01 06:00 [entrez] PHST- 2010/12/09 06:00 [pubmed] PHST- 2011/03/15 06:00 [medline] AID - dkq254 [pii] AID - 10.1093/jac/dkq254 [doi] PST - ppublish SO - J Antimicrob Chemother. 2010 Nov;65 Suppl 4:iv41-51. doi: 10.1093/jac/dkq254.