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.
OBJECTIVE
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.
Division of Infectious Diseases, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA. corey001@mc.duke.edu
G Ralph
GR
Corey
Mark H
MH
Wilcox
George H
GH
Talbot
Dirk
D
Thye
David
D
Friedland
Tanya
T
Baculik
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001398:Aztreonam / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008875:Middle Aged; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult; D000097583:Ceftaroline
D000900:Anti-Bacterial Agents; D001398:Aztreonam; D002511:Cephalosporins; D014640:Vancomycin; D000097583:Ceftaroline