Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection.
BACKGROUND
Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated skin and skin-structure infection (cSSSI). Increasing antimicrobial resistance in cSSSI has led to a need for new safe and effective therapies. Ceftaroline was evaluated as treatment for cSSSI in 2 identical phase 3 clinical trials, the pooled analysis of which is presented here. The primary objective of each trial was to determine the noninferiority of the clinical cure rate achieved with ceftaroline monotherapy, compared with that achieved with vancomycin plus aztreonam combination therapy, in the clinically evaluable (CE) and modified intent-to-treat (MITT) patient populations.


METHODS
Adult patients with cSSSI requiring intravenous therapy received ceftaroline (600 mg every 12 h) or vancomycin plus aztreonam (1 g each every 12 h) for 5-14 days.


RESULTS
Of 1378 patients enrolled in both trials, 693 received ceftaroline and 685 received vancomycin plus aztreonam. Baseline characteristics of the treatment groups were comparable. Clinical cure rates were similar for ceftaroline and vancomycin plus aztreonam in the CE (91.6% vs 92.7%) and MITT (85.9% vs 85.5%) populations, respectively, as well as in patients infected with MRSA (93.4% vs 94.3%). The rates of adverse events, discontinuations because of an adverse event, serious adverse events, and death also were similar between treatment groups.


CONCLUSIONS
Ceftaroline achieved high clinical cure rates, was efficacious against cSSSI caused by MRSA and other common cSSSI pathogens, and was well tolerated, with a safety profile consistent with the cephalosporin class. Ceftaroline has the potential to provide a monotherapy alternative for the treatment of cSSSI.


BACKGROUND
ClinicalTrials.gov identifiers: NCT00424190 for CANVAS 1 and NCT00423657 for CANVAS 2.
Corey
G Ralph
GR
Duke Clinical Research Institute, Durham, North Carolina 27715, USA. corey001@mc.duke.edu
Wilcox
Mark
M
Talbot
George H
GH
Friedland
H David
HD
Baculik
Tanya
T
Witherell
Gary W
GW
Critchley
Ian
I
Das
Anita F
AF
Thye
Dirk
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001398:Aztreonam / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017192:Skin Diseases, Bacterial / Q000188:drug therapy*; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D055815:Young Adult; D000097583:Ceftaroline
D000900:Anti-Bacterial Agents; D001398:Aztreonam; D002511:Cephalosporins; D014640:Vancomycin; D000097583:Ceftaroline