CANVAS 1 and 2: analysis of clinical response at day 3 in two phase 3 trials of ceftaroline fosamil versus vancomycin plus aztreonam in treatment of acute bacterial skin and skin structure infections.
Scientific and regulatory interest in assessing clinical endpoints after 48 to 72 h of treatment for acute bacterial skin and skin structure infections (ABSSSI) has increased. Historical, pre-antibiotic-era data suggest that a treatment effect relative to untreated controls can be discerned in this time interval. Ceftaroline fosamil, a broad-spectrum bactericidal cephalosporin with activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative organisms was efficacious in two phase 3 trials of complicated skin infections (CANVAS 1 and 2) using clinical cure rates at the test-of-cure visit. To assess an early clinical response in the CANVAS trials, a retrospective analysis using a day 3 clinical endpoint was conducted. Adults with ABSSSI received intravenous ceftaroline fosamil at 600 mg every 12 h (q12h) or vancomycin at 1 g plus aztreonam at 1 g (V/A) q12h for 5 to 14 days. Clinical response at day 3, defined as cessation of infection spread and absence of fever, was analyzed in patients with a lesion size of ≥ 75 cm(2) and either deep and/or extensive cellulitis, major abscess, or an infected wound. Day 3 integrated CANVAS clinical response rates were 74.0% (296/400) for ceftaroline and 66.2% (263/397) for V/A (difference, 7.8%; 95% confidence interval [CI], 1.3% to 14.0%). In the individual studies, absolute treatment differences of 9.4% (CANVAS 1) and 5.9% (CANVAS 2) favoring ceftaroline were observed. For ABSSSI due to MRSA, response rates were 81.7% and 77.4% in the ceftaroline and V/A groups, respectively. In this retrospective analysis, ceftaroline fosamil monotherapy had a numerically higher clinical response than V/A at day 3 in the treatment of ABSSSI.
Cerexa, Inc, Oakland, California, USA. dfriedland@cerexa.com
H David
HD
Friedland
Tanya
T
O'Neal
Donald
D
Biek
Paul B
PB
Eckburg
Douglas R
DR
Rank
Lily
L
Llorens
Alex
A
Smith
Gary W
GW
Witherell
Joseph B
JB
Laudano
Dirk
D
Thye
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001398:Aztreonam / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis*; D002511:Cephalosporins / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D012189:Retrospective Studies; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use*; D000097583:Ceftaroline
D000900:Anti-Bacterial Agents; D001398:Aztreonam; D015415:Biomarkers; D002511:Cephalosporins; D014640:Vancomycin; D000097583:Ceftaroline