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

Duke Clinical Research Institute, Durham, North Carolina 27715, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 09/2010; 51(6):641-50. DOI: 10.1086/655827
Source: PubMed


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.
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.
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.
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. identifiers: NCT00424190 for CANVAS 1 and NCT00423657 for CANVAS 2.

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Available from: Tanya O'Neal, Jun 24, 2015
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    • "The CANVAS (CeftAroliNe Versus vAncomycin in Skin and skin structure infections) 1 and 2 studies (NCT00424190 and NCT00423657, respectively) were multinational, multicenter, phase 3, double-masked, randomized, active comparator-controlled trials designed to evaluate the safety and efficacy of monotherapy with ceftaroline fosamil 600 mg IV every 12 h compared with a combination of vancomycin 1 g every 12 h plus aztreonam 1 g every 12 h IV for 5–14 days for the treatment of ABSSSI [14, 15, 45, 47] Dose adjustments for renal impairment by unblinded pharmacists were based on creatinine clearance and institutional guidelines. "
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    ABSTRACT: Ceftaroline is a novel cephalosporin with a favorable tolerability profile and broad in vitro activity against many resistant Gram-positive and common Gram-negative organisms. Ceftaroline fosamil is the first cephalosporin to be approved by the United States Food and Drug Administration (FDA) for the treatment of adults with acute bacterial skin and soft tissue infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It is also approved by the FDA for the treatment of adults with community-acquired bacterial pneumonia, including cases caused by Streptococcus pneumoniae (with or without concurrent bacteremia), although there are no data at this time to support the use of ceftaroline fosamil for the treatment of pneumonia caused by MRSA. Ceftaroline fosamil is likewise approved by the European Commission for the treatment of adults with complicated skin and soft tissue infections or community-acquired pneumonia. This review summarizes the pharmacokinetic and microbiologic properties of ceftaroline, as well as the safety and efficacy data that led to its approval by the FDA in 2010 and the European Commission in 2012. Future directions to be addressed are also highlighted.
    12/2013; 2(2):95-110. DOI:10.1007/s40121-013-0010-x
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    • "These findings compare favourably with the results from two double-blinded Phase III clinical studies (each with 700 patients) comparing ceftaroline fosamil with vancomycin±aztreonam in complicated ABSSSIs. An integrated analysis of the two studies showed comparable clinical cure rates of 92–95% for ceftaroline fosamil and the comparator.29 The overall success rate of 85% in CAPTURE is lower than those in the clinical studies and reflect differences in the study populations. "
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    ABSTRACT: The Clinical Assessment Program and TEFLARO Utilization Registry (CAPTURE) is a multicentre retrospective cohort study in the USA describing treatment of acute bacterial skin and skin structure infection (ABSSSI) with ceftaroline fosamil (CPT-F). Charts for review were chosen by random selection. Among 647 evaluable patients, 52% were obese, 46% had diabetes mellitus (DM), and 19% had peripheral vascular disease (PVD). Methicillin-resistant Staphylococcus aureus (MRSA) was recovered in 28% and methicillin-susceptible S. aureus (MSSA), 11%. Antibiotics were administered prior to CPT-F treatment in 80%, and concurrently in 39%. Clinical success overall was 85%; in patients with DM, 83%; with PVD, 76%; and in obese patients, 88%. Clinical success was ≥79% across all infection types; 81% for MRSA and 83% for MSSA; and 86% for ceftaroline monotherapy and 84% for concurrent therapy. These high clinical success rates support CPT-F as an effective treatment option for ABSSSI, including infections due to MRSA and patients with significant co-morbidities.
    Journal of chemotherapy (Florence, Italy) 09/2013; 25(6). DOI:10.1179/1973947813Y.0000000144 · 1.60 Impact Factor
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    • "Clinical trials have demonstrated that ceftaroline was non-inferior to the standard of care for the treatment of community-acquired pneumonia (CAP) and respectively for skin and soft structure infections (SSTI). [11,12]. Ceftaroline has been approved by FDA in 2010 and by European Medical Agency (EMA) in 2012 for the treatment of acute bacterial SSSIs and CAP. "
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    ABSTRACT: Bacterial resistance to antibiotics is growing up day by day in both community and hospital setting, with a significant impact on the mortality and morbidity rates and the financial burden that is associated. In the last two decades multi drug resistant microorganisms (both hospital- and community-acquired) challenged the scientific groups into developing new antimicrobial compounds that can provide safety in use according to the new regulation, good efficacy patterns, and low resistance profile. In this review we made an evaluation of present data regarding the new classes and the new molecules from already existing classes of antibiotics and the ongoing trends in antimicrobial development. Infectious Diseases Society of America (IDSA) supported a proGram, called "the [prime]10 x 20[prime] initiative", to develop ten new systemic antibacterial drugs within 2020. The microorganisms mainly involved in the resistance process, so called the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and enterobacteriaceae) were the main targets. In the era of antimicrobial resistance the new antimicrobial agents like fifth generation cephalosporins, carbapenems, monobactams, beta-lactamases inhibitors, aminoglycosides, quinolones, oxazolidones, glycopeptides, and tetracyclines active against Gram-positive pathogens, like vancomycin-resistant S. aureus (VRSA) and MRSA, penicillin-resistant streptococci, and vancomycin resistant Enterococcus (VRE) but also against highly resistant Gram-negative organisms are more than welcome. Of these compounds some are already approved by official agencies, some are still in study, but the need of new antibiotics still does not cover the increasing prevalence of antibiotic-resistant bacterial infections. Therefore the management of antimicrobial resistance should also include fostering coordinated actions by all stakeholders, creating policy guidance, support for surveillance and technical assistance.
    Annals of Clinical Microbiology and Antimicrobials 08/2013; 12(1):22. DOI:10.1186/1476-0711-12-22 · 2.19 Impact Factor
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