Introduction: In three phase III randomized controlled trials, ceftaroline fosamil was shown to be non-inferior to vancomycin plus aztreonam for the treatment of complicated skin and soft tissue infections (cSSTIs). This exploratory analysis evaluated the impact of underlying comorbidities on clinical outcomes in patients with cSSTI pooled from these three studies. Methods: CANVAS 1 and 2 and COVERS evaluated ceftaroline fosamil (600 mg every 12 h [q12h]; 600 mg every 8 h [q8h; COVERS]) versus vancomycin plus aztreonam (1 g q12h each [CANVAS 1 and 2]; vancomycin 15 mg/kg q12h and aztreonam 1 g q8h [COVERS]) in hospitalized adults with cSSTI. The primary efficacy variable in each trial was clinical response at the test-of-cure (TOC) visit. Subgroup analyses were performed on the pooled clinically evaluable (CE) population, exploring the impact of age and various baseline comorbidities. Results: Overall, 1808 patients were included in the CE population (1005 ceftaroline fosamil; 803 vancomycin plus aztreonam). Clinical cure rates at TOC were 89.7% (ceftaroline fosamil) and 90.8% (vancomycin plus aztreonam) (difference [95% confidence interval] − 1.13 [− 3.87, 1.67]). Clinical response rates were similar between treatment groups, regardless of age (≤ 65 years or > 65 years), and in subgroups of patients with and without diabetes mellitus, peripheral vascular disease, cancer/malignancy, renal impairment, and obesity; within these subgroups, efficacy and safety results were generally consistent with those of the overall cSSTI population. Conclusions: This analysis provides supportive evidence of the efficacy of ceftaroline fosamil in patients with cSSTI and underlying comorbidities. Trial Registration: CANVAS 1, NCT00424190 and CANVAS 2, NCT00423657 (both trials first posted on ClinicalTrials.gov 18/01/2007); COVERS, NCT01499277 (first posted on ClinicalTrials.gov 26/12/2011).
Bibliographical noteFunding Information:
Jean Li Yan, Gregory G. Stone, and Michal Kantecki are employees of and shareholders in Pfizer. Pedro L. Gonzalez is a former employee of AbbVie, and is currently an employee of BD. Mark Wilcox and Matthew Dryden received institutional research funding for the conduct of studies included in these analyses from the respective study sponsors. Mark Wilcox has received consulting fees from AiCuris, AstraZeneca, Bayer, Cerexa, Durata, The Medicines Company, Menarini, Motif Biosciences, Nabriva, Paratek, and Pfizer; lecture fees from AbbVie, AstraZeneca, and Pfizer; and grant support from Motif Biosciences, Nabriva, Paratek, Pfizer, Qpex Biopharma, and VenatoRx.
The CANVAS 1 and 2 trials were sponsored by Forest Laboratories, a subsidiary of AbbVie (following its acquisition of Allergan). The COVERS trial was originally sponsored by AstraZeneca and is now sponsored by Pfizer. AstraZeneca's rights to ceftaroline fosamil were acquired by Pfizer in December 2016. Ceftaroline fosamil is being developed by Pfizer and AbbVie (following its acquisition of Allergan). Funding for the journal’s Rapid Service Fee was provided by Pfizer.
© 2021, The Author(s).
- Ceftaroline fosamil
- Complicated skin and soft tissue infection