Objectives: This exploratory pooled analysis assessed the efficacy and safety of ceftaroline fosamil and comparators across six phase III clinical trials in adults with community-acquired pneumonia (CAP) or complicated skin and soft-tissue infection (cSSTI) and secondary bacteraemia. Methods: In each trial, FOCUS 1 and 2 (CAP), Asia CAP trial, CANVAS 1 and 2 (cSSTI) and COVERS (cSSTI), patients were randomised to ceftaroline fosamil [600 mg q12h by 1-h i.v. infusion, except in COVERS (600 mg q8h by 2-h i.v. infusion), adjusted for renal function] or comparator. Efficacy assessments included clinical and microbiological responses at test-of-cure visit [microbiological modified intent-to-treat (mMITT) population]. Safety outcomes were assessed. Results: The pooled mMITT population comprised 1976 patients, of whom 138 had baseline bacteraemia (ceftaroline fosamil, n = 72; comparator, n = 66). Predominant baseline blood pathogens were Staphylococcus aureus (n = 29), Streptococcus pneumoniae (n = 19) and other streptococci (n = 12). Clinical cure rates in bacteraemic patients were 55/72 (76.4%) and 51/66 (77.3%) for ceftaroline fosamil and comparators, respectively, and in non-bacteraemic patients were 822/966 (85.1%) and 717/872 (82.2%). Favourable microbiological response rates in bacteraemic patients were 56/72 (77.8%) for ceftaroline fosamil and 54/66 (81.8%) for comparators, and in non-bacteraemic patients were 825/966 (85.4%) and 719/872 (82.5%). Adverse events in bacteraemic patients were consistent with the known ceftaroline fosamil safety profile or the underlying indications. Conclusion: These pooled clinical and microbiological efficacy data demonstrate generally favourable outcomes for ceftaroline fosamil in patients with CAP or cSSTI and secondary bacteraemia.
Bibliographical noteFunding Information:
The authors thank the patients, their families and all investigators involved in the ceftaroline fosamil clinical trial programme. Medical writing support was provided by Mark Waterlow, BSc, CMPP, and Melanie More, BSc, CMPP (Prime, Knutsford, UK), funded by Pfizer. Ultimate responsibility for the opinions, conclusions and data interpretation lies with the authors.
Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices: (i) for indications that have been approved in the USA and/or EU; or (ii) in programmes that have been terminated (i.e. development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary and statistical analysis plan. Data may be requested from Pfizer trials 24?months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer. The authors thank the patients, their families and all investigators involved in the ceftaroline fosamil clinical trial programme. Medical writing support was provided by Mark Waterlow, BSc, CMPP, and Melanie More, BSc, CMPP (Prime, Knutsford, UK), funded by Pfizer. Ultimate responsibility for the opinions, conclusions and data interpretation lies with the authors. These analyses were conducted by Pfizer. The CANVAS 1 and 2 trials were sponsored by 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). MK, JLY, GGS and HL-T are employees of Pfizer Inc.; MW and MD received institutional research funding for the conduct of studies included in these analyses from the respective study sponsors [AstraZeneca for COVERS and AbbVie (formerly Allergan) for CANVAS 1 and CANVAS 2]; MW 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. This subset analysis was based on five previously reported phase III ceftazidime/avibactam clinical trials. Ethical approval and patient consent to participate were obtained for each of the previously reported trials, and all trials were conducted in accordance with the Declaration of Helsinki 1964 and its later amendments.
© 2021 The Authors
- Bloodstream infection
- Ceftaroline fosamil
- Community-acquired pneumonia
- Complicated skin and soft-tissue infection
- Secondary bacteraemia