FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia

File Jr., Thomas M. and Low, Donald E. and Eckburg, Paul B. and Talbot, George H. and Friedland, H. David and Lee, Jon and Llorens, Lily and Critchley, Ian A. and Thye, Dirk A. and on behalf of the FOCUS 1 investigators, : and Pertseva, Tetiana and Rodionova, Victoria and Yefimov, Volodymyr (2011) FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. Journal of Antimicrobial Chemotherapy, 66 (3). iii19-iii32. ISSN 0305-7453 (Print), 1460-2091 (Online)

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Abstract

Objectives: Ceftaroline, the active form of the prodrug ceftaroline fosamil, is a novel cephalosporin with bactericidal activity against important pathogens associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and common Gram-negative pathogens. FOCUS 1 is a randomized, double-blinded, Phase III study that was conducted to evaluate the efficacy and safety of ceftaroline fosamil in treating patients with CAP. The primary objective was to determine non-inferiority [lower limit of 95% confidence interval (CI) ≥ 210%] in clinical cure rates achieved with ceftaroline fosamil compared with those achieved with ceftriaxone in the clinically evaluable (CE) and modified intent-to-treat efficacy (MITTE) populations. Methods: Patients hospitalized in a non-intensive care unit setting with CAP of Pneumonia Outcomes Research Team (PORT) risk class III or IV requiring intravenous (iv) therapy were randomized (1:1) to receive 600 mg of ceftaroline fosamil iv every 12 h or 1 g of ceftriaxone iv every 24 h. Patients also received two 500 mg doses of oral clarithromycin every 12 h administered on day 1. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 1 registration number NCT00621504 (http://clinicaltrials.gov/ ct2/show/NCT00621504). Results: Of 613 enrolled patients, 298 received ceftaroline fosamil and 308 received ceftriaxone. Baseline characteristics between treatment groups were comparable. Clinical cure rates were as follows: CE population, 86.6% (194/224) for ceftaroline fosamil and 78.2% (183/234) for ceftriaxone [difference (95% CI), 8.4% (1.4, 15.4)]; and MITTE population, 83.8% (244/291) for ceftaroline fosamil and 77.7% (233/300) for ceftriaxone [difference (95% CI), 6.2% (20.2, 12.6)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE population were 88.9% (24/27) and 66.7% (20/30) for ceftaroline fosamil and ceftriaxone, respectively. Both agents were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations because of an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, insomnia and nausea, and the most common AEs for ceftriaxone-treated patients were hypokalaemia, hypertension, nausea and diarrhoea. Conclusions: Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORTrisk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.

Item Type:	Article
Additional Information:	Идентификационный номер: WOS:000290153500004 Идентификатор PubMed: 21482566 Tetiana Tetiana Pertseva, Dnipropetrovsk State Medical Academy, City Hospital #6, Dnipropetrovsk, Ukraine; Volodymyr Yefimov, L.T. Mala Therapeutics Institute under the Ukrainian Academy of Medical Sciences, Kharkiv, Ukraine; Volodymyr Havrysyuk, F.H. Yanovskyi Phthisiology and Pulmonology Institute under the Ukrainian Academy of Medical Sciences, Kyiv, Ukraine; Vasyl Melnyk, Kyiv City Tuberculosis Hospital #1, Kyiv, Ukraine; Lyudmyla Yashyna, F.H. Yanovskyi Phthisiology and Pulmonology Institute under the Ukrainian Academy of Medical Sciences, Kyiv, Ukraine; Nadiya Monogarova, M. Horky Donetsk State Medical University; Donetsk Regional Community-Based Medical Association, Donetsk, Ukraine; Yuriy Kolchyn, Luhansk State Medical University, Luhansk Regional Hospital, Luhansk, Ukraine; Roman Dutka, Lviv Danyla Halytskyi National Medical University, Public City Clinical Hospital #5, Lviv, Ukraine; Oleksandr Smolyanyi, Odesa Regional Clinical Hospital, Odesa, Ukraine; Nadiya Tryshchuk, Kharkiv Medical Academy for Postgraduate Education, O.I. Meschaninova City Clinical Hospital of Emergency and Intensive Care, Kharkiv, Ukraine; Igor Kaydashev, Ukraine Medical Stomatological Academy, Clinical Facility: City Hospital #1, Poltava, Ukraine; Victoria Rodionova, Dnipropetrovsk State Medical Academy, City General Clinical Hospital #4, Dnipropetrovsk, Ukraine; Vasyl Neyko, Ivano-Frankivsk State Medical University, Central City Clinical Hospital, Ivano-Frankivsk, Ukraine; Ivan Chopey, Uzhgorod National University, Uzhgorod Railway Station Clinical Hospital, Uzhgorod, Ukraine;
Uncontrolled Keywords:	CAP, CABP, Streptococcus pneumoniae, antimicrobial therapy
Subjects:	Clinical Pharmacology Pulmonology Microbiology
Divisions:	Departments > Department of Internal Medicine 1 (formerly - Faculty Therapy and Endocrinology)
Depositing User:	Елена Шрамко
Date Deposited:	14 May 2021 15:40
Last Modified:	14 May 2021 15:40
URI:	http://repo.dma.dp.ua/id/eprint/6505

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