Comparative Study of Ceftaroline vs. Ceftriaxone in Adult Subjects With Community-Acquired Pneumonia (CAP)

A Phase 3, Multicenter, Randomized, Double-blind, Comparative Study to Evaluate the Safety and Efficacy of Ceftaroline Versus Ceftriaxone, With Adjunctive Clarithromycin, in the Treatment of Adult Subjects With Community-Acquired Pneumonia

The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of Community-Acquired Pneumonia

Study Overview

• Status: Completed
• Conditions: Bacterial Pneumonia
• Intervention / Treatment: Drug: Placebo; Drug: Ceftaroline fosamil for Injection; Drug: Clarithromycin; Drug: IV Ceftriaxone

Detailed Description

The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of Community-Acquired Pneumonia. Clinical trials for this study is held in many countries

• Study Type: Interventional
• Enrollment (Actual): 606
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1650
    • Investigational Site
  • Buenos Aires, Argentina, 1748
    • Investigational Site
  • Buenos Aires, Argentina, B1702FWM
    • Investigational Site
  • Buenos Aires, Argentina, B6700AQJ
    • Investigational Site
  • Buenos Aires, Argentina, C1155ADP
    • Investigational Site
  • Buenos Aires, Argentina, C1430BKC
    • Investigational Site
  • Buenos Aires, Argentina, C1437 BZK
    • Investigational Site
  • Vicente Lopez, Argentina, 1602
    • Investigational Site
  • C.a.b.a.
    • Buenos Aires, C.a.b.a., Argentina, C1431FWO
      • Investigational Site
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, T4000IIH
      • Investigational Site
• Austria
  • Vienna, Austria, A-1090
    • Investigational Site
  • Wien, Austria, A-1030
    • Investigational Site
• Brazil
  • Belo Horizonte, Brazil, 30140-062
    • Investigational site 2
  • Belo Horizonte MG, Brazil, 30150-221
    • Investigational site 1
  • Campinas, Brazil, SP 13059-900
    • Investigational Site
  • Curitiba-PR, Brazil, 80810-040
    • Investigational Site
  • Juiz de Fora, Brazil, 36036-110
    • Investigational Site
  • Porto Alegre, Brazil, 90035-001
    • Investigational Site
  • Sao Paolo, Brazil, 04038-905
    • Investigational Site
  • Sao Paolo, Brazil, 17201-340
    • Investigational Site
  • G.o.
    • Goiania, G.o., Brazil, 74465-539
      • Investigational Site
  • RS
    • Porto Alegre, RS, Brazil, 90020-090
      • Investigational Site
    • Porto Alegre, RS, Brazil, 90610-001
      • Investigational Site
  • SP
    • Sao Jose do Rio Preto, SP, Brazil, 15090-000
      • Investigational Site
• Bulgaria
  • Burgas, Bulgaria, 8000
    • Investigational Site
  • Sofia, Bulgaria, 1431
    • Investigational Site
  • Varna, Bulgaria, 9010
    • Investigational Site
• Estonia
  • Tallinn, Estonia, 10138
    • Investigational Site
  • Tallinn, Estonia, 13419
    • Investigational Site
  • Tartu, Estonia, 51014
    • Investigational Site
• France
  • Annecy, France, 74000
    • Investigational Site
  • Argenteuil, France, 95100
    • Investigational Site
  • Paris, France, 750120
    • Investigational Site
  • Paris, France, 75475
    • Investigational Site
  • Paris, France, 75674
    • Investigational Site
• Georgia
  • Tbilisi, Georgia, 0144
    • Investigational Site
  • Tbilisi, Georgia, 0160
    • Investigational Site
• Germany
  • Berlin, Germany, 13353
    • Investigational Site
  • Bochum, Germany, 44793
    • Investigational Site
  • Bochum, Germany, 44879
    • Investigational Site
  • Erfurt, Germany, 99089
    • Investigational Site
  • Heppenheim, Germany, 64646
    • Investigational Site
  • Lich, Germany, 53545
    • Investigational Site
  • Lubeck, Germany, 23538
    • Investigational Site
  • Luedenscheid, Germany, 58515
    • Investigational Site
  • Paderborn, Germany, 33098
    • Investigational Site
  • Schkeuditz, Germany, 04435
    • Investigational Site
  • Ulm, Germany, 89081
    • Investigational Site
  • Wiesbaden, Germany, 65199
    • Investigational Site
  • Berlin
    • Lindenberger, Berlin, Germany, 13125
      • Investigational Site
• Hungary
  • Budapest, Hungary, 1125
    • Investigational Site
  • Matrahaza, Hungary, 3233
    • Investigational Site
  • Miskolc, Hungary, 3529
    • Investigational Site
  • Pecs, Hungary, 7623
    • Investigational Site
  • Sopron, Hungary, 9400
    • Investigational Site
  • Tatabanya, Hungary, 2800
    • Investigational Site
  • Torokbalint, Hungary, 2045
    • Investigational Site
  • Szanatorium
    • Tatabanya, Szanatorium, Hungary, 2800
      • Investigational Site
• India
  • Tamilnadu
    • Vellore, Tamilnadu, India, 632004
      • Investigational Site
• Lithuania
  • Kaunas, Lithuania, LT-45130
    • Investigational Site
  • Kaunas, Lithuania, LT-50009
    • Investigational Site
  • Klaipeda, Lithuania, LT-92231
    • Investigational Site
  • Klaipeda, Lithuania, LT-92288
    • Investigational Site
  • Siauliai, Lithuania, LT-76231
    • Investigational Site
  • Vilnius, Lithuania, LT-10207
    • Investigational Site
• Malaysia
  • Kedah, Malaysia, 05460
    • Investigational Site
  • Kuala Lumpur, Malaysia, 50590
    • Investigational Site
  • Johor
    • Johor Bahru, Johor, Malaysia, 80100
      • Investigational Site
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 05460
      • Inestigational Site
  • Penang
    • Georgetown, Penang, Malaysia, 10990
      • Investigational Site
• Poland
  • Bedzin, Poland, 42-500
    • Investigational Site
  • Brzesku, Poland, 32-800
    • Investigational Site
  • Bytom, Poland, 41-902
    • Investigational Site
  • Chodziez, Poland, 64-800
    • Investigational Site
  • Czestochowa, Poland, 42-200
    • Investigational Site
  • Katowice-Ochojec, Poland, 40-635
    • Investigational Site
  • Krakow, Poland, 30-053
    • Investigational Site
  • Lublin, Poland, 20-178
    • Investigational Site
  • Lublin, Poland, 20-718
    • Investigational Site
  • Poznan, Poland, 60-569
    • Investigational Site
  • Poznan, Poland, 60-479
    • Investigational Site
  • Tychy, Poland, 43-100
    • Investigational Site
  • Warszawa, Poland, 01-138
    • Investigational Site
  • Warszawa, Poland, 03-401
    • Investigational Site
  • Warszawa, Poland, 03-737
    • Investigational Site
  • Warszawa, Poland, 127 02-507
    • Investigational Site
  • Wroclaw, Poland, 53-439
    • Investigational Site
• Romania
  • Bucharest, Romania, 050098
    • Investigational Site
  • Bucharest, Romania, 042122
    • Inestigational Site
  • Cluj Napoca, Romania, 400238
    • Investigational Site
  • Constanta, Romania
    • Investigational Site
  • Oradea, Romania, 410176
    • Investigational Site
  • St. Brasov, Romania, 25-27
    • Investigational Site
  • Targu Mures, Romania, 540136
    • Investigational Site
  • Timisoara, Romania
    • Investigational Site
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Investigational Site
  • Moscow, Russian Federation, 123182
    • Investigational Site
  • Moscow, Russian Federation, 119048
    • Investigational Site
  • Moscow, Russian Federation, 125206
    • Investigational Site
  • Rostov-on-Don, Russian Federation, 344010
    • Investigational Site
  • Saratov, Russian Federation, 410-002
    • Investigational Site
  • St Petersburg, Russian Federation, 194354
    • Investigational Site
  • St. Petersburg, Russian Federation, 191104
    • Investigational Site
  • St. Petersburg, Russian Federation, 195257
    • Investigational Site
  • Tatarstan, Russian Federation, 420-101
    • Investigational Site
  • Yekaterinburg, Russian Federation, 620109
    • Investigational Site
  • Yekaterinburg, Russian Federation, 620137
    • Investigational Site
  • Republic of Karelia
    • Petrozavodsk, Republic of Karelia, Russian Federation, 185014
      • Investigational Site
• Serbia
  • Belgrade, Serbia, 11080
    • Investigational Site
  • Knez Selo, Serbia, 18204
    • Investigational Site
  • Kragujevac, Serbia, 34000
    • Investigational Site
• Slovakia
  • Bratislava, Slovakia, 813 69
    • Investigational Site
  • Nitra-Zobor, Slovakia, 948 88
    • Slovakia
• South Africa
  • Benomi, South Africa, 1500
    • Investigational Site
  • Cape Town, South Africa, 7505
    • Investigational Site
  • Cape Town, South Africa, 7530
    • Investigational Site
  • Krugersdorp, South Africa, 1752
    • Investigational Site
  • Port Elizabeth, South Africa, 6020
    • Investigational Site
  • Pretoria, South Africa, 0001
    • Investigational Site
  • Pretoria, South Africa, 0084
    • Investigational Site
  • Pretoria, South Africa, 0140
    • Investigational Site
  • Pretoria, South Africa, 0188
    • Investigational Site
  • Somerset West, South Africa, 7130
    • Investigational Site
  • Worcester, South Africa, 6850
    • Investigational Site
  • Capetown
    • Bellville, Capetown, South Africa, 7530
      • Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • Investigational Site
  • Barcelona, Spain, 08036
    • Investigational Site
  • Elche, Spain, 03203
    • Investigational Site
  • Leon, Spain, 24411
    • Investigational Site
  • Madrid, Spain, 28007
    • Investigational Site
  • Valencia, Spain, 46009
    • Investigational Site
  • Vizcaya, Spain, 48960
    • Investigational Site
• Switzerland
  • Biel, Switzerland, 2501
    • Investigational Site
  • Geneve, Switzerland, 1211
    • Investigational Site
  • La Chaux-de-Fonds, Switzerland, 2300
    • Investigational Site
  • Lugano, Switzerland, 46,6903
    • Investigational Site
• Thailand
  • Bangkok, Thailand, 10110
    • Investigational Site
  • Bangkok, Thailand, 10400
    • Investigational Site
  • Bangkok, Thailand, 10400
    • InvestigationalSite
  • Bangkok, Thailand, 10700
    • Investigational Site
  • Chiang Mai, Thailand, 50200
    • Investigational Site
  • Khonkaen, Thailand, 40002
    • Investigational Site
  • Nonthaburi, Thailand, 11000
    • Investigational Site
• Ukraine
  • Aviv, Ukraine, 79013
    • Investigational Site
  • Dnipropetrovsk, Ukraine, 49074
    • Investigational Site
  • Dnipropetrovsk, Ukraine, 49102
    • Investigational Site
  • Donetsk, Ukraine, 83099
    • Investigational Site
  • Ivano-Frankivsk, Ukraine, 76025
    • Investigational Site
  • Kharkiv, Ukraine, 61018
    • Investigational Site
  • Kharkiv, Ukraine, 61035
    • Investigational Site
  • Kyiv, Ukraine, 03680
    • Investigational Site
  • Kyiv, Ukraine, 02091
    • Inestigational Site
  • Lugansk, Ukraine, 91045
    • Investigational Site
  • Odesa, Ukraine, 65025
    • Investigational Site
  • Poltava, Ukraine, 36038
    • Investigational Site
  • Uzhorod, Ukraine, 88015
    • Investigational Site
• United States
  • California
    • Los Angeles, California, United States, 90015
      • Investigational Site
    • Pasadena, California, United States, 91105
      • Investigational Site
    • Sacramento, California, United States, 95817
      • Investigational Site
    • San Diego, California, United States, 92114
      • Investigational Site
  • Florida
    • Orlando, Florida, United States, 32806
      • Investigational Site
  • Georgia
    • Fort Gordon, Georgia, United States, 30905
      • Investigational Site
  • Illinois
    • Peoria, Illinois, United States, 61603
      • Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422
      • Investigational Site
  • Montana
    • Butte, Montana, United States, 59701
      • Investigational Site
  • Ohio
    • Akron, Ohio, United States, 44305
      • Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects are required to meet the following inclusion criteria:

• Community-acquired pneumonia
• initial hospitalization, or treatment in an emergency room or urgent care setting
• infection would require initial treatment with IV antimicrobials.

Exclusion Criteria:

Subjects must NOT meet any of the following exclusion criteria:

• CAP suitable for outpatient therapy with an oral antimicrobial agent
• respiratory tract infections not due to community-acquired bacterial
• Non-infectious causes of pulmonary infiltrates
• Pleural empyema
• Infection with an atypical organism
• History of any hypersensitivity or allergic reaction to any ß-lactam antimicrobial
• History of any hypersensitivity or allergic reaction to clarithromycin or any macrolide/ ketolide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceftaroline fosamil for Injection; Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h). In both treatment groups, two doses of oral clarithromycin (500 mg q12h), defined as adjunctive therapy, were initiated on Study Day 1 with study drug therapy in order to provide an immunomodulatory benefit and initial therapy for possible infection due to an atypical organism.	Drug: Ceftaroline fosamil for Injection; 2 consecutive, 300 mg dose parenteral infused over 30 minutes, every 12 hours, for 5 to 7 days; Drug: Clarithromycin; In both treatment groups, two doses of oral clarithromycin (500 mg q12h), defined as adjunctive therapy, were initiated on Study Day 1 with study drug therapy in order to provide an immunomodulatory benefit and initial therapy for possible infection due to an atypical organism.
Active Comparator: IV Ceftriaxone; Ceftriaxone was administered as a 1-g IV infusion over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h). In both treatment groups, two doses of oral clarithromycin (500 mg q12h), defined as adjunctive therapy, were initiated on Study Day 1 with study drug therapy in order to provide an immunomodulatory benefit and initial therapy for possible infection due to an atypical organism.	Drug: Placebo; Subjects randomized to receive ceftriaxone will receive ceftriaxone at a dose of 1 g infused over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h). Twelve hours after each dose of ceftriaxone and saline placebo (ie, between ceftriaxone doses), subjects in this group will receive two consecutive saline placebo infusions, each infused over 30 minutes q24h. The ceftriaxone and saline placebo infusions will correspond to the q12h infusions of ceftaroline, thereby maintaining the blind; Drug: Clarithromycin; In both treatment groups, two doses of oral clarithromycin (500 mg q12h), defined as adjunctive therapy, were initiated on Study Day 1 with study drug therapy in order to provide an immunomodulatory benefit and initial therapy for possible infection due to an atypical organism.; Drug: IV Ceftriaxone; 1 g dose parenteral infused over 30 minutes, every 24 hours, for 5 to 7 days; Other Names: Ceftriaxone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations	Cure:Total resolution of all signs and symptoms of pneumonia (ie,CABP), or improvement to such an extent that further antimicrobial therapy was not necessary Failure: Any of the following: Persistence, incomplete clinical resolution, or worsening in signs and symptoms of CABP that required alternative antimicrobial therapy; Treatment-limiting adverse event (AE) leading to discontinuation of study drug therapy, when subject required alternative antimicrobial therapy to treat the pneumonia; Death wherein pneumonia (ie,CABP) was considered causative Indeterminate: Inability to determine an outcome	8 to 15 days after last dose of study drug
Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test-of-Cure (TOC) in the Clinically Evaluable (CE) Population		8-15 days after last dose of study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical Response at End of Therapy (EOT)	Last day of study drug administration
Clinical and Microbiological Response by Pathogen at TOC	8-15 days after last dose of study drug
Evaluate Safety	first dose, throughout the treatment period, and up to the TOC visit
Microbiological Success Rate at Test of Cure (TOC)	8-15 days after last dose of study drug
Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC)	8-15 days after last day of study drug
Clinical Relapse at Late Follow Up (LFU)	21-35 days after last dose of study drug
Microbiological Re-infection/Recurrence at LFU	21 to 35 days after last dose of study drug

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Investigators: Study Director: Thomas M File, MD, MS, SUMMA Health System

Publications and helpful links

General Publications

• Dryden M, Kantecki M, Yan JL, Stone GG, Leister-Tebbe H, Wilcox M. Treatment outcomes of secondary bacteraemia in patients treated with ceftaroline fosamil: pooled results from six phase III clinical trials. J Glob Antimicrob Resist. 2022 Mar;28:108-114. doi: 10.1016/j.jgar.2021.10.027. Epub 2021 Dec 16.
• Cheng K, Pypstra R, Yan JL, Hammond J. Summary of the safety and tolerability of two treatment regimens of ceftaroline fosamil: 600 mg every 8 h versus 600 mg every 12 h. J Antimicrob Chemother. 2019 Apr 1;74(4):1086-1091. doi: 10.1093/jac/dky519.
• Taboada M, Melnick D, Iaconis JP, Sun F, Zhong NS, File TM, Llorens L, Friedland HD, Wilson D. Ceftaroline fosamil versus ceftriaxone for the treatment of community-acquired pneumonia: individual patient data meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2016 Apr;71(4):862-70. doi: 10.1093/jac/dkv415. Epub 2015 Dec 24. Erratum In: J Antimicrob Chemother. 2016 Jun;71(6):1748-9.
• Lodise TP, Anzueto AR, Weber DJ, Shorr AF, Yang M, Smith A, Zhao Q, Huang X, File TM. Assessment of time to clinical response, a proxy for discharge readiness, among hospitalized patients with community-acquired pneumonia who received either ceftaroline fosamil or ceftriaxone in two phase III FOCUS trials. Antimicrob Agents Chemother. 2015 Feb;59(2):1119-26. doi: 10.1128/AAC.03643-14. Epub 2014 Dec 8.
• Shorr AF, Kollef M, Eckburg PB, Llorens L, Friedland HD. Assessment of ceftaroline fosamil in the treatment of community-acquired bacterial pneumonia due to Streptococcus pneumoniae: insights from two randomized trials. Diagn Microbiol Infect Dis. 2013 Mar;75(3):298-303. doi: 10.1016/j.diagmicrobio.2012.12.002. Epub 2013 Jan 26.
• Rank DR, Friedland HD, Laudano JB. Integrated safety summary of FOCUS 1 and FOCUS 2 trials: Phase III randomized, double-blind studies evaluating ceftaroline fosamil for the treatment of patients with community-acquired pneumonia. J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii53-9. doi: 10.1093/jac/dkr099.
• File TM Jr, Low DE, Eckburg PB, Talbot GH, Friedland HD, Lee J, Llorens L, Critchley IA, Thye DA; FOCUS 1 investigators. FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii19-32. doi: 10.1093/jac/dkr096.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: February 11, 2008
• First Submitted That Met QC Criteria: February 20, 2008
• First Posted (Estimate): February 22, 2008

Study Record Updates

• Last Update Posted (Actual): March 14, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: antibiotic; CAP; bacteria; Ceftriaxone; Streptococcus pneumoniae; antimicrobial resistance; beta-lactam; ceftaroline; Community-acquired pneumonia; Haemophilus influenzae; Mycoplasma pneumoniae; Chlamydophila spp; pneumococci; IV (intravenous); Legionella spp; Multi-drug resistant Streptococcus pneumoniae (MDRSP); ß-lactam
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia; Pneumonia, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Ceftriaxone; Clarithromycin; Ceftaroline fosamil
• Other Study ID Numbers: P903-08