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

NCT00621504 | Completed Phase 3 Results

• 1 other identifier: P903-08
• Study Type: interventional
• Target: 606
• Locations: 22 countries
• Sites: 165

Brief Summary

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

Conditions

Bacterial Pneumonia

Keywords

ceftaroline; Community-acquired pneumonia; CAP; IV (intravenous); Streptococcus pneumoniae; Haemophilus influenzae; Mycoplasma pneumoniae; Chlamydophila spp; Legionella spp; Multi-drug resistant Streptococcus pneumoniae (MDRSP); antimicrobial resistance; pneumococci; Ceftriaxone; bacteria; ß-lactam; beta-lactam; antibiotic

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Clinical Response at End of Therapy (EOT)

  Last day of study drug administration

• 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 and Microbiological Response by Pathogen at TOC

  8-15 days after last dose of study drug

• Clinical Relapse at Late Follow Up (LFU)

  21-35 days after last dose of study drug

Study Arms (2)

Ceftaroline fosamil for Injection

EXPERIMENTAL

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; Drug: Clarithromycin

IV Ceftriaxone

ACTIVE COMPARATOR

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: IV Ceftriaxone; Drug: Placebo; Drug: Clarithromycin

Interventions

Ceftaroline fosamil for Injection DRUG

2 consecutive, 300 mg dose parenteral infused over 30 minutes, every 12 hours, for 5 to 7 days

Ceftaroline fosamil for Injection

IV Ceftriaxone DRUG

1 g dose parenteral infused over 30 minutes, every 24 hours, for 5 to 7 days

Also known as: Ceftriaxone

IV Ceftriaxone

Placebo DRUG

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

IV Ceftriaxone

Clarithromycin DRUG

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.

Ceftaroline fosamil for Injection; IV Ceftriaxone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Forest Laboratories: lead

Study Sites (168)

Investigational site

Los Angeles, California, 90015, United States

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Pasadena, California, 91105, United States

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Sacramento, California, 95817, United States

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San Diego, California, 92114, United States

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Orlando, Florida, 32806, United States

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Fort Gordon, Georgia, 30905, United States

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Peoria, Illinois, 61603, United States

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Baltimore, Maryland, 21237, United States

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Minneapolis, Minnesota, 55422, United States

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Butte, Montana, 59701, United States

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Akron, Ohio, 44305, United States

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Houston, Texas, 77030, United States

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Buenos Aires, C.a.b.a., C1431FWO, Argentina

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San Miguel de Tucumán, Tucumán Province, T4000IIH, Argentina

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Buenos Aires, 1650, Argentina

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Buenos Aires, 1748, Argentina

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Buenos Aires, B1702FWM, Argentina

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Buenos Aires, B6700AQJ, Argentina

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Buenos Aires, C1155ADP, Argentina

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Buenos Aires, C1430BKC, Argentina

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Buenos Aires, C1437 BZK, Argentina

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Vicente López, 1602, Argentina

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Vienna, A-1030, Austria

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Vienna, A-1090, Austria

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Goiânia, G.o., 74465-539, Brazil

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Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

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Porto Alegre, Rio Grande do Sul, 90610-001, Brazil

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São José do Rio Preto, São Paulo, 15090-000, Brazil

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Belo Horizonte, 30140-062, Brazil

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Belo Horizonte MG, 30150-221, Brazil

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Campinas, SP 13059-900, Brazil

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Curitiba-PR, 80810-040, Brazil

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Juiz de Fora, 36036-110, Brazil

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Porto Alegre, 90035-001, Brazil

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São Paulo, 04038-905, Brazil

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São Paulo, 17201-340, Brazil

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Burgas, 8000, Bulgaria

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Sofia, 1431, Bulgaria

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Varna, 9010, Bulgaria

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Tallinn, 10138, Estonia

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Tallinn, 13419, Estonia

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Tartu, 51014, Estonia

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Annecy, 74000, France

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Argenteuil, 95100, France

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Paris, 750120, France

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Paris, 75475, France

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Paris, 75674, France

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Tbilisi, 0144, Georgia

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Tbilisi, 0160, Georgia

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Lindenberger, State of Berlin, 13125, Germany

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Berlin, 13353, Germany

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Bochum, 44793, Germany

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Bochum, 44879, Germany

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Erfurt, 99089, Germany

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Heppenheim an der Bergstrasse, 64646, Germany

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Lich, 53545, Germany

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Lübeck, 23538, Germany

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Lüdenscheid, 58515, Germany

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Paderborn, 33098, Germany

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Schkeuditz, 04435, Germany

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Ulm, 89081, Germany

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Wiesbaden, 65199, Germany

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Tatabánya, Szanatorium, 2800, Hungary

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Budapest, 1125, Hungary

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Mátraháza, 3233, Hungary

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Miskolc, 3529, Hungary

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Pécs, 7623, Hungary

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Sopron, 9400, Hungary

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Tatabánya, 2800, Hungary

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Törökbálint, 2045, Hungary

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Vellore, Tamil Nadu, 632004, India

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Kaunas, LT-45130, Lithuania

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Kaunas, LT-50009, Lithuania

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Klaipėda, LT-92231, Lithuania

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Klaipėda, LT-92288, Lithuania

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Šiauliai, LT-76231, Lithuania

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Vilnius, LT-10207, Lithuania

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Johor Bahru, Johor, 80100, Malaysia

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Cheras, Kuala Lumpur, 05460, Malaysia

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George Town, Pulau Pinang, 10990, Malaysia

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Kedah, 05460, Malaysia

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Kuala Lumpur, 50590, Malaysia

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Będzin, 42-500, Poland

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Brzesku, 32-800, Poland

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Bytom, 41-902, Poland

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Chodzież, 64-800, Poland

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Częstochowa, 42-200, Poland

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Katowice-Ochojec, 40-635, Poland

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Krakow, 30-053, Poland

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Lublin, 20-178, Poland

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Lublin, 20-718, Poland

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Poznan, 60-479, Poland

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Poznan, 60-569, Poland

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Tychy, 43-100, Poland

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Warsaw, 01-138, Poland

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Warsaw, 03-401, Poland

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Warsaw, 03-737, Poland

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Warsaw, 127 02-507, Poland

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Wroclaw, 53-439, Poland

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Bucharest, 042122, Romania

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Bucharest, 050098, Romania

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Cluj-Napoca, 400238, Romania

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Constanța, Romania

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Oradea, 410176, Romania

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Saint Brasov, 25-27, Romania

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Târgu Mureş, 540136, Romania

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Timișoara, Romania

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Petrozavodsk, Republic of Karelia, 185014, Russia

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Arkhangelsk, 163045, Russia

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Moscow, 119048, Russia

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Moscow, 123182, Russia

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Moscow, 125206, Russia

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Rostov-on-Don, 344010, Russia

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Saint Petersburg, 191104, Russia

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Saint Petersburg, 194354, Russia

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Saint Petersburg, 195257, Russia

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Saratov, 410-002, Russia

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Tatarstan, 420-101, Russia

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Yekaterinburg, 620109, Russia

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Yekaterinburg, 620137, Russia

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Belgrade, 11080, Serbia

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Knez-Selo, 18204, Serbia

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Kragujevac, 34000, Serbia

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Bratislava, 813 69, Slovakia

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Slovakia

Nitra-Zobor, 948 88, Slovakia

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Bellville, Capetown, 7530, South Africa

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Benomi, 1500, South Africa

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Cape Town, 7505, South Africa

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Cape Town, 7530, South Africa

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Krugersdorp, 1752, South Africa

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Port Elizabeth, 6020, South Africa

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Pretoria, 0001, South Africa

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Pretoria, 0084, South Africa

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Pretoria, 0140, South Africa

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Pretoria, 0188, South Africa

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Somerset West, 7130, South Africa

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Worcester, 6850, South Africa

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Elche, 03203, Spain

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León, 24411, Spain

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Madrid, 28007, Spain

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Valencia, 46009, Spain

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Vizcaya, 48960, Spain

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Biel, 2501, Switzerland

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Geneva, 1211, Switzerland

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La Chaux-de-Fonds, 2300, Switzerland

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Lugano, 46,6903, Switzerland

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Bangkok, 10110, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Khonkaen, 40002, Thailand

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Nonthaburi, 11000, Thailand

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Aviv, 79013, Ukraine

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Dnipropetrovsk, 49074, Ukraine

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Dnipropetrovsk, 49102, Ukraine

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Donetsk, 83099, Ukraine

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Ivano-Frankivsk, 76025, Ukraine

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Kharkiv, 61018, Ukraine

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Kharkiv, 61035, Ukraine

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Kyiv, 02091, Ukraine

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Kyiv, 03680, Ukraine

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Luhansk, 91045, Ukraine

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Odesa, 65025, Ukraine

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Poltava, 36038, Ukraine

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Uzhhorod, 88015, Ukraine

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Related Publications (7)

• 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.

  PMID: 34922058 DERIVED

• 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.

  PMID: 30597021 DERIVED

• 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.

  PMID: 26702925 DERIVED

• 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.

  PMID: 25487791 DERIVED

• 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.

  PMID: 23357290 DERIVED

• 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.

  PMID: 21482570 DERIVED

• 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.

  PMID: 21482566 DERIVED

MeSH Terms

Conditions

Pneumonia, Bacterial; Community-Acquired Pneumonia; Haemophilus Infections

Interventions

Ceftaroline; Injections; Ceftriaxone; Clarithromycin

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Community-Acquired Infections; Pasteurellaceae Infections; Gram-Negative Bacterial Infections

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Administration Routes; Drug Therapy; Therapeutics; Cefotaxime; Cephacetrile; Erythromycin; Macrolides; Polyketides; Lactones

Results Point of Contact

• Title: Vice President, Clinical Sciences
• Organization: Cerexa, Inc

clinicaltrials@cerexa.com

(510) 285-9200

Study Officials

• Thomas M File, MD, MS

  Summa Health System

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2008
• First Posted: February 22, 2008
• Study Start: January 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: June 1, 2009
• Last Updated: March 14, 2017
• Results First Posted: November 10, 2010

Record last verified: 2017-02

Locations

SE (3); BR (12); ES (7); FR (5); HU (8); MY (5); SL (2); AU (2); BU (3); PL (17); CH (4); RU (13); DE (13); LI (6); UA (13); ZA (12); GE (2); RO (8); AR (10); TH (7); US (12); IN (1)