Clinical trial NCT01371838: A Study to Evaluate the Efficacy and Safety of Intravenous Ceftaroline Versus Intravenous Ceftriaxone in the Treatment of Adult Hospitalised Patients With Community-Acquired Bacterial Pneumonia in Asia
Official title: A Phase III, Multicentre, Randomised, Double-Blind, Comparative Study to Evaluate the Efficacy and Safety of Intravenous Ceftaroline Versus Intravenous Ceftriaxone in the Treatment of Adult Hospitalised Patients With Community-Acquired Bacterial Pneumonia in Asia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Community-Acquired Bacterial Pneumonia
Lung Infection of Individual Not Recently Hospitalized
Keywords: Community-Acquired Bacterial Pneumonia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Forest Laboratories
First posted: 2011-06-13
Enrollment: 848
Sex: ALL
Minimum age (years): 18
Maximum age (years): 150
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This purpose of this study is to Evaluate the Efficacy and Safety of Intravenous Ceftaroline Versus Intravenous Ceftriaxone in the Treatment of Adult Hospitalised Patients With Community-Acquired Bacterial Pneumonia in Asia.


Eligibility criteria: Inclusion Criteria:

* Males and females 18 or more years of age
* Lung Infection of Individual not Recently Hospitalized meeting the following criteria: Radiographically-confirmed pneumonia (new or progressive infection site of the lungs) consistent with bacterial pneumonia), AND Acute illness (≤ 7 days duration) with at least three of the following clinical signs or symptoms consistent with lung infection: New or increased cough, Purulent sputum or change in sputum character, Auscultatory findings consistent with pneumonia, Difficulty in breathing, short breath, or decreased partial pressure of oxygen in blood, Fever greater than 38ºC oral or body temperature lower than that required for normal body function(\< 35ºC), White blood cell count greater than or less than the normal, Greater than 15% immature neutrophils (bands) irrespective of white blood cell count, AND Moderate lung infection
* The subject must require initial hospitalization, or treatment in an emergency room or urgent care setting, by the standard of care
* The subject's infection would require initial treatment with intravenous antimicrobials
* Female subjects of child-bearing potential, and those who are fewer than 2 years post-menopausal, must agree to, and comply with, using highly effective methods of birth control while participating in this study

Exclusion Criteria:

* Lung Infection of Individual not Recently Hospitalized suitable for outpatient therapy with an oral antimicrobial agent
* Confirmed or suspected respiratory tract infections attributable to sources other than bacteria from the individuals not recently hospitalized(e.g., ventilator-associated pneumonia, hospital-acquired pneumonia, visible/gross aspiration pneumonia, suspected viral, fungal, or mycobacterial infection of the lung)
* Non-infectious causes of lung lesion (e.g., pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure)
* Accumulation of pus in the pleural cavity
* Microbiologically-documented infection with a pathogen known to be resistant to ceftriaxone, or epidemiological or clinical context suggesting high likelihood of a ceftriaxone-resistant "typical" bacterial pathogen.

Primary outcomes:
measure: Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test of Cure (TOC) in CE Population
timeFrame: 7-20 days after last dose of study drug
Secondary outcomes:
measure: Clinical Response at End of Treatment (EOT) Visit in MITT Population
timeFrame: Last day of study drug administration
measure: Clinical Response at End of Treatment (EOT) Visit in CE Population
timeFrame: Last day of study drug administration
measure: Clinical Response at the Test of Cure (TOC) Visit in MITT Population
timeFrame: 7-20 days after last day of study drug administration
measure: Clinical Response at the Test of Cure (TOC) Visit in mMITT Population
timeFrame: 7-20 days after last day of study drug administration
measure: Clinical Response at the Test of Cure (TOC) Visit in ME Population
timeFrame: 7-20 days after last day of study drug administration
measure: Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population
timeFrame: 7-20 days after last dose of study drug
measure: Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population
timeFrame: 7-20 days after last dose of study drug
measure: Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population
timeFrame: 7-20 days after last day of study drug administration
measure: Per-Patient Microbiological Response at Test of Cure (TOC) Visit in ME Population
timeFrame: 7-20 days after last day of study drug administration
measure: Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population
timeFrame: 7-20 days after last day of study drug administration
measure: Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in CE Population
timeFrame: 7-20 days after last dose of study drug
measure: Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population
timeFrame: 21-42 days after last day of study drug administration
measure: Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population
timeFrame: 21-42 days after last day of study drug administration
measure: Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population
timeFrame: 21-42 days after last dose of study drug
measure: Microbiological Re-infection/Recurrence at LFU Visit in ME Population
timeFrame: 21-42 days after last dose of study drug
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Guang Zhou
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Jiangyin
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Calicut
country: India
facility: Research Site
city: Goa
country: India
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
city: Jaipur
country: India
facility: Research Site
city: Lucknow
country: India
facility: Research Site
city: Ludhiana
country: India
facility: Research Site
city: Mysore
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Trivandrum
country: India
facility: Research Site
city: Varanasi
country: India
facility: Research Site
city: Vellore
country: India
facility: Research Site
city: Anyang-si
country: Korea, Republic of
facility: Research Site
city: Bucheon-si
country: Korea, Republic of
facility: Research Site
city: Cheonan-si
country: Korea, Republic of
facility: Research Site
city: Chuncheon-si
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Daejeon
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Wonju-si
country: Korea, Republic of
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Keelung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Can Tho
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Hochiminh
country: Vietnam
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: David Melnick
role: STUDY_DIRECTOR
References:
citation: Zhuo C, Huang Y, Liu W, Xu JF, Zhu WY, Stone GG, Yan JL, Mohamed N. Efficacy and Safety of Ceftaroline Fosamil in Hospitalized Patients with Community-Acquired Pneumonia in China: Subset Analysis of an International Phase 3 Randomized Controlled Trial. Infect Drug Resist. 2022 Feb 23;15:605-617. doi: 10.2147/IDR.S342558. eCollection 2022.
citation: 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.
citation: Li J, Das S, Zhou D, Al-Huniti N. Population Pharmacokinetic Modeling and Probability of Target Attainment Analyses in Asian Patients With Community-Acquired Pneumonia Treated With Ceftaroline Fosamil. Clin Pharmacol Drug Dev. 2019 Jul;8(5):682-694. doi: 10.1002/cpdd.673. Epub 2019 May 1.
citation: 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.
citation: Das S, Li J, Iaconis J, Zhou D, Stone GG, Yan JL, Melnick D. Ceftaroline fosamil doses and breakpoints for Staphylococcus aureus in complicated skin and soft tissue infections. J Antimicrob Chemother. 2019 Feb 1;74(2):425-431. doi: 10.1093/jac/dky439.
citation: 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.
citation: Zhong NS, Sun T, Zhuo C, D'Souza G, Lee SH, Lan NH, Chiang CH, Wilson D, Sun F, Iaconis J, Melnick D. Ceftaroline fosamil versus ceftriaxone for the treatment of Asian patients with community-acquired pneumonia: a randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial. Lancet Infect Dis. 2015 Feb;15(2):161-71. doi: 10.1016/S1473-3099(14)71018-7. Epub 2014 Dec 22.