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

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

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.

Study Overview

• Status: Completed
• Conditions: Community-Acquired Bacterial Pneumonia; Lung Infection of Individual Not Recently Hospitalized
• Intervention / Treatment: Drug: Ceftaroline; Drug: Ceftriaxone

• Study Type: Interventional
• Enrollment (Actual): 848
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Research Site
  • Chengdu, China
    • Research Site
  • Guang Zhou, China
    • Research Site
  • Haikou, China
    • Research Site
  • Hangzhou, China
    • Research Site
  • Hefei, China
    • Research Site
  • Jiangyin, China
    • Research Site
  • Nanchang, China
    • Research Site
  • Shanghai, China
    • Research Site
  • Shenyang, China
    • Research Site
  • Shenzhen, China
    • Research Site
  • Shijiazhuang, China
    • Research Site
  • Wuxi, China
    • Research Site
• India
  • Bangalore, India
    • Research Site
  • Calicut, India
    • Research Site
  • Goa, India
    • Research Site
  • Hyderabad, India
    • Research Site
  • Jaipur, India
    • Research Site
  • Lucknow, India
    • Research Site
  • Ludhiana, India
    • Research Site
  • Mysore, India
    • Research Site
  • New Delhi, India
    • Research Site
  • Trivandrum, India
    • Research Site
  • Varanasi, India
    • Research Site
  • Vellore, India
    • Research Site
• Korea, Republic of
  • Anyang-si, Korea, Republic of
    • Research Site
  • Bucheon-si, Korea, Republic of
    • Research Site
  • Cheonan-si, Korea, Republic of
    • Research Site
  • Chuncheon-si, Korea, Republic of
    • Research Site
  • Daegu, Korea, Republic of
    • Research Site
  • Daejeon, Korea, Republic of
    • Research Site
  • Incheon, Korea, Republic of
    • Research Site
  • Seoul, Korea, Republic of
    • Research Site
  • Suwon-si, Korea, Republic of
    • Research Site
  • Wonju-si, Korea, Republic of
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan
    • Research Site
  • Keelung, Taiwan
    • Research Site
  • Taichung, Taiwan
    • Research Site
  • Taipei, Taiwan
    • Research Site
• Vietnam
  • Can Tho, Vietnam
    • Research Site
  • Hanoi, Vietnam
    • Research Site
  • Ho Chi Minh, Vietnam
    • Research Site
  • Hochiminh, Vietnam
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 150 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceftaroline	Drug: Ceftaroline; Two consecutive infusions q12h for 5 to 7 days
Active Comparator: Ceftriaxone plus placebo	Drug: Ceftriaxone; One dose infusion followed by IV saline placebo infused q24h for 5 to 7 days plus two consecutive saline placebo infusion q24h.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test of Cure (TOC) in CE Population	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 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	7-20 days after last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response at End of Treatment (EOT) Visit in MITT Population		Last day of study drug administration
Clinical Response at End of Treatment (EOT) Visit in CE Population		Last day of study drug administration
Clinical Response at the Test of Cure (TOC) Visit in MITT Population		7-20 days after last day of study drug administration
Clinical Response at the Test of Cure (TOC) Visit in mMITT Population		7-20 days after last day of study drug administration
Clinical Response at the Test of Cure (TOC) Visit in ME Population		7-20 days after last day of study drug administration
Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population		7-20 days after last dose of study drug
Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population		7-20 days after last dose of study drug
Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population	An outcome is considered as favourable if the per-pathogen response for that subject is either Eradication (An adequate source specimen demonstrates absence of the original baseline pathogen) or presumed eradication (An adequate source specimen was not available to culture and the patient was assessed as a clinical cure). Here, an adequate source specimen is defined as any sample that may yield the growth of a CABP pathogen eg, blood, respiratory specimens, or pleural fluid.	7-20 days after last day of study drug administration
Per-Patient Microbiological Response at Test of Cure (TOC) Visit in ME Population	An outcome is considered as favourable if the per-pathogen response for that subject is either Eradication (An adequate source specimen demonstrates absence of the original baseline pathogen) or presumed eradication (An adequate source specimen was not available to culture and the patient was assessed as a clinical cure). Here, an adequate source specimen is defined as any sample that may yield the growth of a CABP pathogen eg, blood, respiratory specimens, or pleural fluid.	7-20 days after last day of study drug administration
Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population		7-20 days after last day of study drug administration
Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in CE Population		7-20 days after last dose of study drug
Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population		21-42 days after last day of study drug administration
Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population		21-42 days after last day of study drug administration
Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population		21-42 days after last dose of study drug
Microbiological Re-infection/Recurrence at LFU Visit in ME Population		21-42 days after last dose of study drug

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Forest Laboratories

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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• D3720C00002 CSR Synopsis
• Revised CSP

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: April 27, 2011
• First Submitted That Met QC Criteria: June 10, 2011
• First Posted (Estimate): June 13, 2011

Study Record Updates

• Last Update Posted (Actual): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 1, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Community-Acquired Bacterial Pneumonia
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia; Pneumonia, Bacterial; Anti-Infective Agents; Anti-Bacterial Agents; Ceftriaxone; Ceftaroline fosamil
• Other Study ID Numbers: D3720C00002