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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Community-Acquired Bacterial Pneumonia, Lung Infection of Individual Not Recently Hospitalized

Intervention / Treatment
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* Drug: Ceftaroline
* Drug: Ceftriaxone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 150 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Community-Acquired Bacterial Pneumonia