Evaluation of Ceftaroline Fosamil Versus a Comparator in Adult Subjects With Community-acquired Bacterial Pneumonia (CABP) With Risk for Methicillin-resistant Staphylococcus Aureus

Study Overview
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Brief Summary
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The purpose of this study is to determine whether ceftaroline is effective and safe for the treatment of patients with Community-acquired Bacterial Pneumonia (CABP) at risk for infection due to Methicillin-resistant Staphylococcus aureus (MRSA).

Detailed Description
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A Multicenter, Multinational, Randomized, Double-blind Study to Evaluate the Efficacy and safety of Ceftaroline fosamil Versus Ceftriaxone Plus Vancomycin in Adult Subjects with Community-acquired Bacterial Pneumonia at Risk for Infection Due to Methicillin-resistant Staphylococcus aureus.

Official Title
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A Multicenter, Multinational, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Ceftaroline Fosamil Versus Ceftriaxone Plus Vancomycin in Adult Subjects With Community-acquired Bacterial Pneumonia at Risk for Infection Due to Methicillin-resistant Staphylococcus Aureus

Conditions
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Infections

Intervention / Treatment
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* Drug: Ceftaroline fosamil
* Drug: Ceftriaxone plus vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are required to meet All of the following inclusion criteria: Male or female, ≥ 18 years old Presence of CABP requiring hospitalization Presence of CABP meeting the following criteria: I. confirmed pneumonia (new or progressive pulmonary) II. Acute illness (≤ 7 days' duration) with at least 3 clinical signs or symptoms consistent with a lower respiratory tract infection MRSA Risk Factors • MRSA-positive blood culture or respiratory specimen or a risk factor for MRSA such as a history of colonization with MRSA Exclusion Criteria: Subjects must Not meet any of the following exclusion criteria at baseline: History of any hypersensitivity or allergic reaction to any β-lactam antimicrobial Suspected or microbiologically-documented infection with a pathogen known to be resistant to any of the study drugs Non-infectious causes of pulmonary infiltrates (eg, pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure) More than 24 hours of potentially effective systemic antibacterial therapy for CABP within 96 hours before randomization End-stage renal disease [Creatinine Clearance (CrCl) < 15], including hemodialysis Evidence of significant hepatic, hematological, or immunocompromising condition

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftaroline<br>Ceftaroline fosamil 600 mg Intravenous (IV) administration over 60 minutes, every 8 hours (q8h); dosing to be adjusted for renal function; treatment duration 5 to 14 days | Drug: Ceftaroline fosamil<br>* Ceftaroline fosamil 600 mg IV over 60 minutes q8h; treatment duration 5 to 14 days<br>* Other names: PPI0903 Teflaro;|
| Active Comparator: Ceftriaxone plus vancomycin<br>Ceftriaxone 2 g IV over 30 minutes once per day (q24h) plus vancomycin 15 mg/kg IV every 12 hours (q12h) initially and then dose adjusted based on trough concentrations; treatment duration 5 to 14 days | Drug: Ceftriaxone plus vancomycin<br>* Ceftriaxone 2g IV over 30 minutes q24h plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations; treatment duration 5 to 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response at Study Day 4 in the Modified Intent-to-Treat (MITT) Population | Clinical response was defined as meeting all of the following criteria: Symptom Improvement - Improvement in at least 2 and no worsening of any of the following symptoms compared to baseline: Cough Dyspnea Sputum production Chest pain Clinical Stability (per Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines; Mandell et al, 2007): Temperature ≤ 37.8°C Heart rate ≤ 100 beats/min Respiratory rate ≤ 24 breaths/min Systolic blood pressure ≥ 90 mmHg Oxygen saturation ≥ 90% Confusion/disorientation absent | Study Day 4 | 
| Clinical Outcome at Test of Cure (TOC) in the MITT Population | An assessment of clinical outcome was made by the Investigator at TOC. The clinical outcome categories were: Cure: Resolution of all acute signs and symptoms of CABP or improvement to such an extent that no further antimicrobial therapy was required Failure: Subjects who meet either of the following criteria: Incomplete resolution or worsening of CABP signs and symptoms or development of new CABP signs or symptoms requiring alternative nonstudy antimicrobial therapy Death in which CABP is contributory Indeterminate: Study data are not available for evaluation of efficacy for any reason, including: Death in which CABP is clearly noncontributory Lost to follow-up Extenuating circumstances precluding classification as a cure or failure A favorable clinical outcome at Test-of Cure (TOC) was clinical cure. | Test of Cure, an average of 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infections, Teflaro, cephalosporin, Ceftaroline, antibiotics, pneumonia