Adult Subjects with Community-Acquired Pneumonia MedDRA version: 9.1 Level: LLT Classification code 10010120 Term: Community acquired pneumonia
Conditions
Interventions
Product Name: Ceftaroline for Injection (Ceftaroline)
Product Code: USAN: Ceftaroline acetate
Pharmaceutical Form: Powder for solution for infusion
CAS Number: 866021-48-0
Current Sponsor code: Ceftar
Sponsors
Cerexa, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females 18 or more years of age 2. Community-acquired pneumonia meeting the following criteria: I. Radiographically-confirmed pneumonia (new or progressive pulmonary infiltrate(s) on chest radiograph (CXR) or chest computed tomography (CT) scan consistent with bacterial pneumonia) AND II. Acute illness (=7 days’ duration) with at least three of the following clinical signs or symptoms consistent with a lower respiratory tract infection: • New or increased cough • Purulent sputum or change in sputum character • Auscultatory findings consistent with pneumonia (e.g. rales, egophony, findings of consolidation) • Dyspnea, tachypnea, or hypoxemia (O2 saturation 38.5ºC rectally or tympanically) or hypothermia (=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. PORT score less than or equal to 70 (PORT Risk Class I or II), PORT score greater than 130 (PORT Risk Class V), or requiring admission to an intensive care unit 2. CAP suitable for outpatient therapy with an oral antimicrobial agent 3. Confirmed or suspected respiratory tract infections attributable to sources other than community-acquired bacterial pathogens 4. Non-infectious causes of pulmonary infiltrates 5. Pleural empyema 6. 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. Epidemiological clues to potential MRSA infection include residence in a nursing home or assisted living facility, existence of an ongoing MRSA infection outbreak, known skin colonisation with MRSA, resent skin or skin structure infection due to MRSA, intravenous drug use, and concomitant influenza. Subject with risk factors of MRSA infection who have predominance of Gram-positive cocci in clusters on sputum Gram's stain should also be excluded 7. infection with untypical organism is confirmed, or suspected based upon the epidemiological context, or infection with Legionella pneunmophilla is confirmed by the urinary antigene test at baseline 8. Previous treatment with an antimicrobial for treatment of CAP within 96 hours leading up to randomization EXCEPTIONS: subjects may be eligible despite prior antimicrobial therapy if they meet the following conditions: EITHER: • A single dose of an oral or intraqvenous shortacting antibiotic for CAP. OR BOTH OF THE FOLLOWING: • Unequivocal clinical evidence of treatment failure following at least 48 hours of prior systemic antimicrobial therapy • Isolation of an organism resistant to the prior, systemic, antimicrobial therapy 9. Failure of ceftriaxone (or other third-generation cephalosporin) as therapy for this episode of CAP, or prior isolation of an organism associated with this episode of CAP and resistant in vitro to ceftriaxone 10. History of any hypersensitivity or allergic reaction to any ß-lactam antimicrobial 11. Past or current history of epilepsy or seizure disorder 12. Requirement for concomitant antimicrobial or systemic antifungal therapy for any reason 13. Neoplastic lung disease, cystic fibrosis, progressively fatal disease, chronic neurological disorder preventing clearance of pulmonary secretions, or life expectancy of less than or equal to 3 months 14. Probenecid administration within 3 days prior to initiation of study drug therapy or requirement for concomitant therapy with probenecid 15. Infections or conditions requiring concomitant systemic corticosteroids 16. Severely impaired renal function (CrCl = 30 mL/min) estimated by the Cockroft-Gault formula 17. Evidence of significant hepatic, hematological, or immunologic disease determined by the following: - known acute viral hepatitis - AST, GOT or ALT level greater than 10-fold the upper limit of normal or total bilirubin greater than 3-fold the upper limit of normal - manifestations of ends-stage liver disease - current or anticipated neutropenia defined as less than 500 neutrophils/m3 - trombocitopenia with platelet count less than 60 000 cells /mm3 - known infection with HIDV and either CD4 count less than or equal to 200 cells/mm3 at the last measurement or current diagnosis of another AIDS-defining illness 18. Evidence of immediately life-threatening disease, 19. Residen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the non-inferiority in the overall (clinical and radiographic) success rate for ceftaroline compared to that for ceftriaxone at the Test-of-Cure (TOC) visit in the Clinically Evaluable (CE) and Modified Intent-to-Treat (MITT) populations in adult subjects with community-acquired pneumonia (CAP);Secondary Objective: • Evaluate the clinical response at the End-of-Therapy (EOT) and TOC visits • Evaluate the microbiological success rate at the TOC visit • Evaluate the clinical and microbiological response by pathogen at the TOC visit • Evaluate clinical relapse at the Late Follow-up (LFU) visit • Evaluate microbiological re-infection/recurrence at the LFU visit • Evaluate safety;Primary end point(s): The primary efficacy outcome measure will be the per-subject overall (combined clinical and radiographic) success rate at the TOC visit in the CE and MITT Populations. Overall response is defined as the combined clinical and radiographic responses. Subjects will be considered clinically cured at the TOC visit if they have total resolution of all signs and symptoms of the baseline infection, or improvement of the infection to such an extent that no further antimicrobial therapy is necessary. Radiographic success will be determined if the TOC visit CXR or chest CT scan is resolved, improved, or stable compared to the baseline CXR or CT scan. The overall response will be assessed programmatically by combining the clinical response with the radiographic response. To be an overall success the subject must be deemed a clinical cure and either a radiographic success or a radiographic indeterminate. The secondary efficacy outcome measures will be as follows: • Per-subject clinical cure rate at the TOC visit in the MITT, clinical MITT (cMITT), and CE populations • Per-subject clinical cure rate at the EOT visit in the MITT, cMITT, and CE populations • Per-subject microbiological success rate at the TOC visit in the microbiological MITT (mMITT) and Microbio | — |
Countries
Austria, Bulgaria, Germany, Hungary, Latvia
Outcome results
None listed