Comparative Study of Ceftaroline vs. Ceftriaxone in Adult Subjects With Community-Acquired Pneumonia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of Community-Acquired Pneumonia

Detailed Description
-----------------
The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of Community-Acquired Pneumonia. Clinical trials for this study is held in many countries

Official Title
-----------------
A Phase 3, Multicenter, Randomized, Double-blind, Comparative Study to Evaluate the Safety and Efficacy of Ceftaroline Versus Ceftriaxone, With Adjunctive Clarithromycin, in the Treatment of Adult Subjects With Community-Acquired Pneumonia

Conditions
-----------------
Bacterial Pneumonia

Intervention / Treatment
-----------------
* Drug: Ceftaroline fosamil for Injection
* Drug: IV Ceftriaxone
* Drug: Placebo
* Drug: Clarithromycin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects are required to meet the following inclusion criteria: Community-acquired pneumonia initial hospitalization, or treatment in an emergency room or urgent care setting infection would require initial treatment with IV antimicrobials. Exclusion Criteria: Subjects must NOT meet any of the following exclusion criteria: CAP suitable for outpatient therapy with an oral antimicrobial agent respiratory tract infections not due to community-acquired bacterial Non-infectious causes of pulmonary infiltrates Pleural empyema Infection with an atypical organism History of any hypersensitivity or allergic reaction to any ß-lactam antimicrobial History of any hypersensitivity or allergic reaction to clarithromycin or any macrolide/ ketolide

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftaroline fosamil for Injection<br>Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h). In both treatment groups, two doses of oral clarithromycin (500 mg q12h), defined as adjunctive therapy, were initiated on Study Day 1 with study drug therapy in order to provide an immunomodulatory benefit and initial therapy for possible infection due to an atypical organism. | Drug: Ceftaroline fosamil for Injection<br>* 2 consecutive, 300 mg dose parenteral infused over 30 minutes, every 12 hours, for 5 to 7 days<br>Drug: Clarithromycin<br>* In both treatment groups, two doses of oral clarithromycin (500 mg q12h), defined as adjunctive therapy, were initiated on Study Day 1 with study drug therapy in order to provide an immunomodulatory benefit and initial therapy for possible infection due to an atypical organism.<br>|
| Active Comparator: IV Ceftriaxone<br>Ceftriaxone was administered as a 1-g IV infusion over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h). In both treatment groups, two doses of oral clarithromycin (500 mg q12h), defined as adjunctive therapy, were initiated on Study Day 1 with study drug therapy in order to provide an immunomodulatory benefit and initial therapy for possible infection due to an atypical organism. | Drug: IV Ceftriaxone<br>* 1 g dose parenteral infused over 30 minutes, every 24 hours, for 5 to 7 days<br>* Other names: Ceftriaxone;Drug: Placebo<br>* Subjects randomized to receive ceftriaxone will receive ceftriaxone at a dose of 1 g infused over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h). Twelve hours after each dose of ceftriaxone and saline placebo (ie, between ceftriaxone doses), subjects in this group will receive two consecutive saline placebo infusions, each infused over 30 minutes q24h. The ceftriaxone and saline placebo infusions will correspond to the q12h infusions of ceftaroline, thereby maintaining the blind<br>Drug: Clarithromycin<br>* In both treatment groups, two doses of oral clarithromycin (500 mg q12h), defined as adjunctive therapy, were initiated on Study Day 1 with study drug therapy in order to provide an immunomodulatory benefit and initial therapy for possible infection due to an atypical organism.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations | 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 adverse event (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 | 8 to 15 days after last dose of study drug | 
| Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test-of-Cure (TOC) in the Clinically Evaluable (CE) Population |  | 8-15 days after last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response at End of Therapy (EOT) |  | Last day of study drug administration | 
| Microbiological Success Rate at Test of Cure (TOC) |  | 8-15 days after last dose of study drug | 
| Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) |  | 8-15 days after last day of study drug | 
| Clinical and Microbiological Response by Pathogen at TOC |  | 8-15 days after last dose of study drug | 
| Clinical Relapse at Late Follow Up (LFU) |  | 21-35 days after last dose of study drug | 
| Microbiological Re-infection/Recurrence at LFU |  | 21 to 35 days after last dose of study drug | 
| Evaluate Safety |  | first dose, throughout the treatment period, and up to the TOC visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ceftaroline, Community-acquired pneumonia, CAP, IV (intravenous), Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila spp, Legionella spp, Multi-drug resistant Streptococcus pneumoniae (MDRSP), antimicrobial resistance, pneumococci, Ceftriaxone, bacteria, ß-lactam, beta-lactam, antibiotic