Efficacy and Safety of Ceftaroline Versus Linezolid in Subjects With Complicated Skin and Skin Structure Infections

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 in the treatment of complicated skin and skin structure infections in adults.

Detailed Description
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The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of complicated skin and skin structure infections in adults. The primary focus is bacterial infection.

Official Title
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A Phase 2, Multicenter, Randomized, Open-label, Comparative Study to Evaluate the Efficacy and Safety of Intramuscular Ceftaroline Versus Intravenous Linezolid in Adult Subjects With Complicated Skin and Skin Structure Infections

Conditions
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Bacterial Infection

Intervention / Treatment
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* Drug: ceftaroline
* Drug: linezolid
* Drug: Aztreonam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Complicated skin and skin structure infection (cSSSI) Require initial hospitalization, or treatment in an emergency room or urgent care setting Exclusion Criteria: Hypersensitivity or allergic reaction to any ß-lactam, ceftaroline, linezolid, aztreonam, or to their components Concomitant use of adrenergic or serotonergic agent Uncomplicated skin and skin structure infection Concomitant therapy with any drug known to exhibit a contraindicated drug-drug interaction More than 24 hours of treatment with an antimicrobial within 96 hours before randomization Known or suspected endocarditis, osteomyelitis, or septic arthritis Severely impaired renal function Evidence of significant hepatic, hematologic, or immunologic disease

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftaroline<br>Intramuscular every 12 hours | Drug: ceftaroline<br>* 600 mg injected every 12 hours for at least 5 but not more than 14 days<br>* Other names: ceftaroline for injection;|
| Active Comparator: linezolid plus optional aztreonam<br>Intravenous every 12 hours | Drug: linezolid<br>* 600 mg parenteral infused over 60 minutes for a minimum of 5 days and a maximum of 14 days<br>* Other names: CAS number 165800-03-3;Drug: Aztreonam<br>* 1000 mg infused over 60 minutes every 24 hours may be started with linezolid or added later (up to 72 hours after the first dose of linezolid) for subjects with a gram-negative infection indicated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response at the Test of Cure (TOC) Visit in the Modified Intent-to-treat (MITT) Population | The coprimary efficacy outcome measures were the per-subject clinical cure rate at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) and (Modified-Intent-to-Treat) MITT Populations. Subjects were considered clinically cured at the Test of Cure (TOC) Visit if they had 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 was necessary. | Test of Cure Visit (8 to 15 days after end of therapy) | 
| Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population | The coprimary efficacy outcome measures were the per-subject clinical cure rate at the TOC Visit in the CE and MITT Populations. Subjects were considered clinically cured at the TOC Visit if they had 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 was necessary. | Test of Cure Visit (8 to 15 Days after end of therapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure Rate at the TOC Visit in the cMITT Population | Evaluate per-subject the clinical response at the Test-of-Cure (TOC) Visit in the Clinical Modified Intent-to-treat (cMITT) Population. | TOC Visit (8 to 15 days after end of therapy) | 
| Clinical Response at the End-of-Therapy (EOT) Visit in the MITT, cMITT and CE Populations. | Evaluate per-subject the clinical response at the End-of-therapy (EOT) Visit in the MITT, cMITT and CE populations. | End-of-therapy (EOT) visit | 
| The Microbiological Response at the TOC Visit in the mMITT and ME Populations. | Evaluate per-subject the microbiological response at the TOC Visit in the Microbiological Modified Intent-to-treat (mMITT) and Microbiologically Evaluable (ME) populations. | TOC Visit (8 to 15 days after end of therapy) | 
| Clinical and Microbiological Response by Pathogen at the TOC Visit in the mMITT and ME Populations | Evaluate the clinical and microbiological response by pathogen at the TOC Visit in the mMITT and ME populations. | TOC Visit (8 to 15 days after end of therapy) | 
| Clinical Relapse at the Late Follow-up Visit | Evaluate Clinical relapse rate at Late Follow-up (LFU) (21 to 45 days after the final dose of study drug)in those subjects clinically cured at the TOC visit. | Late Follow-up (LFU) Visit (21 to 35 days after end of therapy) | 
| The Microbiological Reinfection or Recurrence at the Late Follow-up (LFU) Visit | Evaluate per-subject reinfection or recurrence rate at the LFU Visit in those subjects who had a favorable microbiological outcome (eradication or presumed eradication) at the TOC Visit. | LFU Visit (21 to 35 days after end of therapy) | 
| The Safety of Ceftaroline Fosamil | Evaluate safety of Ceftaroline fosamil IM in adults with complicated skin and skin structure infection (cSSSI) | First dose of study drug through LFU Visit or 30 days after the last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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complicated skin and skin structure infections, linezolid, ceftaroline, clinical response, microbiological response, Cellulitis, Abscess, Wound infection, Deeper soft tissue, Significant surgical intervention, Gram-positive bacterial infection, Gram-negative bacterial infection, bacterial infection, cephalosporin, broad-spectrum activity