Evaluation of Ceftaroline Fosamil vs Vancomycin Plus Aztreonam in the Treatment of Patients With Skin Infections.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of Ceftaroline Fosamil versus Vancomycin plus Aztreonam in treatment of patients with complicated bacterial skin and soft tissue infections.

Detailed Description
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A Phase III, Multicentre, Randomised, Double-Blind Comparative Study to Evaluate the Efficacy and Safety of Ceftaroline Fosamil (600 mg every 8 hours) Versus Vancomycin Plus Aztreonam in the Treatment of Patients with Complicated Bacterial Skin and Soft Tissue Infections With Evidence of Systemic Inflammatory Response or Underlying Comorbidities

Official Title
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A Phase III, Multicentre, Randomised, Double-Blind Comparative Study to Evaluate the Efficacy and Safety of Ceftaroline Fosamil (600 mg Every 8 Hours) vs Vancomycin Plus Aztreonam in the Treatment of Patients With Complicated Bacterial Skin and Soft Tissue Infections With Evidence of Systemic Inflammatory Response or Underlying Comorbidities.

Conditions
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Complicated Skin and Soft Tissue Infection

Intervention / Treatment
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* Drug: Ceftaroline fosamil
* Drug: Vancomycin
* Drug: Aztreonam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 years or older - Complicated skin and skin structure infection (cSSTI) - Infection of sufficient severity to warrant hospitalization - Infection of sufficient severity such that it is expected to require at least 5 days of intravenous antibiotic therapy. patients must have a positive culture for MRSA that has been obtained from the skin infection site and/or blood samples at any time within the 72hrs before the first dose. Exclusion Criteria: Received systemic antibacterial drugs for greater than 24 hours within 96 hours prior to first dose of study drug - Uncomplicated skin and skin structure infections, skin infections suspected to be caused by viral or fungal pathogens - Diabetic foot infections, decubitus ulcers, ulcers due to peripheral vascular disease - Infection caused by human or animal bites, sternal wound infections, bone infection or arthritis due to an infection, critical limb ischemia of the affected limb - Chronic liver disease or severe impaired renal function, severe low white blood cell count, burns on greater than 15% of total body surface area, necrotizing skin infection, amputation required of primary site of infection, sustained shock

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftaroline fosamil<br>Patients will receive 600 mg of ceftaroline fosamil administered as a 120-minute intravenous infusion very 8 hours. Each dose will be infused in a volume of 250 mL over 120-minutes followed by aztreonam placebo in a volume of 100 mL infused over 30 minutes every 8 hours. In addition vancomycin placebo will be given in a volume of 250 mL infused over 120 minutes every 12 hours. Doses will be adjusted according to the patient's renal function. | Drug: Ceftaroline fosamil<br>* IV ceftaroline 600mg every 8 hours<br>|
| Active Comparator: Vancomycin plus aztreonam<br>Patients will receive combination of vancomycin plus aztreonam. Dose of vancomycin will be based on the patient's actual weight and will receive intravenous vancomycin every 12 hours with each dose infused over 120-minutes. Aztreonam dose will be 1 gram intravenously in a volume of 100 mL infused over 30 minutes every 8 hours. In addition, ceftaroline fosamil placebo will be given in a volume of 250 mL infused over 120 minutes every 8 hours. Doses adjusted according to patients renal function | Drug: Vancomycin<br>* IV vancomycin 15mg/kg every 12 hours<br>Drug: Aztreonam<br>* IV aztreonam 1 g every 8 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response at TOC | Clinical cure is defined as resolution or improvement of signs and symptoms compared to baseline and no further antimicrobial therapy is necessary. Clinical failure is defined as any of the following: persistence or worsening in signs or symptoms, or requirement for concomitant antibiotic therapy, or requirement of an unplanned surgical intervention >48 hours after the first dose, or death caused by skin infection, or an AE leading to study drug discontinuation with alternative antimicrobial therapy required, or diagnosis of osteomyelitis >=8 days after the first dose. | 7 to 20 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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complicated skin and soft tissue infections (cSSTI), skin infection, ceftaroline, wound infection, cellulitis, burn infection, bacterial infection, vancomycin