Evaluation of Ceftaroline Fosamil Versus 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) 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

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 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 Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set | The observed difference in the clinical cure rates at TOC (ceftaroline group minus vancomycin plus aztreonam group) in MITT. Clinical cure rate is measured by comparing the participant's signs and symptoms at TOC visit to those recorded at study baseline. | 7 to 20 days after the last dose of study drug | 
| Clinical Response at TOC in Clinically Evaluable (CE) Analysis Set | The observed difference in the clinical cure rates at TOC (ceftaroline group minus vancomycin plus aztreonam group) in CE. Clinical cure rate is measured by comparing the participant's signs and symptoms at TOC visit to those recorded at study baseline. | 7 to 20 days after the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set | Difference in microbiological favorable response rate at TOC in mMITT analysis set. Favorable microbiological response rate is measured by comparing TOC microbiological data to baseline microbiological data. In the absence of TOC microbiological data it is presumed from the clinical response. | 7 to 20 days after the last dose of study drug | 
| Per-patient Micro Response at TOC in Microbiologically Evaluable (ME) Analysis Set | Difference in microbiological favorable response rate at TOC in ME. Favourable microbiological response rate is measured by comparing TOC microbiological data to baseline microbiological data. In the absence of TOC microbiological data it is presumed from the clinical response. | 7 to 20 days after the last dose of study drug | 
| Clinical Response at End of Treatment (EOT) in MITT Analysis Set | The observed difference in the clinical cure rates at EOT (ceftaroline group minus vancomycin plus aztreonam group) in MITT. Clinical cure rate is measured by comparing the participant's signs and symptoms at EOT visit to those recorded at study baseline. | On day of last dose of study drug (or + 1 day) | 
| Clinical Response at EOT in CE Analysis Set | The observed difference in the clinical cure rates at EOT (ceftaroline group minus vancomycin plus aztreonam group) in CE. Clinical cure rate is measured by comparing the participant's signs and symptoms at EOT visit to those recorded at study baseline. | On day of last dose of study drug (or +1 day) | 
| Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC | The observed difference in the clinical relapse rates at LFU (ceftaroline group minus vancomycin plus aztreonam group) in CE. Clinical relapse rate at LFU is measured by comparing a patient's signs and symptoms at late follow-up to those when they were cured at TOC. | 21 to 42 days after the last dose of study drug | 
| Early Response at 48 to 72 Hours of Treatment in MITT Analysis Set | The observed difference in the early success rates at 48 to 72 hours of treatment (ceftaroline group minus vancomycin plus aztreonam group) in MITT. Early response rate as measured by comparing the participant's signs and symptoms at the 48-72 hour visit to those recorded at study baseline. | 48 to 72 hours after first dose of study drug | 
| Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME | Per-pathogen microbiological response at TOC by baseline pathogen from site of skin infection in ME analysis set | 7 to 20 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 soft tissue infections (cSSTI), skin infection, ceftaroline, wound infection, cellulitis, burn infection, bacterial infection, vancomycin