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

Phase 3

Completed

Conditions: Complicated Skin and Soft Tissue Infection

Interventions: Drug: Ceftaroline fosamil
Drug: Vancomycin
Drug: Aztreonam

Registration Number: NCT01499277

Lead Sponsor: Pfizer

Brief Summary: 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: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 802

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ceftaroline fosamil	Ceftaroline fosamil	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.
Vancomycin plus aztreonam	Vancomycin	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
Vancomycin plus aztreonam	Aztreonam	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

Primary Outcome Measures

Name	Time	Method
Clinical Response at TOC in Clinically Evaluable (CE) Analysis Set	7 to 20 days after the last dose of study drug	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.
Clinical Response at Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set	7 to 20 days after the last dose of study drug	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.

Secondary Outcome Measures

Name	Time	Method
Clinical Response at End of Treatment (EOT) in MITT Analysis Set	On day of last dose of study drug (or + 1 day)	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.
Early Response at 48 to 72 Hours of Treatment in MITT Analysis Set	48 to 72 hours after first dose of study drug	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.
Clinical Response at EOT in CE Analysis Set	On day of last dose of study drug (or +1 day)	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.
Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC	21 to 42 days after the last dose of study drug	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.
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME	7 to 20 days after the last dose of study drug	Per-pathogen microbiological response at TOC by baseline pathogen from site of skin infection in ME analysis set
Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set	7 to 20 days after the last dose of study drug	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.
Per-patient Micro Response at TOC in Microbiologically Evaluable (ME) Analysis Set	7 to 20 days after the last dose of study drug	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.