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

Condition(s) targeted: Complicated Skin and Soft Tissue Infection

Intervention: Ceftaroline fosamil (Drug); Vancomycin (Drug); Aztreonam (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
David Melnick, MSD, Study Director, Affiliation: AstraZeneca

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.

Official title: 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.

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Clinical Cure as Measured by Comparing the Participants Signs and Symptoms at the Test of Cure (TOC) Visit to Those Recorded at Study Baseline in both the modified Intent-To-Treat and the Clinically Evaluable analysis sets

Secondary outcome:

The clinical cure rate in the modified intent-to-treat and clinically evaluable analysis sets

The per-patient microbiological favorable response in the microbiological modified intent-to-treat and microbiologically evaluable analysis sets

The clinical cure rate and per-pathogen microbiological favorable response by baseline pathogen in the microbiological modified intent-to-treat and microbiologically evaluable analysis sets

Clinical relapse in patients who were clinically cured at the test of cure visit in the clinically evaluable analysis set

Re-infection and recurrence rate in patients who were microbiological successes at the test of cure visits in the microbiologically evaluable analysis set

Super-infection rate in the microbiologically evaluable analysis set

New infection rate in the microbiologically evaluable analysis set

Colonization rate in patients who had a clinical assessment in the microbiologically evaluable analysis set

Early response rate in the modified intent-to-treat and clinically evaluable analysis sets

The safety and tolerability by incidence and severity of adverse events, vital signs, clinical laboratory tests, ECGs and physical exam

Description of population pharmacokinetics of ceftaroline and ceftaroline fosamil in this patient population.

PK profiles, including Cmax, Tmax, t½λz, AUC, plasma clearance, Vz, Vss, and mean residence time, of ceftaroline, ceftaroline fosamil and ceftaroline M-1 with intensive sampling in a subset of about 45 patients

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Research site, Cordoba, Argentina

Research site, Sao Jose do Rio Preto, Brazil

Research site, Pleven, Bulgaria

Research site, Temuco, Chile

Research site, Zagreb, Croatia

Research site, Athens, Greece

Research site, Haifa, Israel

Research site, Ramat-Gan, Israel

Research site, Safed, Israel

Research site, Tel-Aviv, Israel

Research site, Milano, Italy

Research site, Lodz, Poland

Research site, Bucharest, Romania

Research site, Dundee, South Africa

Research site, Worcester, South Africa

Research site, Granada, Spain

Research site, Terrassa, Spain

Research site, Ankara, Turkey

Research site, Diyarbakir, Turkey

Research site, Izmir, Turkey

Research site, Salvador, Bahia, Brazil

Research site, Passo Fundo, Rio Grande do Sul, Brazil

Starting date: June 2014
Last updated: January 28, 2015