Evaluation of Ceftaroline Fosamil Versus 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: Completed

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) 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

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 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, Córdoba, Argentina

Research Site, Santa Fe, Argentina

Research Site, Parkville, Australia

Research Site, Bruxelles, Belgium

Research Site, Belo Horizonte, Brazil

Research Site, Passo Fundo, Brazil

Research Site, Salvador, Brazil

Research Site, São José do Rio Preto, Brazil

Research Site, Pleven, Bulgaria

Research Site, Ruse, Bulgaria

Research Site, Sofia, Bulgaria

Research Site, Temuco, Chile

Research Site, Viña del Mar, Chile

Research Site, Beijing, China

Research Site, Changchun, China

Research Site, Changsha, China

Research Site, Chengdu, China

Research Site, Chongqing, China

Research Site, Fuzhou, China

Research Site, Guangzhou, China

Research Site, Haikou, China

Research Site, Nanning, China

Research Site, Qingdao, China

Research Site, Shanghai, China

Research Site, Shenyang, China

Research Site, Shijiazhuang, China

Research Site, Wuhan, China

Research Site, Xi'an, China

Research Site, Slavonski Brod, Croatia

Research Site, Zagreb, Croatia

Research Site, Jihlava, Czech Republic

Research Site, Pardubice, Czech Republic

Research Site, Orleans, France

Research Site, Dessau, Germany

Research Site, Hanau, Germany

Research Site, Heilbronn, Germany

Research Site, Athens, Greece

Research Site, Kowloon, Hong Kong

Research Site, Pokfulam, Hong Kong

Research Site, Haifa, Israel

Research Site, Ramat-Gan, Israel

Research Site, Safed, Israel

Research Site, Tel Aviv, Israel

Research Site, Milano, Italy

Research Site, Ansan, Korea, Republic of

Research Site, Deagu, Korea, Republic of

Research Site, Incheon, Korea, Republic of

Research Site, Seoul, Korea, Republic of

Research Site, Won-ju, Korea, Republic of

Research Site, Guadalajara, Mexico

Research Site, Cusco, Peru

Research Site, Lima, Peru

Research Site, Manila, Philippines

Research Site, Quezon City, Philippines

Research Site, Lublin, Poland

Research Site, Łódź, Poland

Research Site, Bucharest, Romania

Research Site, Moscow, Russian Federation

Research Site, Perm, Russian Federation

Research Site, Saint Petersburg, Russian Federation

Research Site, Smolensk, Russian Federation

Research Site, Vsevolozhsk, Russian Federation

Research Site, Yaroslavl, Russian Federation

Research Site, Benoni, South Africa

Research Site, Cape Town, South Africa

Research Site, Johannesburg, South Africa

Research Site, Worcester, South Africa

Research Site, Barcelona, Spain

Research Site, Granada, Spain

Research Site, Madrid, Spain

Research Site, Terrassa, Spain

Research Site, Kaohsiung, Taiwan

Research Site, Taipei, Taiwan

Research Site, Yung Kang City, Taiwan

Research Site, Ankara, Turkey

Research Site, Diyarbakir, Turkey

Research Site, Izmir, Turkey

Research Site, Cherkasy, Ukraine

Research Site, Ivano-Frankivsk, Ukraine

Research Site, Kharkov, Ukraine

Research Site, Odesa, Ukraine

Research Site, Chula Vista, California, United States

Research Site, Orlando, Florida, United States

Research Site, West Palm Beach, Florida, United States

Research Site, Carmel, Indiana, United States

Research Site, Hazard, Kentucky, United States

Research Site, Springfield, Massachusetts, United States

Research Site, Detroit, Michigan, United States

Research Site, Las Vegas, Nevada, United States

Research Site, Garden City, New York, United States

Research Site, Bellaire, Texas, United States

Starting date: May 2012
Last updated: July 25, 2014