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

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01499277
First received: December 16, 2011
Last updated: November 18, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Complicated Skin and Soft Tissue Infection
Drug: Ceftaroline fosamil
Drug: Vancomycin
Drug: Aztreonam
Phase 3

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Clinical Response at Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set [ Time Frame: 7 to 20 days after the last dose of study drug ] [ Designated as safety issue: No ]
    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.

  • Clinical Response at TOC in Clinically Evaluable (CE) Analysis Set [ Time Frame: 7 to 20 days after the last dose of study drug ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set [ Time Frame: 7 to 20 days after the last dose of study drug ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7 to 20 days after the last dose of study drug ] [ Designated as safety issue: No ]
    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.

  • Clinical Response at End of Treatment (EOT) in MITT Analysis Set [ Time Frame: On day of last dose of study drug (or + 1 day) ] [ Designated as safety issue: No ]
    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.

  • Clinical Response at EOT in CE Analysis Set [ Time Frame: On day of last dose of study drug (or +1 day) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 21 to 42 days after the last dose of study drug ] [ Designated as safety issue: No ]
    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.

  • Early Response at 48 to 72 Hours of Treatment in MITT Analysis Set [ Time Frame: 48 to 72 hours after first dose of study drug ] [ Designated as safety issue: No ]
    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.

  • Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME [ Time Frame: 7 to 20 days after the last dose of study drug ] [ Designated as safety issue: No ]
    Per-pathogen microbiological response at TOC by baseline pathogen from site of skin infection in ME analysis set


Enrollment: 802
Study Start Date: May 2012
Study Completion Date: January 2015
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Ceftaroline fosamil
IV ceftaroline 600mg every 8 hours
Active Comparator: Vancomycin plus 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
Drug: Vancomycin
IV vancomycin 15mg/kg every 12 hours
Drug: Aztreonam
IV aztreonam 1 g every 8 hours

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
  Eligibility

Ages Eligible for Study:   18 Years to 99 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01499277

  Show 91 Study Locations
Sponsors and Collaborators
AstraZeneca
Forest Laboratories
Investigators
Study Director: David Melnick, MSD AstraZeneca
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01499277     History of Changes
Other Study ID Numbers: D3720C00001  2011-004013-16 
Study First Received: December 16, 2011
Results First Received: June 23, 2015
Last Updated: November 18, 2015
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Chile: Instituto de Salud Pública de Chile
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Croatia: Ministry of Health and Social Care
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hong Kong: Department of Health
Israel: Ministry of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Mexico: Federal Commission for Sanitary Risks Protection
Peru: Ministry of Health
Philippines: Bureau of Food and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Taiwan : Food and Drug Administration
Thailand: Food and Drug Administration
Turkey: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
complicated skin and soft tissue infections (cSSTI)
skin infection
ceftaroline
wound infection
cellulitis
burn infection
bacterial infection
vancomycin

Additional relevant MeSH terms:
Communicable Diseases
Infection
Soft Tissue Infections
Aztreonam
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 02, 2016