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

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ClinicalTrials.gov Identifier: NCT01499277
Recruitment Status : Completed
First Posted : December 26, 2011
Results First Posted : November 9, 2015
Last Update Posted : September 6, 2017
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE December 16, 2011
First Posted Date  ICMJE December 26, 2011
Results First Submitted Date  ICMJE June 23, 2015
Results First Posted Date  ICMJE November 9, 2015
Last Update Posted Date September 6, 2017
Study Start Date  ICMJE May 2012
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2015)
  • 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 ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 22, 2011)
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 [ Time Frame: 8 to 15 days after the last dose of study drug ]
Change History Complete list of historical versions of study NCT01499277 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2015)
  • 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 ]
    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 ]
    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) ]
    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) ]
    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 ]
    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 ]
    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 ]
    Per-pathogen microbiological response at TOC by baseline pathogen from site of skin infection in ME analysis set
Original Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2011)
  • The clinical cure rate in the modified intent-to-treat and clinically evaluable analysis sets [ Time Frame: within 24 hours of completion of last infusion of study drug ]
  • The per-patient microbiological favorable response in the microbiological modified intent-to-treat and microbiologically evaluable analysis sets [ Time Frame: within 24 hours of completion of the last infusion of study drug and 8 to 15 days after the last dose of study drug ]
  • 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 [ Time Frame: 8 to 15 days after the last dose of study drug ]
  • Clinical relapse in patients who were clinically cured at the test of cure visit in the clinically evaluable analysis set [ Time Frame: 21 to 35 days after the last dose of study drug ]
  • Re-infection and recurrence rate in patients who were microbiological successes at the test of cure visits in the microbiologically evaluable analysis set [ Time Frame: 21 to 35 days after the last dose of study drug ]
  • Super-infection rate in the microbiologically evaluable analysis set [ Time Frame: within 24 hours of completion of the last infusion of study drug ]
  • New infection rate in the microbiologically evaluable analysis set [ Time Frame: 8 to 15 days after the last dose of study drug ]
  • Colonization rate in patients who had a clinical assessment in the microbiologically evaluable analysis set [ Time Frame: within 24 hours of completion of the last infusion of study drug or 8 to 15 days after the last dose of study drug ]
  • Early response rate in the modified intent-to-treat and clinically evaluable analysis sets [ Time Frame: at 48 to 72 hours of treatment ]
  • The safety and tolerability by incidence and severity of adverse events, vital signs, clinical laboratory tests, ECGs and physical exam [ Time Frame: study duration (26 days up to 51 days) ]
  • Description of population pharmacokinetics of ceftaroline and ceftaroline fosamil in this patient population. [ Time Frame: Within 15 minutes prior to start of infusion, 120 min +/- 5 min following start of infusion through end of infusion, 3-5 hours after start of infusion, and 6-8 hours after start of study drug and prior to next infusion ]
  • 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 [ Time Frame: Within 15 minutes prior to start of infusion and following the start of infusion at 60, 90, 115, 125, 135 minutes and 2.5, 3, 4, 5, 6, and 8 hours ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam in the Treatment of Patients With Skin Infections
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Complicated Skin and Soft Tissue Infection
Intervention  ICMJE
  • Drug: Ceftaroline fosamil
    IV ceftaroline 600mg every 8 hours
  • Drug: Vancomycin
    IV vancomycin 15mg/kg every 12 hours
  • Drug: Aztreonam
    IV aztreonam 1 g every 8 hours
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Ceftaroline fosamil
  • 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
    Interventions:
    • Drug: Vancomycin
    • Drug: Aztreonam
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 7, 2015)
802
Original Estimated Enrollment  ICMJE
 (submitted: December 22, 2011)
765
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Chile,   China,   Croatia,   Czechia,   France,   Germany,   Greece,   Hong Kong,   Israel,   Italy,   Korea, Republic of,   Mexico,   Peru,   Philippines,   Poland,   Romania,   Russian Federation,   South Africa,   Spain,   Taiwan,   Turkey,   Ukraine,   United States
Removed Location Countries Austria,   Colombia,   Czech Republic,   Hungary,   India,   Slovakia,   Thailand,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01499277
Other Study ID Numbers  ICMJE D3720C00001
2011-004013-16
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Forest Laboratories
Investigators  ICMJE
Study Director: David Melnick, MSD AstraZeneca
PRS Account Pfizer
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP