Comparative Study of Ceftaroline vs. Vancomycin Plus Aztreonam in Adult Subjects With Complicated Skin Infections

A Phase 3, Multicenter, Randomized, Double-blind, Comparative Study to Evaluate the Safety and Efficacy of Ceftaroline Versus Vancomycin Plus Aztreonam in Adult Subjects With Complicated Skin and Skin Structure Infection (cSSSI)

The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of complicated skin infections in adults.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: ceftaroline; Drug: Placebo; Drug: vancomycin plus aztreonam

Detailed Description

Additional purpose of this study is to compare ceftaroline effectivity versus Vancomycin plus Aztreonam in the treatment of complicated skin infections in adults.

• Study Type: Interventional
• Enrollment (Actual): 680
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Investigational site
  • Cordoba, Argentina
    • Investigational site
  • Santa Fe, Argentina
    • Investigational site
• Austria
  • Braunau, Austria
    • Investigational site
  • Graz, Austria, 8036
    • Investigational site
  • St. Polten, Austria, 3100
    • Investigational site
• Brazil
  • Sao Paula, Brazil
    • Investigational site
• Chile
  • Temuco, Chile
    • Investigational site
  • Valdivia, Chile
    • Investigational site
• Germany
  • Cottbus, Germany, 03048
    • Investigational site
  • Dortmund, Germany, 44145
    • Investigational site
  • Homburg/Saar, Germany, D-66421
    • Investigational site
  • Mainz, Germany, D-55101
    • Investigational site
  • Wiesbaden, Germany, 65191
    • Investigational site
• Latvia
  • Riga, Latvia, LV-1001
    • Investigational site
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Investigational site
    • Seattle Zapopan, Jalisco, Mexico, 45170
      • Investigational site
• Poland
  • Bielsko-Biala, Poland, 43-316
    • Investigational site
  • Krakow, Poland, 31-501
    • Investigational site
  • Kraków, Poland, 31-820
    • Investigational site
  • Lodz, Poland, 91-425
    • Investigational site
  • Lublin, Poland, 20-954
    • Investigational site
  • Poznań, Poland, 61-848
    • Investigational site
  • Warszawa, Poland, 02-097
    • Investigational site
  • Warszawa, Poland, 03-401
    • Investigational site
  • Wroclaw, Poland, 50-326
    • Investigational site
• Russian Federation
  • Moscow, Russian Federation, 111020
    • Investigational site
  • Moscow, Russian Federation, 119048
    • Investigational site
  • Moscow Region, Russian Federation, 143405
    • Investigational site
  • St. Petersburg, Russian Federation, 192242
    • Investigational site
  • St. Petersburg, Russian Federation
    • Investigational site
• Ukraine
  • Kharkov, Ukraine, 61176
    • Investigational site
  • Kyiv, Ukraine, 03110
    • Investigational site
  • Lviv, Ukraine, 79044
    • Investigational site
  • Zaporizhya, Ukraine, 69000
    • Investigational site
• United Kingdom
  • London, United Kingdom, N19 5LW
    • Investigational site
  • London, United Kingdom, SW10 9NH
    • Investigational site
• United States
  • California
    • Buena Park, California, United States, 90620
      • Investigational site
    • Hawaiian Gardens, California, United States, 90716
      • Investigational site
    • Los Angeles, California, United States, 90033
      • Investigational site
    • Pasadena, California, United States, 91105
      • Investigational site
    • San Diego, California, United States, 92114
      • Investigational site
    • San Jose, California, United States, 95124
      • Investigational site
  • Florida
    • Atlantis, Florida, United States, 33462
      • Investigational site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Investigational site
    • Marietta, Georgia, United States, 30060
      • Investigational site
  • Illinois
    • Springfield, Illinois, United States, 62701
      • Investigational site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Investigational site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422
      • Investigational site
  • Montana
    • Butte, Montana, United States, 59701
      • Investigational site
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
      • Investigational site
  • Ohio
    • Toledo, Ohio, United States, 43608
      • Investigational site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Investigational site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Investigational site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Skin and skin structure infection (SSSI) that involves deeper soft tissue or requires significant surgical intervention, or cellulitis or abscess on lower extremity which occurs in subjects with diabetes mellitus or well-documented peripheral vascular disease.

Exclusion Criteria:

• Prior treatment of current complicated skin and skin structure infection (cSSSI) with an antimicrobial.
• Failure of vancomycin or aztreonam as therapy for the current cSSSI, or prior isolation of an organism with in vitro resistance to vancomycin or aztreonam.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceftaroline fosamil for Injection; Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours.	Drug: ceftaroline; 600 mg parenteral infused over 60 minutes, every 12 hours for 5 to 14 days; Other Names: Experimental; Drug: Placebo; Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours.
Active Comparator: IV Vancomycin plus IV Aztreonam; Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours.	Drug: vancomycin plus aztreonam; vancomycin at 1 g parenteral infused over 60 minutes followed by aztreonam 1 g infused over 60 minutes, every 12 hours, for 5 to 14 days.; Other Names: Active Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure Rate at Test of Cure (TOC) (MITT Population)	Cure: Total resolution of all signs and symptoms of the baseline infection, or improvement of the infection such that no further antimicrobial therapy was necessary. Failure: Requirement of alternative antimicrobial therapy for primary infection of complicated skin and skin structure infection (cSSSI) due to inadequate response, recurrence, new infection at the same site; treatment-limiting adverse event (AE); requirement for surgery due to failure of study drug; diagnosis of osteomyelitis after Study Day 8; or death caused by cSSSI. Indeterminate: Inability to determine an outcome	8-15 days after last dose of study drug administration
The Primary Efficacy Outcome Measure Was the Per-subject Clinical Cure Rate at the TOC Visit in the Clinically Evaluable (CE) Populations.		8-15 days after last dose of study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
To Evaluate the Microbiological Success Rate at the TOC Visit	8-15 days after the last dose of study drug
To Evaluate the Clinical Response at the End of Therapy (EOT) Visit	last day of study drug administration
To Evaluate the Clinical and Microbiological Response by Pathogen at the TOC Visit	8-15 days after last dose of study drug
To Evaluate Clinical Relapse at the Late Follow Up (LFU) Visit	21 to 35 days after the last dose of study drug
To Evaluate Microbiological Reinfection or Recurrence at the LFU Visit	21-35 days after last dose of study drug
To Evaluate Safety	first study drug dose through TOC

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Investigators: Principal Investigator: Mark Wilcox, MD, Old Medical School

Publications and helpful links

General Publications

• Dryden M, Kantecki M, Yan JL, Stone GG, Leister-Tebbe H, Wilcox M. Treatment outcomes of secondary bacteraemia in patients treated with ceftaroline fosamil: pooled results from six phase III clinical trials. J Glob Antimicrob Resist. 2022 Mar;28:108-114. doi: 10.1016/j.jgar.2021.10.027. Epub 2021 Dec 16.
• Cheng K, Pypstra R, Yan JL, Hammond J. Summary of the safety and tolerability of two treatment regimens of ceftaroline fosamil: 600 mg every 8 h versus 600 mg every 12 h. J Antimicrob Chemother. 2019 Apr 1;74(4):1086-1091. doi: 10.1093/jac/dky519.
• Wilcox M, Yan JL, Gonzalez PL, Dryden M, Stone GG, Kantecki M. Impact of Underlying Comorbidities on Outcomes of Patients Treated with Ceftaroline Fosamil for Complicated Skin and Soft Tissue Infections: Pooled Results from Three Phase III Randomized Clinical Trials. Infect Dis Ther. 2022 Feb;11(1):217-230. doi: 10.1007/s40121-021-00557-w. Epub 2021 Nov 6.
• Corey GR, Wilcox MH, Gonzalez J, Jandourek A, Wilson DJ, Friedland HD, Das S, Iaconis J, Dryden M. Ceftaroline fosamil therapy in patients with acute bacterial skin and skin-structure infections with systemic inflammatory signs: A retrospective dose comparison across three pivotal trials. Int J Antimicrob Agents. 2019 Jun;53(6):830-837. doi: 10.1016/j.ijantimicag.2019.01.016. Epub 2019 Feb 1.
• Corrado ML. Integrated safety summary of CANVAS 1 and 2 trials: Phase III, randomized, double-blind studies evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother. 2010 Nov;65 Suppl 4:iv67-iv71. doi: 10.1093/jac/dkq256.
• Corey GR, Wilcox M, Talbot GH, Friedland HD, Baculik T, Witherell GW, Critchley I, Das AF, Thye D. Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection. Clin Infect Dis. 2010 Sep 15;51(6):641-50. doi: 10.1086/655827.
• Wilcox MH, Corey GR, Talbot GH, Thye D, Friedland D, Baculik T; CANVAS 2 investigators. CANVAS 2: the second Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother. 2010 Nov;65 Suppl 4:iv53-iv65. doi: 10.1093/jac/dkq255.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: January 16, 2007
• First Submitted That Met QC Criteria: January 16, 2007
• First Posted (Estimate): January 18, 2007

Study Record Updates

• Last Update Posted (Actual): March 14, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Ceftaroline; Abscess; cSSSI; Staphylococcus aureus; Antibiotic; Cephalosporin; Intravenous; Prodrug; Surgical site infection; Cellulitis; Antimicrobial; Skin infection; Antibacterial; Bacterial infection, skin; Ceftaroline acetate; Methicillin-resistant Staphylococcus Aureus (MRSA); PPI-0903; Skin disease, bacterial; Staphylococcal skin infection; Streptococcal skin infection; TAK-599; Complicated skin and skin structure infection (cSSSI)
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Ceftaroline fosamil; Aztreonam
• Other Study ID Numbers: P903-07