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

NCT01499277 | Completed Phase 3 Results

• 2 other identifiers: D3720C000012011-004013-16
• Study Type: interventional
• Target: 802
• Locations: 28 countries
• Sites: 91

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.

Conditions

Complicated Skin and Soft Tissue Infection

Keywords

complicated skin and soft tissue infections (cSSTI); skin infection; ceftaroline; wound infection; cellulitis; burn infection; bacterial infection; vancomycin

Outcome Measures

Primary Outcomes (2)

• Clinical Response at Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set

  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.

  7 to 20 days after the last dose of study drug

• Clinical Response at TOC in Clinically Evaluable (CE) Analysis Set

  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.

  7 to 20 days after the last dose of study drug

Secondary Outcomes (7)

• Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set

  7 to 20 days after the last dose of study drug

• Per-patient Micro Response at TOC in Microbiologically Evaluable (ME) Analysis Set

  7 to 20 days after the last dose of study drug

• Clinical Response at End of Treatment (EOT) in MITT Analysis Set

  On day of last dose of study drug (or + 1 day)

• Clinical Response at EOT in CE Analysis Set

  On day of last dose of study drug (or +1 day)

• Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC

  21 to 42 days after the last dose of study drug

Study Arms (2)

Ceftaroline fosamil

EXPERIMENTAL

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

Vancomycin plus aztreonam

ACTIVE COMPARATOR

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; Drug: Aztreonam

Interventions

Ceftaroline fosamil DRUG

IV ceftaroline 600mg every 8 hours

Ceftaroline fosamil

Vancomycin DRUG

IV vancomycin 15mg/kg every 12 hours

Vancomycin plus aztreonam

Aztreonam DRUG

IV aztreonam 1 g every 8 hours

Vancomycin plus aztreonam

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead
• Forest Laboratories: collaborator

Study Sites (91)

Research Site

Chula Vista, California, United States

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Orlando, Florida, United States

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West Palm Beach, Florida, United States

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Carmel, Indiana, United States

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Hazard, Kentucky, United States

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Springfield, Massachusetts, United States

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Detroit, Michigan, United States

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Las Vegas, Nevada, United States

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Garden City, New York, United States

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Bellaire, Texas, United States

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Córdoba, Argentina

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Santa Fe, Argentina

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Parkville, Australia

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Brussels, Belgium

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Belo Horizonte, Brazil

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Passo Fundo, Brazil

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Salvador, Brazil

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São José do Rio Preto, Brazil

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Pleven, Bulgaria

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Rousse, Bulgaria

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Sofia, Bulgaria

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Temuco, Chile

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Viña del Mar, Chile

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Beijing, China

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Changchun, China

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Changsha, China

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Chengdu, China

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Chongqing, China

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Fuzhou, China

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Guangzhou, China

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Haikou, China

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Nanning, China

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Qingdao, China

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Shanghai, China

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Shenyang, China

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Shijiazhuang, China

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Wuhan, China

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Xi'an, China

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Slavonski Brod, Croatia

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Zagreb, Croatia

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Jihlava, Czechia

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Pardubice, Czechia

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Orléans, France

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Dessau, Germany

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Hanau, Germany

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Heilbronn, Germany

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Athens, Greece

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Kowloon, Hong Kong

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Pokfulam, Hong Kong

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Haifa, Israel

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Ramat Gan, Israel

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Safed, Israel

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Tel Aviv, Israel

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Milan, Italy

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Guadalajara, Mexico

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Cusco, Peru

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Lima, Peru

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Manila, Philippines

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Quezon City, Philippines

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Lodz, Poland

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Lublin, Poland

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Bucharest, Romania

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Moscow, Russia

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Perm, Russia

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Saint Petersburg, Russia

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Smolensk, Russia

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Vsevolozhsk, Russia

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Yaroslavl, Russia

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Benoni, South Africa

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Cape Town, South Africa

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Johannesburg, South Africa

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Worcester, South Africa

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Ansan, South Korea

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Deagu, South Korea

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Incheon, South Korea

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Seoul, South Korea

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Wŏnju, South Korea

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Barcelona, Spain

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Granada, Spain

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Madrid, Spain

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Terrassa, Spain

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Kaohsiung City, Taiwan

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Taipei, Taiwan

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Yung Kang City, Taiwan

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Ankara, Turkey (Türkiye)

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Diyarbakır, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

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Cherkasy, Ukraine

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Ivano-Frankivsk, Ukraine

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Kharkiv, Ukraine

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Odesa, Ukraine

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Related Publications (7)

• 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.

  PMID: 34922058 DERIVED

• 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.

  PMID: 34741280 DERIVED

• Sanchez-Garcia M, Hammond J, Yan JL, Kantecki M, Ansari W, Dryden M. Baseline Characteristics and Outcomes Among Patients with Complicated Skin and Soft Tissue Infections Admitted to the Intensive Care Unit: Analysis of the Phase 3 COVERS Randomized Trial of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam. Infect Dis Ther. 2020 Sep;9(3):609-623. doi: 10.1007/s40121-020-00297-3. Epub 2020 Jun 30.

  PMID: 32607967 DERIVED

• 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.

  PMID: 30716446 DERIVED

• 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.

  PMID: 30597021 DERIVED

• Das S, Li J, Iaconis J, Zhou D, Stone GG, Yan JL, Melnick D. Ceftaroline fosamil doses and breakpoints for Staphylococcus aureus in complicated skin and soft tissue infections. J Antimicrob Chemother. 2019 Feb 1;74(2):425-431. doi: 10.1093/jac/dky439.

  PMID: 30380060 DERIVED

• Dryden M, Zhang Y, Wilson D, Iaconis JP, Gonzalez J. A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities. J Antimicrob Chemother. 2016 Dec;71(12):3575-3584. doi: 10.1093/jac/dkw333. Epub 2016 Sep 1.

  PMID: 27585969 DERIVED

MeSH Terms

Conditions

Soft Tissue Infections; Cellulitis; Wound Infection; Bacterial Infections

Interventions

Ceftaroline; Vancomycin; Aztreonam

Condition Hierarchy (Ancestors)

Infections; Skin Diseases, Infectious; Suppuration; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Monobactams; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Yunxia Lu
• Organization: AstraZeneca-PPD

Yunxia.Lu@ppdi.com

910-558-4197

Study Officials

• David Melnick, MSD

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2011
• First Posted: December 26, 2011
• Study Start: May 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: January 1, 2015
• Last Updated: September 6, 2017
• Results First Posted: November 9, 2015

Record last verified: 2017-09

Locations

ES (4); CR (2); DE (3); BU (3); AU (1); IL (4); PL (2); RO (1); ME (1); PH (2); BR (4); KR (5); CN (15); CL (2); IT (1); RU (6); ZA (4); PE (2); GR (1); FR (1); TW (3); US (10); HK (2); BE (1); AR (2); TU (3); CZ (2); UA (4)