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

NCT02202135 | Terminated Phase 3 Results

• 1 other identifier: D3720C00001sub
• Study Type: interventional
• Target: 4
• Locations: 13 countries
• Sites: 22

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 (1)

• Clinical Response at TOC

  Clinical cure is defined as resolution or improvement of signs and symptoms compared to baseline and no further antimicrobial therapy is necessary. Clinical failure is defined as any of the following: persistence or worsening in signs or symptoms, or requirement for concomitant antibiotic therapy, or requirement of an unplanned surgical intervention \>48 hours after the first dose, or death caused by skin infection, or an AE leading to study drug discontinuation with alternative antimicrobial therapy required, or diagnosis of osteomyelitis \>=8 days after the first dose.

  7 to 20 days after 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. patients must have a positive culture for MRSA that has been obtained from the skin infection site and/or blood samples at any time within the 72hrs before the first dose.

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 (22)

Research site

Córdoba, Argentina

Location

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Salvador, Estado de Bahia, Brazil

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Passo Fundo, Rio Grande do Sul, Brazil

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São José do Rio Preto, Brazil

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Pleven, Bulgaria

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Temuco, Chile

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Zagreb, Croatia

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Athens, Greece

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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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Lodz, Poland

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Bucharest, Romania

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Dundee, South Africa

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Worcester, South Africa

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Granada, Spain

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Terrassa, Spain

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Ankara, Turkey (Türkiye)

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Diyarbakır, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

Location

Related Publications (1)

• 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

Limitations and Caveats

Early termination leading to small number of subjects analyzed.

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: July 25, 2014
• First Posted: July 28, 2014
• Study Start: June 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: September 6, 2017
• Results First Posted: March 31, 2016

Record last verified: 2017-09

Locations

ES (2); IT (1); BR (3); BU (1); CR (1); IL (4); PL (1); RO (1); ZA (2); AR (1); TU (3); CL (1); GR (1)