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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01499277




Registration number
NCT01499277
Ethics application status
Date submitted
16/12/2011
Date registered
26/12/2011
Date last updated
6/09/2017

Titles & IDs
Public title
Evaluation of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam in the Treatment of Patients With Skin Infections
Scientific 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
Secondary ID [1] 0 0
2011-004013-16
Secondary ID [2] 0 0
D3720C00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Complicated Skin and Soft Tissue Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ceftaroline fosamil
Treatment: Drugs - Vancomycin
Treatment: Drugs - Aztreonam

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.

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


Treatment: Drugs: Ceftaroline fosamil
IV ceftaroline 600mg every 8 hours

Treatment: Drugs: Vancomycin
IV vancomycin 15mg/kg every 12 hours

Treatment: Drugs: Aztreonam
IV aztreonam 1 g every 8 hours
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Clinical Response at Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set
Timepoint [1] 0 0
7 to 20 days after the last dose of study drug
Primary outcome [2] 0 0
Clinical Response at TOC in Clinically Evaluable (CE) Analysis Set
Timepoint [2] 0 0
7 to 20 days after the last dose of study drug
Secondary outcome [1] 0 0
Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set
Timepoint [1] 0 0
7 to 20 days after the last dose of study drug
Secondary outcome [2] 0 0
Per-patient Micro Response at TOC in Microbiologically Evaluable (ME) Analysis Set
Timepoint [2] 0 0
7 to 20 days after the last dose of study drug
Secondary outcome [3] 0 0
Clinical Response at End of Treatment (EOT) in MITT Analysis Set
Timepoint [3] 0 0
On day of last dose of study drug (or + 1 day)
Secondary outcome [4] 0 0
Clinical Response at EOT in CE Analysis Set
Timepoint [4] 0 0
On day of last dose of study drug (or +1 day)
Secondary outcome [5] 0 0
Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC
Timepoint [5] 0 0
21 to 42 days after the last dose of study drug
Secondary outcome [6] 0 0
Early Response at 48 to 72 Hours of Treatment in MITT Analysis Set
Timepoint [6] 0 0
48 to 72 hours after first dose of study drug
Secondary outcome [7] 0 0
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME
Timepoint [7] 0 0
7 to 20 days after the last dose of study drug

Eligibility
Key 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
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2015
Sample size
Target
Accrual to date
Final
802
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
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United States of America
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Nevada
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United States of America
State/province [8] 0 0
New York
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United States of America
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Texas
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Argentina
State/province [10] 0 0
Córdoba
Country [11] 0 0
Argentina
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Santa Fe
Country [12] 0 0
Belgium
State/province [12] 0 0
Bruxelles
Country [13] 0 0
Brazil
State/province [13] 0 0
Belo Horizonte
Country [14] 0 0
Brazil
State/province [14] 0 0
Passo Fundo
Country [15] 0 0
Brazil
State/province [15] 0 0
Salvador
Country [16] 0 0
Brazil
State/province [16] 0 0
São José do Rio Preto
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Pleven
Country [18] 0 0
Bulgaria
State/province [18] 0 0
Ruse
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Sofia
Country [20] 0 0
Chile
State/province [20] 0 0
Temuco
Country [21] 0 0
Chile
State/province [21] 0 0
Viña del Mar
Country [22] 0 0
China
State/province [22] 0 0
Beijing
Country [23] 0 0
China
State/province [23] 0 0
Changchun
Country [24] 0 0
China
State/province [24] 0 0
Changsha
Country [25] 0 0
China
State/province [25] 0 0
Chengdu
Country [26] 0 0
China
State/province [26] 0 0
Chongqing
Country [27] 0 0
China
State/province [27] 0 0
Fuzhou
Country [28] 0 0
China
State/province [28] 0 0
Guangzhou
Country [29] 0 0
China
State/province [29] 0 0
Haikou
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China
State/province [30] 0 0
Nanning
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China
State/province [31] 0 0
Qingdao
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China
State/province [32] 0 0
Shanghai
Country [33] 0 0
China
State/province [33] 0 0
Shenyang
Country [34] 0 0
China
State/province [34] 0 0
Shijiazhuang
Country [35] 0 0
China
State/province [35] 0 0
Wuhan
Country [36] 0 0
China
State/province [36] 0 0
Xi'an
Country [37] 0 0
Croatia
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Slavonski Brod
Country [38] 0 0
Croatia
State/province [38] 0 0
Zagreb
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Czechia
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Jihlava
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Czechia
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Pardubice
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France
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Orleans
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Germany
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Dessau
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Germany
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Hanau
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Germany
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Heilbronn
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Greece
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Athens
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Hong Kong
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Kowloon
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Hong Kong
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Pokfulam
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Israel
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Haifa
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Israel
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Ramat-Gan
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Israel
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Safed
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Israel
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Tel Aviv
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Italy
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Milano
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Korea, Republic of
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Ansan
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Korea, Republic of
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Deagu
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Korea, Republic of
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Won-ju
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Mexico
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Guadalajara
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Peru
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Cusco
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Peru
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Lima
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Philippines
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Manila
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Philippines
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Quezon City
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Poland
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Lublin
Country [64] 0 0
Poland
State/province [64] 0 0
Lódz
Country [65] 0 0
Romania
State/province [65] 0 0
Bucharest
Country [66] 0 0
Russian Federation
State/province [66] 0 0
Moscow
Country [67] 0 0
Russian Federation
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Perm
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Russian Federation
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Saint Petersburg
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Russian Federation
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Smolensk
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Russian Federation
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Vsevolozhsk
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Russian Federation
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Yaroslavl
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South Africa
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Benoni
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South Africa
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Cape Town
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South Africa
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Johannesburg
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South Africa
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Worcester
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Spain
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Barcelona
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Spain
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Granada
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Spain
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Madrid
Country [79] 0 0
Spain
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Terrassa
Country [80] 0 0
Taiwan
State/province [80] 0 0
Kaohsiung
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Taiwan
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Taipei
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Taiwan
State/province [82] 0 0
Yung Kang City
Country [83] 0 0
Turkey
State/province [83] 0 0
Ankara
Country [84] 0 0
Turkey
State/province [84] 0 0
Diyarbakir
Country [85] 0 0
Turkey
State/province [85] 0 0
Izmir
Country [86] 0 0
Ukraine
State/province [86] 0 0
Cherkasy
Country [87] 0 0
Ukraine
State/province [87] 0 0
Ivano-Frankivsk
Country [88] 0 0
Ukraine
State/province [88] 0 0
Kharkov
Country [89] 0 0
Ukraine
State/province [89] 0 0
Odesa

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Forest Laboratories
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01499277
Trial related presentations / 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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
David Melnick, MSD
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01499277