Clinical trial NCT01499277: Evaluation of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam in the Treatment of Patients With Skin Infections
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Forest Laboratories
First posted: 2011-12-26
Enrollment: 802
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Clinical Response at Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set
timeFrame: 7 to 20 days after the last dose of study drug
measure: Clinical Response at TOC in Clinically Evaluable (CE) Analysis Set
timeFrame: 7 to 20 days after the last dose of study drug
Secondary outcomes:
measure: Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set
timeFrame: 7 to 20 days after the last dose of study drug
measure: Per-patient Micro Response at TOC in Microbiologically Evaluable (ME) Analysis Set
timeFrame: 7 to 20 days after the last dose of study drug
measure: Clinical Response at End of Treatment (EOT) in MITT Analysis Set
timeFrame: On day of last dose of study drug (or + 1 day)
measure: Clinical Response at EOT in CE Analysis Set
timeFrame: On day of last dose of study drug (or +1 day)
measure: Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC
timeFrame: 21 to 42 days after the last dose of study drug
measure: Early Response at 48 to 72 Hours of Treatment in MITT Analysis Set
timeFrame: 48 to 72 hours after first dose of study drug
measure: Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME
timeFrame: 7 to 20 days after the last dose of study drug
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Orlando
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Carmel
country: United States
facility: Research Site
state: Indiana
city: Hazard
country: United States
facility: Research Site
state: Kentucky
city: Springfield
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Garden City
country: United States
facility: Research Site
state: New York
city: Bellaire
country: United States
facility: Research Site
state: Texas
city: Córdoba
country: Argentina
facility: Research Site
city: Santa Fe
country: Argentina
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Passo Fundo
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Viña del Mar
country: Chile
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Slavonski Brod
country: Croatia
facility: Research Site
city: Zagreb
country: Croatia
facility: Research Site
city: Jihlava
country: Czechia
facility: Research Site
city: Pardubice
country: Czechia
facility: Research Site
city: Orleans
country: France
facility: Research Site
city: Dessau
country: Germany
facility: Research Site
city: Hanau
country: Germany
facility: Research Site
city: Heilbronn
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Kowloon
country: Hong Kong
facility: Research Site
city: Pokfulam
country: Hong Kong
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Ramat-Gan
country: Israel
facility: Research Site
city: Safed
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Ansan
country: Korea, Republic of
facility: Research Site
city: Deagu
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Won-ju
country: Korea, Republic of
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Cusco
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Smolensk
country: Russian Federation
facility: Research Site
city: Vsevolozhsk
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Benoni
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Worcester
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Terrassa
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Yung Kang City
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Diyarbakir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Cherkasy
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kharkov
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: David Melnick, MSD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.