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

• ClinicalTrials.gov Identifier: NCT01499277
• Recruitment Status: Completed
• First Posted: December 26, 2011
• Results First Posted: November 9, 2015
• Last Update Posted: September 6, 2017
• Sponsor: Pfizer
• Collaborator: Forest Laboratories
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Complicated Skin and Soft Tissue Infection	Drug: Ceftaroline fosamil; Drug: Vancomycin; Drug: Aztreonam	Phase 3

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 802 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: May 2012
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: January 2015

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Ceftaroline fosamil; IV ceftaroline 600mg every 8 hours
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	Drug: Vancomycin; IV vancomycin 15mg/kg every 12 hours; Drug: Aztreonam; IV aztreonam 1 g every 8 hours

Outcome Measures

Primary Outcome Measures :

1. Clinical Response at Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set [ Time Frame: 7 to 20 days after the last dose of study drug ]
   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.
2. Clinical Response at TOC in Clinically Evaluable (CE) Analysis Set [ Time Frame: 7 to 20 days after the last dose of study drug ]
   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.

Secondary Outcome Measures :

1. Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set [ Time Frame: 7 to 20 days after the last dose of study drug ]
   Difference in microbiological favorable response rate at TOC in mMITT analysis set. Favorable microbiological response rate is measured by comparing TOC microbiological data to baseline microbiological data. In the absence of TOC microbiological data it is presumed from the clinical response.
2. Per-patient Micro Response at TOC in Microbiologically Evaluable (ME) Analysis Set [ Time Frame: 7 to 20 days after the last dose of study drug ]
   Difference in microbiological favorable response rate at TOC in ME. Favourable microbiological response rate is measured by comparing TOC microbiological data to baseline microbiological data. In the absence of TOC microbiological data it is presumed from the clinical response.
3. Clinical Response at End of Treatment (EOT) in MITT Analysis Set [ Time Frame: On day of last dose of study drug (or + 1 day) ]
   The observed difference in the clinical cure rates at EOT (ceftaroline group minus vancomycin plus aztreonam group) in MITT. Clinical cure rate is measured by comparing the participant's signs and symptoms at EOT visit to those recorded at study baseline.
4. Clinical Response at EOT in CE Analysis Set [ Time Frame: On day of last dose of study drug (or +1 day) ]
   The observed difference in the clinical cure rates at EOT (ceftaroline group minus vancomycin plus aztreonam group) in CE. Clinical cure rate is measured by comparing the participant's signs and symptoms at EOT visit to those recorded at study baseline.
5. Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC [ Time Frame: 21 to 42 days after the last dose of study drug ]
   The observed difference in the clinical relapse rates at LFU (ceftaroline group minus vancomycin plus aztreonam group) in CE. Clinical relapse rate at LFU is measured by comparing a patient's signs and symptoms at late follow-up to those when they were cured at TOC.
6. Early Response at 48 to 72 Hours of Treatment in MITT Analysis Set [ Time Frame: 48 to 72 hours after first dose of study drug ]
   The observed difference in the early success rates at 48 to 72 hours of treatment (ceftaroline group minus vancomycin plus aztreonam group) in MITT. Early response rate as measured by comparing the participant's signs and symptoms at the 48-72 hour visit to those recorded at study baseline.
7. Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME [ Time Frame: 7 to 20 days after the last dose of study drug ]
   Per-pathogen microbiological response at TOC by baseline pathogen from site of skin infection in ME analysis set

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

  Hide Study Locations

Locations

United States, California

Research Site

Chula Vista, California, United States

United States, Florida

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Orlando, Florida, United States

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West Palm Beach, Florida, United States

United States, Indiana

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Carmel, Indiana, United States

United States, Kentucky

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Hazard, Kentucky, United States

United States, Massachusetts

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Springfield, Massachusetts, United States

United States, Michigan

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Detroit, Michigan, United States

United States, Nevada

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Las Vegas, Nevada, United States

United States, New York

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Garden City, New York, United States

United States, Texas

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Bellaire, Texas, United States

Argentina

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Córdoba, Argentina

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Santa Fe, Argentina

Australia

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Parkville, Australia

Belgium

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Bruxelles, Belgium

Brazil

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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

Bulgaria

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Pleven, Bulgaria

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Ruse, Bulgaria

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Sofia, Bulgaria

Chile

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Temuco, Chile

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Viña del Mar, Chile

China

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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

Croatia

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Slavonski Brod, Croatia

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Zagreb, Croatia

Czechia

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Jihlava, Czechia

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Pardubice, Czechia

France

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Orleans, France

Germany

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Dessau, Germany

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Hanau, Germany

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Heilbronn, Germany

Greece

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Athens, Greece

Hong Kong

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Kowloon, Hong Kong

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Pokfulam, Hong Kong

Israel

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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

Italy

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Milano, Italy

Korea, Republic of

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Ansan, Korea, Republic of

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Deagu, Korea, Republic of

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Incheon, Korea, Republic of

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Seoul, Korea, Republic of

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Won-ju, Korea, Republic of

Mexico

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Guadalajara, Mexico

Peru

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Cusco, Peru

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Lima, Peru

Philippines

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Manila, Philippines

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Quezon City, Philippines

Poland

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Lublin, Poland

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Łódź, Poland

Romania

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Bucharest, Romania

Russian Federation

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Moscow, Russian Federation

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Perm, Russian Federation

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Saint Petersburg, Russian Federation

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Smolensk, Russian Federation

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Vsevolozhsk, Russian Federation

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Yaroslavl, Russian Federation

South Africa

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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

Spain

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Barcelona, Spain

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Granada, Spain

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Madrid, Spain

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Terrassa, Spain

Taiwan

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Kaohsiung, Taiwan

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Taipei, Taiwan

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Yung Kang City, Taiwan

Turkey

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Ankara, Turkey

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Diyarbakir, Turkey

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Izmir, Turkey

Ukraine

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Cherkasy, Ukraine

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Ivano-Frankivsk, Ukraine

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Kharkov, Ukraine

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Odesa, Ukraine

Sponsors and Collaborators

Pfizer

Forest Laboratories

Investigators

• Study Director: David Melnick, MSD; AstraZeneca

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Epub 2016 Sep 1.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01499277 History of Changes
• Other Study ID Numbers: D3720C00001; 2011-004013-16
• First Posted: December 26, 2011
• Results First Posted: November 9, 2015
• Last Update Posted: September 6, 2017
• Last Verified: September 2017

Keywords provided by Pfizer:

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

Additional relevant MeSH terms:

Infection; Communicable Diseases; Soft Tissue Infections; Vancomycin; Ceftaroline fosamil; Cephalosporins; Aztreonam; Anti-Bacterial Agents; Anti-Infective Agents