Bacterial Infections
Conditions
Keywords
Abscess, Antibacterial, Antibiotic, Antimicrobial, Bacterial infection, skin, Ceftaroline, Ceftaroline acetate, Cellulitis, Cephalosporin, Complicated skin and skin structure infection, cSSSI, Intravenous, Methicillin-resistant Staphylococcus Aureus (MRSA), PPI-0903, Prodrug, Skin disease, bacterial, Skin infection, Staphylococcal skin infection, Staphylococcus aureus, Streptococcal skin infection, Surgical site infection, TAK-599
Brief summary
The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of complicated skin infections in adults.
Detailed description
Additional purpose of the study is to compare ceftaroline effectivity versus Vancomycin plus Aztreonam in the treatment of complicated skin infections in adults.
Interventions
DRUGIV Vancomycin plus IV Aztreonam
vancomycin at 1 g parenteral infused over 60 minutes followed by aztreonam 1 g infused over 60 minutes, every 12 hours, for 5 to 14 days.
DRUGCeftaroline
600 mg parenteral infused over 60 minutes, every 12 hours for 5 to 14 days
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Skin and skin structure infection (SSSI) that involves deeper soft tissue or requires significant surgical intervention, or cellulitis or abscess on lower extremity which occurs in subjects with diabetes mellitus or well-documented peripheral vascular disease.
Exclusion criteria
* Prior treatment of current cSSSI with an antimicrobial. * Failure of vancomycin or aztreonam as therapy for the current cSSSI, or prior isolation of an organism with in vitro resistance to vancomycin or aztreonam.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | 8-15 days after the end of treatment | Cure: Total resolution of all signs and symptoms of the baseline infection, or improvement of the infection such that no further antimicrobial therapy was necessary. Failure: Requirement of alternative antimicrobial therapy for primary infection of cSSSI due to inadequate response, recurrence, new infection at the same site; treatment-limiting adverse event (AE); requirement for surgery due to failure of study drug; diagnosis of osteomyelitis after Study Day 8; or death caused by cSSSI. Indeterminate: Inability to determine an outcome |
| Clinical Cure Rate of Ceftaroline Compared With That of Vancomycin Plus Aztreonam Treatment at TOC in the Clinically Evaluable (CE) Population | 8-15 days after last dose of study drug | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical and Microbiological Response by Pathogen at the TOC Visit | 8-15 days after last dose of study drug | — |
| Clinical Relapse at the Late Follow Up (LFU) Visit | 21 to 35 days after the last dose of study drug | — |
| Microbiological Success Rate at the TOC Visit | 8-15 days after last dose of study drug | — |
| Assess Safety | First dose of study drug through TOC visit | Comparisons of the number of participants with Adverse Events |
| Microbiological Reinfection or Recurrence at the LFU Visit | 21 to 35 days after the last dose of study drug | — |
| Clinical Response at the End of Therapy (EOT) Visit | Last day of study drug administration | — |
Countries
Argentina, Brazil, Chile, Germany, Mexico, Peru, Poland, Romania, Russia, Ukraine, United States
Participant flow
Recruitment details
Patients were recruited worldwide from February 2007 to November 2007
Pre-assignment details
Patients were screened for up to 24 hours
Participants by arm
| Arm | Count |
|---|---|
| Ceftaroline Fosamil for Injection Ceftaroline fosamil 600 mg administered IV over 60 minutes every 12 hours followed by placebo administered over 60 minutes every 12 hours | 351 |
| IV Vancomycin Plus IV Aztreonam Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours | 347 |
| Total | 698 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 0 |
| Overall Study | Diagnosis of osteomyelitis | 0 | 1 |
| Overall Study | Noncompliance | 1 | 2 |
| Overall Study | Other | 15 | 21 |
| Overall Study | Request of sponsor or investigator | 0 | 2 |
| Overall Study | Withdrew consent | 3 | 4 |
Baseline characteristics
| Characteristic | Ceftaroline Fosamil for Injection | IV Vancomycin Plus IV Aztreonam | Total |
|---|---|---|---|
| Age, Continuous | 49.2 years STANDARD_DEVIATION 17.17 | 47.2 years STANDARD_DEVIATION 17.01 | 48.2 years STANDARD_DEVIATION 17.1 |
| Age, Customized <18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized >=18 years and < 65 years | 294 participants | 275 participants | 569 participants |
| Age, Customized >=65 years | 57 participants | 72 participants | 129 participants |
| Race/Ethnicity, Customized Hispanic | 83 participants | 77 participants | 160 participants |
| Race/Ethnicity, Customized Non-Hispanic | 268 participants | 270 participants | 538 participants |
| Sex: Female, Male Female | 131 Participants | 129 Participants | 260 Participants |
| Sex: Female, Male Male | 220 Participants | 218 Participants | 438 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 128 / 351 | 162 / 347 |
| serious Total, serious adverse events | 16 / 351 | 12 / 347 |
Outcome results
Primary
Clinical Cure Rate at Test of Cure (TOC) (MITT Population)
Cure: Total resolution of all signs and symptoms of the baseline infection, or improvement of the infection such that no further antimicrobial therapy was necessary. Failure: Requirement of alternative antimicrobial therapy for primary infection of cSSSI due to inadequate response, recurrence, new infection at the same site; treatment-limiting adverse event (AE); requirement for surgery due to failure of study drug; diagnosis of osteomyelitis after Study Day 8; or death caused by cSSSI. Indeterminate: Inability to determine an outcome
Time frame: 8-15 days after the end of treatment
Population: MITT (Modified Intent to Treat) - Any randomized subjects that received any amount of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline Fosamil for Injection | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Clinical Cure | 304 participants |
| Ceftaroline Fosamil for Injection | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Clinical Failure | 29 participants |
| Ceftaroline Fosamil for Injection | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Indeterminate | 18 participants |
| IV Vancomycin Plus IV Aztreonam | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Clinical Cure | 297 participants |
| IV Vancomycin Plus IV Aztreonam | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Clinical Failure | 21 participants |
| IV Vancomycin Plus IV Aztreonam | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Indeterminate | 29 participants |
Comparison: The primary objective of this study was to determine the noninferiority in clinical cure rate of ceftaroline in comparison with vancomycin plus aztreonam in adult subjects with cSSSI.95% CI: [-4.2, 6.2]
Primary
Clinical Cure Rate of Ceftaroline Compared With That of Vancomycin Plus Aztreonam Treatment at TOC in the Clinically Evaluable (CE) Population
Time frame: 8-15 days after last dose of study drug
Secondary
Assess Safety
Comparisons of the number of participants with Adverse Events
Time frame: First dose of study drug through TOC visit
Secondary
Clinical and Microbiological Response by Pathogen at the TOC Visit
Time frame: 8-15 days after last dose of study drug
Secondary
Clinical Relapse at the Late Follow Up (LFU) Visit
Time frame: 21 to 35 days after the last dose of study drug
Secondary
Clinical Response at the End of Therapy (EOT) Visit
Time frame: Last day of study drug administration
Secondary
Microbiological Reinfection or Recurrence at the LFU Visit
Time frame: 21 to 35 days after the last dose of study drug
Secondary
Microbiological Success Rate at the TOC Visit
Time frame: 8-15 days after last dose of study drug