Bacterial Infections
Conditions
Keywords
Abscess, Antibacterial, Antibiotic, Antimicrobial, Bacterial infection, skin, Ceftaroline, Ceftaroline acetate, Cellulitis, Cephalosporin, Complicated skin and skin structure infection (cSSSI), 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 this study is to compare ceftaroline effectivity versus Vancomycin plus Aztreonam in the treatment of complicated skin infections in adults.
Interventions
DRUGceftaroline
600 mg parenteral infused over 60 minutes, every 12 hours for 5 to 14 days
DRUGvancomycin plus 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.
DRUGPlacebo
Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours.
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 complicated skin and skin structure infection (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 last dose of study drug administration | 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 complicated skin and skin structure infection (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 |
| The Primary Efficacy Outcome Measure Was the Per-subject Clinical Cure Rate at the TOC Visit in the Clinically Evaluable (CE) Populations. | 8-15 days after last dose of study drug | — |
Secondary
| Measure | Time frame |
|---|---|
| To Evaluate the Microbiological Success Rate at the TOC Visit | 8-15 days after the last dose of study drug |
| To Evaluate the Clinical Response at the End of Therapy (EOT) Visit | last day of study drug administration |
| To Evaluate the Clinical and Microbiological Response by Pathogen at the TOC Visit | 8-15 days after last dose of study drug |
| To Evaluate Clinical Relapse at the Late Follow Up (LFU) Visit | 21 to 35 days after the last dose of study drug |
| To Evaluate Microbiological Reinfection or Recurrence at the LFU Visit | 21-35 days after last dose of study drug |
| To Evaluate Safety | first study drug dose through TOC |
Countries
Argentina, Austria, Brazil, Chile, Germany, Latvia, Mexico, Poland, Russia, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Patients were recruited worldwide from March 2007 to December 2007
Pre-assignment details
Patients were screened for up to 24 hours
Participants by arm
| Arm | Count |
|---|---|
| Ceftaroline for Injection Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours. | 342 |
| 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. | 338 |
| Total | 680 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Non-compliance | 0 | 1 |
| Overall Study | Other | 15 | 16 |
| Overall Study | Request of sponsor/investigator | 1 | 0 |
| Overall Study | Withdrew consent | 10 | 8 |
Baseline characteristics
| Characteristic | Total | IV Vancomycin Plus IV Aztreonam | Ceftaroline for Injection |
|---|---|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 16.52 | 47.5 years STANDARD_DEVIATION 16.07 | 47.8 years STANDARD_DEVIATION 16.98 |
| Age, Customized >18 and < 65 years | 572 participants | 291 participants | 281 participants |
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized >=65 years | 108 participants | 47 participants | 61 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 122 Participants | 59 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 558 Participants | 279 Participants | 279 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 255 Participants | 137 Participants | 118 Participants |
| Sex: Female, Male Male | 425 Participants | 201 Participants | 224 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 144 / 341 | 159 / 339 |
| serious Total, serious adverse events | 14 / 341 | 16 / 339 |
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 complicated skin and skin structure infection (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 last dose of study drug administration
Population: MITT (Modified Intent to Treat) - all subjects that received any amount of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline for Injection | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Clinical Cure | 291 participants |
| Ceftaroline for Injection | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Clinical Failure | 25 participants |
| Ceftaroline for Injection | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Indeterminate | 26 participants |
| IV Vancomycin Plus IV Aztreonam | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Clinical Cure | 289 participants |
| IV Vancomycin Plus IV Aztreonam | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Clinical Failure | 28 participants |
| IV Vancomycin Plus IV Aztreonam | Clinical Cure Rate at Test of Cure (TOC) (MITT Population) | Indeterminate | 21 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: [-5.8, 5]
Primary
The Primary Efficacy Outcome Measure Was the Per-subject Clinical Cure Rate at the TOC Visit in the Clinically Evaluable (CE) Populations.
Time frame: 8-15 days after last dose of study drug
Secondary
To Evaluate Clinical Relapse at the Late Follow Up (LFU) Visit
Time frame: 21 to 35 days after the last dose of study drug
Secondary
To Evaluate Microbiological Reinfection or Recurrence at the LFU Visit
Time frame: 21-35 days after last dose of study drug
Secondary
To Evaluate Safety
Time frame: first study drug dose through TOC
Secondary
To Evaluate the Clinical and Microbiological Response by Pathogen at the TOC Visit
Time frame: 8-15 days after last dose of study drug
Secondary
To Evaluate the Clinical Response at the End of Therapy (EOT) Visit
Time frame: last day of study drug administration
Secondary
To Evaluate the Microbiological Success Rate at the TOC Visit
Time frame: 8-15 days after the last dose of study drug