Bacterial Infection
Conditions
Keywords
complicated skin and skin structure infections, linezolid, ceftaroline, clinical response, microbiological response, Cellulitis, Abscess, Wound infection, Deeper soft tissue, Significant surgical intervention, Gram-positive bacterial infection, Gram-negative bacterial infection, bacterial infection, cephalosporin, broad-spectrum activity
Brief summary
The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of complicated skin and skin structure infections in adults.
Detailed description
The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of complicated skin and skin structure infections in adults. The primary focus is bacterial infection.
Interventions
DRUGceftaroline
600 mg injected every 12 hours for at least 5 but not more than 14 days
DRUGlinezolid
600 mg parenteral infused over 60 minutes for a minimum of 5 days and a maximum of 14 days
DRUGAztreonam
1000 mg infused over 60 minutes every 24 hours may be started with linezolid or added later (up to 72 hours after the first dose of linezolid) for subjects with a gram-negative infection indicated.
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Complicated skin and skin structure infection (cSSSI) * Require initial hospitalization, or treatment in an emergency room or urgent care setting
Exclusion criteria
* Hypersensitivity or allergic reaction to any ß-lactam, ceftaroline, linezolid, aztreonam, or to their components * Concomitant use of adrenergic or serotonergic agent * Uncomplicated skin and skin structure infection * Concomitant therapy with any drug known to exhibit a contraindicated drug-drug interaction * More than 24 hours of treatment with an antimicrobial within 96 hours before randomization * Known or suspected endocarditis, osteomyelitis, or septic arthritis * Severely impaired renal function * Evidence of significant hepatic, hematologic, or immunologic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response at the Test of Cure (TOC) Visit in the Modified Intent-to-treat (MITT) Population | Test of Cure Visit (8 to 15 days after end of therapy) | The coprimary efficacy outcome measures were the per-subject clinical cure rate at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) and (Modified-Intent-to-Treat) MITT Populations. Subjects were considered clinically cured at the Test of Cure (TOC) Visit if they had total resolution of all signs and symptoms of the baseline infection, or improvement of the infection to such an extent that no further antimicrobial therapy was necessary. |
| Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population | Test of Cure Visit (8 to 15 Days after end of therapy) | The coprimary efficacy outcome measures were the per-subject clinical cure rate at the TOC Visit in the CE and MITT Populations. Subjects were considered clinically cured at the TOC Visit if they had total resolution of all signs and symptoms of the baseline infection, or improvement of the infection to such an extent that no further antimicrobial therapy was necessary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response at the End-of-Therapy (EOT) Visit in the MITT, cMITT and CE Populations. | End-of-therapy (EOT) visit | Evaluate per-subject the clinical response at the End-of-therapy (EOT) Visit in the MITT, cMITT and CE populations. |
| The Microbiological Response at the TOC Visit in the mMITT and ME Populations. | TOC Visit (8 to 15 days after end of therapy) | Evaluate per-subject the microbiological response at the TOC Visit in the Microbiological Modified Intent-to-treat (mMITT) and Microbiologically Evaluable (ME) populations. |
| The Safety of Ceftaroline Fosamil | First dose of study drug through LFU Visit or 30 days after the last dose of study drug | Evaluate safety of Ceftaroline fosamil IM in adults with complicated skin and skin structure infection (cSSSI) |
| Clinical Relapse at the Late Follow-up Visit | Late Follow-up (LFU) Visit (21 to 35 days after end of therapy) | Evaluate Clinical relapse rate at Late Follow-up (LFU) (21 to 45 days after the final dose of study drug)in those subjects clinically cured at the TOC visit. |
| The Microbiological Reinfection or Recurrence at the Late Follow-up (LFU) Visit | LFU Visit (21 to 35 days after end of therapy) | Evaluate per-subject reinfection or recurrence rate at the LFU Visit in those subjects who had a favorable microbiological outcome (eradication or presumed eradication) at the TOC Visit. |
| Clinical and Microbiological Response by Pathogen at the TOC Visit in the mMITT and ME Populations | TOC Visit (8 to 15 days after end of therapy) | Evaluate the clinical and microbiological response by pathogen at the TOC Visit in the mMITT and ME populations. |
| Clinical Cure Rate at the TOC Visit in the cMITT Population | TOC Visit (8 to 15 days after end of therapy) | Evaluate per-subject the clinical response at the Test-of-Cure (TOC) Visit in the Clinical Modified Intent-to-treat (cMITT) Population. |
Countries
United States
Participant flow
Recruitment details
Twelve (12) study centers in the U.S. participated in this open label trial.
Participants by arm
| Arm | Count |
|---|---|
| Ceftaroline Intramuscular every 12 hours | 103 |
| Linezolid Intravenous Linezolid every 12 hours (with or without Aztreonam) | 47 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Miscellaneous Other | 3 | 2 |
| Overall Study | Randomized, did not receive study drug | 5 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Ceftaroline | Linezolid | Total |
|---|---|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 12.83 | 39.9 years STANDARD_DEVIATION 14.58 | 39.7 years STANDARD_DEVIATION 13.36 |
| Region of Enrollment United States | 103 participants | 47 participants | 150 participants |
| Sex: Female, Male Female | 33 Participants | 18 Participants | 51 Participants |
| Sex: Female, Male Male | 70 Participants | 29 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 98 | 15 / 45 |
| serious Total, serious adverse events | 4 / 98 | 0 / 45 |
Outcome results
Primary
Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population
The coprimary efficacy outcome measures were the per-subject clinical cure rate at the TOC Visit in the CE and MITT Populations. Subjects were considered clinically cured at the TOC Visit if they had total resolution of all signs and symptoms of the baseline infection, or improvement of the infection to such an extent that no further antimicrobial therapy was necessary.
Time frame: Test of Cure Visit (8 to 15 Days after end of therapy)
Population: The Clinically Evaluable (CE) Population included all subjects who satisfied key minimum protocol criteria
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ceftaroline | Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population | 90.7 percentage of participants |
| Linezolid (With or Without Aztreonam) | Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population | 97.4 percentage of participants |
Primary
Clinical Response at the Test of Cure (TOC) Visit in the Modified Intent-to-treat (MITT) Population
The coprimary efficacy outcome measures were the per-subject clinical cure rate at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) and (Modified-Intent-to-Treat) MITT Populations. Subjects were considered clinically cured at the Test of Cure (TOC) Visit if they had total resolution of all signs and symptoms of the baseline infection, or improvement of the infection to such an extent that no further antimicrobial therapy was necessary.
Time frame: Test of Cure Visit (8 to 15 days after end of therapy)
Population: Modified-Intent-to-Treat (MITT) Population - Any randomized subjects that received any amount of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ceftaroline | Clinical Response at the Test of Cure (TOC) Visit in the Modified Intent-to-treat (MITT) Population | 84.7 percentage of participants |
| Linezolid (With or Without Aztreonam) | Clinical Response at the Test of Cure (TOC) Visit in the Modified Intent-to-treat (MITT) Population | 88.9 percentage of participants |
Secondary
Clinical and Microbiological Response by Pathogen at the TOC Visit in the mMITT and ME Populations
Evaluate the clinical and microbiological response by pathogen at the TOC Visit in the mMITT and ME populations.
Time frame: TOC Visit (8 to 15 days after end of therapy)
Secondary
Clinical Cure Rate at the TOC Visit in the cMITT Population
Evaluate per-subject the clinical response at the Test-of-Cure (TOC) Visit in the Clinical Modified Intent-to-treat (cMITT) Population.
Time frame: TOC Visit (8 to 15 days after end of therapy)
Secondary
Clinical Relapse at the Late Follow-up Visit
Evaluate Clinical relapse rate at Late Follow-up (LFU) (21 to 45 days after the final dose of study drug)in those subjects clinically cured at the TOC visit.
Time frame: Late Follow-up (LFU) Visit (21 to 35 days after end of therapy)
Secondary
Clinical Response at the End-of-Therapy (EOT) Visit in the MITT, cMITT and CE Populations.
Evaluate per-subject the clinical response at the End-of-therapy (EOT) Visit in the MITT, cMITT and CE populations.
Time frame: End-of-therapy (EOT) visit
Secondary
The Microbiological Reinfection or Recurrence at the Late Follow-up (LFU) Visit
Evaluate per-subject reinfection or recurrence rate at the LFU Visit in those subjects who had a favorable microbiological outcome (eradication or presumed eradication) at the TOC Visit.
Time frame: LFU Visit (21 to 35 days after end of therapy)
Secondary
The Microbiological Response at the TOC Visit in the mMITT and ME Populations.
Evaluate per-subject the microbiological response at the TOC Visit in the Microbiological Modified Intent-to-treat (mMITT) and Microbiologically Evaluable (ME) populations.
Time frame: TOC Visit (8 to 15 days after end of therapy)
Secondary
The Safety of Ceftaroline Fosamil
Evaluate safety of Ceftaroline fosamil IM in adults with complicated skin and skin structure infection (cSSSI)
Time frame: First dose of study drug through LFU Visit or 30 days after the last dose of study drug