Bacterial Pneumonia
Conditions
Keywords
ceftaroline, Community-acquired pneumonia, CAP, Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila spp, Legionella ssp, multi-drug resistant Streptococcus pneumoniae (MDRSP), antimicrobial resistance, pneumococci, beta-lactam, ceftaroline fosamil, ceftriaxone, antibiotic
Brief summary
The purpose of the study is to determine if the antibiotic ceftaroline is safe and effective in the treatment of community-acquired pneumonia in adults.
Detailed description
Clinical trials is being held in different countries. The purpose of the study is to determine if the antibiotic ceftaroline is safe and effective in the treatment of community-acquired pneumonia in adults.
Interventions
2 consecutive, 300 mg dose parenteral infused over 30 minutes, every 12 hours for 5 to 7 days
DRUGCeftriaxone
1 g dose parenteral infused over 30 minutes, every 24 hours for 5 to 7 days
DRUGPlacebo
Subjects randomized to receive ceftriaxone will receive ceftriaxone at a dose of 1 g infused over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h). Twelve hours after each dose of ceftriaxone and saline placebo (ie, between ceftriaxone doses), subjects in this group will receive two consecutive saline placebo infusions, each infused over 30 minutes q24h. The ceftriaxone and saline placebo infusions will correspond to the q12h infusions of ceftaroline, thereby maintaining the blind
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
Subjects with community-acquired pneumonia requiring: * initial hospitalization or treatment in an emergency room or urgent care setting * infection requiring initial treatment with IV antimicrobial
Exclusion criteria
* Community-acquired pneumonia suitable for outpatient therapy with an oral antimicrobial agent * Respiratory tract infections not due to community-acquired bacterial pathogens * Infections resistant to ceftriaxone * Any condition requiring concomitant systemic corticosteroids * History of any hypersensitivity or allergic reaction to any ß-lactam antimicrobial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at the Test of Cure (TOC) in the Modified Intent to Treat Efficacy (MITTE) Population | 8-15 days after last dose of study drug | Cure:Total resolution of all signs and symptoms of pneumonia (ie,CABP), or improvement to such an extent that further antimicrobial therapy was not necessary Failure: Any of the following: * Persistence, incomplete clinical resolution, or worsening in signs and symptoms of CABP that required alternative antimicrobial therapy * Treatment-limiting adverse event (AE) leading to discontinuation of study drug therapy, when subject required alternative antimicrobial therapy to treat the pneumonia * Death wherein pneumonia (ie,CABP) was considered causative Indeterminate: Inability to determine an outcome |
| Clinical Cure Rate for Ceftaroline Compared With That for Ceftriaxone at TOC in the Clinically Evaluable (CE) Population | 8-15 days after last dose of study drug | — |
Secondary
| Measure | Time frame |
|---|---|
| Microbiological Success Rate at TOC | 8-15 days after last dose of study drug |
| Overall Clinical and Radiographic Success Rate at TOC | 8-15 days after last dose of study drug |
| Evaluate Safety | first dose, throughout the treatment period, and up to the TOC visit |
| Clinical Relapse at Late Follow Up (LFU) Visit | 21-35 days after last dose of study drug |
| Microbiological Reinfection/Recurrence at LFU | 21 to 35 days after last dose of study drug |
| Clinical and Microbiological Response by Pathogen at TOC | 8-15 days after last dose of study drug |
| Clinical Response at End of Therapy (EOT) | Last day of study drug administration |
Countries
Argentina, Austria, Bulgaria, Chile, Germany, Hungary, India, Latvia, Mexico, Peru, Poland, Romania, Russia, Ukraine, United States
Participant flow
Recruitment details
Patients were recruited worldwide from July 2007 to August 2008
Pre-assignment details
Patients were screened for up to 24 hours
Participants by arm
| Arm | Count |
|---|---|
| Ceftaroline Fosamil for Injection Ceftaroline fosamil was administered in two consecutive 300 mg IV infusions over 30 minutes, every 12 hours (q12h). | 315 |
| IV Ceftriaxone Ceftriaxone was administered as a 1-g IV infusion over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h). | 307 |
| Total | 622 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | At the request of sponsor/investigator | 1 | 2 |
| Overall Study | Death | 6 | 6 |
| Overall Study | Lost to Follow-up | 16 | 10 |
| Overall Study | Noncompliance | 0 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrew consent | 4 | 8 |
Baseline characteristics
| Characteristic | Total | IV Ceftriaxone | Ceftaroline Fosamil for Injection |
|---|---|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 16.3 | 60.0 years STANDARD_DEVIATION 15.5 | 59.0 years STANDARD_DEVIATION 17 |
| Age, Customized <65 years | 356 participants | 173 participants | 183 participants |
| Age, Customized >=65 years | 266 participants | 134 participants | 132 participants |
| Sex: Female, Male Female | 231 Participants | 105 Participants | 126 Participants |
| Sex: Female, Male Male | 391 Participants | 202 Participants | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 67 / 315 | 49 / 307 |
| serious Total, serious adverse events | 41 / 315 | 39 / 307 |
Outcome results
Primary
Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at the Test of Cure (TOC) in the Modified Intent to Treat Efficacy (MITTE) Population
Cure:Total resolution of all signs and symptoms of pneumonia (ie,CABP), or improvement to such an extent that further antimicrobial therapy was not necessary Failure: Any of the following: * Persistence, incomplete clinical resolution, or worsening in signs and symptoms of CABP that required alternative antimicrobial therapy * Treatment-limiting adverse event (AE) leading to discontinuation of study drug therapy, when subject required alternative antimicrobial therapy to treat the pneumonia * Death wherein pneumonia (ie,CABP) was considered causative Indeterminate: Inability to determine an outcome
Time frame: 8-15 days after last dose of study drug
Population: The MITTE Population consisted of all subjects in the MITT Population (all randomized subjects who received any amount of the study drug) in PORT Risk Class III or IV. The Pneumonia Outcomes Research Team (PORT) scale of CAP severity in which Risk Class I is associated with the lowest risk for mortality and Risk Class V represents the highest risk.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline Fosamil for Injection | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at the Test of Cure (TOC) in the Modified Intent to Treat Efficacy (MITTE) Population | Clinical cure | 235 participants |
| Ceftaroline Fosamil for Injection | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at the Test of Cure (TOC) in the Modified Intent to Treat Efficacy (MITTE) Population | Clinical failure | 47 participants |
| Ceftaroline Fosamil for Injection | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at the Test of Cure (TOC) in the Modified Intent to Treat Efficacy (MITTE) Population | Indeterminate | 7 participants |
| IV Ceftriaxone | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at the Test of Cure (TOC) in the Modified Intent to Treat Efficacy (MITTE) Population | Clinical cure | 206 participants |
| IV Ceftriaxone | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at the Test of Cure (TOC) in the Modified Intent to Treat Efficacy (MITTE) Population | Clinical failure | 56 participants |
| IV Ceftriaxone | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at the Test of Cure (TOC) in the Modified Intent to Treat Efficacy (MITTE) Population | Indeterminate | 11 participants |
Comparison: The primary objective of this study was to determine the noninferiority in the clinical cure rate for ceftaroline compared with that for ceftriaxone at TOC in the MITTE Population in adult subjects with CABP.95% CI: [-1, 12.7]
Primary
Clinical Cure Rate for Ceftaroline Compared With That for Ceftriaxone at TOC in the Clinically Evaluable (CE) Population
Time frame: 8-15 days after last dose of study drug
Secondary
Clinical and Microbiological Response by Pathogen at TOC
Time frame: 8-15 days after last dose of study drug
Secondary
Clinical Relapse at Late Follow Up (LFU) Visit
Time frame: 21-35 days after last dose of study drug
Secondary
Clinical Response at End of Therapy (EOT)
Time frame: Last day of study drug administration
Secondary
Evaluate Safety
Time frame: first dose, throughout the treatment period, and up to the TOC visit
Secondary
Microbiological Reinfection/Recurrence at LFU
Time frame: 21 to 35 days after last dose of study drug
Secondary
Microbiological Success Rate at TOC
Time frame: 8-15 days after last dose of study drug
Secondary
Overall Clinical and Radiographic Success Rate at TOC
Time frame: 8-15 days after last dose of study drug