Bacterial Pneumonia
Conditions
Keywords
ceftaroline, Community-acquired pneumonia, CAP, IV (intravenous), Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila spp, Legionella spp, Multi-drug resistant Streptococcus pneumoniae (MDRSP), antimicrobial resistance, pneumococci, Ceftriaxone, bacteria, ß-lactam, beta-lactam, antibiotic
Brief summary
The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of Community-Acquired Pneumonia
Detailed description
The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of Community-Acquired Pneumonia. Clinical trials for this study is held in many countries
Interventions
DRUGIV Ceftriaxone
1 g dose parenteral infused over 30 minutes, every 24 hours, for 5 to 7 days
2 consecutive, 300 mg dose parenteral infused over 30 minutes, every 12 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
DRUGClarithromycin
In both treatment groups, two doses of oral clarithromycin (500 mg q12h), defined as adjunctive therapy, were initiated on Study Day 1 with study drug therapy in order to provide an immunomodulatory benefit and initial therapy for possible infection due to an atypical organism.
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 are required to meet the following inclusion criteria: * Community-acquired pneumonia * initial hospitalization, or treatment in an emergency room or urgent care setting * infection would require initial treatment with IV antimicrobials.
Exclusion criteria
Subjects must NOT meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations | 8 to 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 to That for Ceftriaxone at Test-of-Cure (TOC) in the Clinically Evaluable (CE) Population | 8-15 days after last dose of study drug | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) | 8-15 days after last day 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 |
| Microbiological Re-infection/Recurrence at LFU | 21 to 35 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) | 21-35 days after last dose of study drug |
| Microbiological Success Rate at Test of Cure (TOC) | 8-15 days after last dose of study drug |
Countries
Argentina, Austria, Brazil, Bulgaria, Estonia, France, Georgia, Germany, Hungary, India, Lithuania, Malaysia, Poland, Romania, Russia, Serbia, Slovakia, South Africa, Spain, Switzerland, Thailand, Ukraine, United States
Participant flow
Recruitment details
The enrollment period was from 02 January 2008 to 29 December 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) | 299 |
| 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 | 606 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | At the request of sponsor/investigator | 1 | 0 |
| Overall Study | Death | 6 | 6 |
| Overall Study | Lost to Follow-up | 8 | 10 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrew consent | 9 | 6 |
Baseline characteristics
| Characteristic | Total | IV Ceftriaxone | Ceftaroline Fosamil for Injection |
|---|---|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 16.6 | 61.0 years STANDARD_DEVIATION 16.6 | 61.0 years STANDARD_DEVIATION 16.6 |
| Age, Customized <65 years | 311 participants | 157 participants | 154 participants |
| Age, Customized >= 65 years | 295 participants | 150 participants | 145 participants |
| Race/Ethnicity, Customized Hispanic | 56 participants | 27 participants | 29 participants |
| Race/Ethnicity, Customized Non-Hispanic | 550 participants | 280 participants | 270 participants |
| Sex: Female, Male Female | 220 Participants | 112 Participants | 108 Participants |
| Sex: Female, Male Male | 386 Participants | 195 Participants | 191 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 65 / 298 | 53 / 308 |
| serious Total, serious adverse events | 28 / 298 | 33 / 308 |
Outcome results
Primary
Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations
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 to 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 at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations | Clinical Cure | 244 participants |
| Ceftaroline Fosamil for Injection | Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations | Clinical Failure | 34 participants |
| Ceftaroline Fosamil for Injection | Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations | Indeterminate | 13 participants |
| IV Ceftriaxone | Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations | Clinical Cure | 233 participants |
| IV Ceftriaxone | Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations | Clinical Failure | 58 participants |
| IV Ceftriaxone | Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations | Indeterminate | 9 participants |
Comparison: The primary objective of this study was to determine the noninferiority in the clinical cure rate for ceftaroline compared to that for ceftriaxone at TOC in the CE and MITTE Populations in adult subjects with CABP.95% CI: [-0.2, 12.6]
Primary
Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test-of-Cure (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)
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 Re-infection/Recurrence at LFU
Time frame: 21 to 35 days after last dose of study drug
Secondary
Microbiological Success Rate at Test of Cure (TOC)
Time frame: 8-15 days after last dose of study drug
Secondary
Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC)
Time frame: 8-15 days after last day of study drug