Community-Acquired Bacterial Pneumonia, Lung Infection of Individual Not Recently Hospitalized
Conditions
Keywords
Community-Acquired Bacterial Pneumonia
Brief summary
This purpose of this study is to Evaluate the Efficacy and Safety of Intravenous Ceftaroline Versus Intravenous Ceftriaxone in the Treatment of Adult Hospitalised Patients With Community-Acquired Bacterial Pneumonia in Asia.
Interventions
DRUGCeftaroline
Two consecutive infusions q12h for 5 to 7 days
DRUGCeftriaxone
One dose infusion followed by IV saline placebo infused q24h for 5 to 7 days plus two consecutive saline placebo infusion q24h.
Sponsors
Forest Laboratories
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 150 Years
Healthy volunteers
No
Inclusion criteria
* Males and females 18 or more years of age * Lung Infection of Individual not Recently Hospitalized meeting the following criteria: Radiographically-confirmed pneumonia (new or progressive infection site of the lungs) consistent with bacterial pneumonia), AND Acute illness (≤ 7 days duration) with at least three of the following clinical signs or symptoms consistent with lung infection: New or increased cough, Purulent sputum or change in sputum character, Auscultatory findings consistent with pneumonia, Difficulty in breathing, short breath, or decreased partial pressure of oxygen in blood, Fever greater than 38ºC oral or body temperature lower than that required for normal body function(\< 35ºC), White blood cell count greater than or less than the normal, Greater than 15% immature neutrophils (bands) irrespective of white blood cell count, AND Moderate lung infection * The subject must require initial hospitalization, or treatment in an emergency room or urgent care setting, by the standard of care * The subject's infection would require initial treatment with intravenous antimicrobials * Female subjects of child-bearing potential, and those who are fewer than 2 years post-menopausal, must agree to, and comply with, using highly effective methods of birth control while participating in this study
Exclusion criteria
* Lung Infection of Individual not Recently Hospitalized suitable for outpatient therapy with an oral antimicrobial agent * Confirmed or suspected respiratory tract infections attributable to sources other than bacteria from the individuals not recently hospitalized(e.g., ventilator-associated pneumonia, hospital-acquired pneumonia, visible/gross aspiration pneumonia, suspected viral, fungal, or mycobacterial infection of the lung) * Non-infectious causes of lung lesion (e.g., pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure) * Accumulation of pus in the pleural cavity * Microbiologically-documented infection with a pathogen known to be resistant to ceftriaxone, or epidemiological or clinical context suggesting high likelihood of a ceftriaxone-resistant typical bacterial pathogen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test of Cure (TOC) in CE Population | 7-20 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 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response at End of Treatment (EOT) Visit in MITT Population | Last day of study drug administration | — |
| Clinical Response at End of Treatment (EOT) Visit in CE Population | Last day of study drug administration | — |
| Clinical Response at the Test of Cure (TOC) Visit in MITT Population | 7-20 days after last day of study drug administration | — |
| Clinical Response at the Test of Cure (TOC) Visit in mMITT Population | 7-20 days after last day of study drug administration | — |
| Clinical Response at the Test of Cure (TOC) Visit in ME Population | 7-20 days after last day of study drug administration | — |
| Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | 7-20 days after last dose of study drug | — |
| Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | 7-20 days after last dose of study drug | — |
| Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population | 7-20 days after last day of study drug administration | An outcome is considered as favourable if the per-pathogen response for that subject is either Eradication (An adequate source specimen demonstrates absence of the original baseline pathogen) or presumed eradication (An adequate source specimen was not available to culture and the patient was assessed as a clinical cure). Here, an adequate source specimen is defined as any sample that may yield the growth of a CABP pathogen eg, blood, respiratory specimens, or pleural fluid. |
| Per-Patient Microbiological Response at Test of Cure (TOC) Visit in ME Population | 7-20 days after last day of study drug administration | An outcome is considered as favourable if the per-pathogen response for that subject is either Eradication (An adequate source specimen demonstrates absence of the original baseline pathogen) or presumed eradication (An adequate source specimen was not available to culture and the patient was assessed as a clinical cure). Here, an adequate source specimen is defined as any sample that may yield the growth of a CABP pathogen eg, blood, respiratory specimens, or pleural fluid. |
| Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population | 7-20 days after last day of study drug administration | — |
| Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in CE Population | 7-20 days after last dose of study drug | — |
| Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population | 21-42 days after last day of study drug administration | — |
| Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population | 21-42 days after last day of study drug administration | — |
| Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population | 21-42 days after last dose of study drug | — |
| Microbiological Re-infection/Recurrence at LFU Visit in ME Population | 21-42 days after last dose of study drug | — |
Countries
China, India, South Korea, Taiwan, Vietnam
Participant flow
Recruitment details
The enrollment period was from 13 December 2011 to 26 April 2013
Pre-assignment details
Enrolled patients (patients who gave informed consent) were screened for up to 24 hours to ensure eligibility before being randomized
Participants by arm
| Arm | Count |
|---|---|
| Ceftaroline 600mg Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h) | 381 |
| Ceftriaxone 2g Ceftriaxone for Injection is supplied as 1 g/vial (2 vials for a 2 grams dose) and a 2 grams dose infused over 30 (±10) minutes q24h (±2h). | 382 |
| Total | 763 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 4 |
| Overall Study | Investigator Decision | 3 | 8 |
| Overall Study | Lack of therapeutic response | 0 | 1 |
| Overall Study | Last follow-up visit not conducted | 2 | 0 |
| Overall Study | Lost to Follow-up | 10 | 20 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Surgery | 1 | 0 |
| Overall Study | Withdrawal by Subject | 27 | 33 |
Baseline characteristics
| Characteristic | Ceftaroline 600mg | Ceftriaxone 2g | Total |
|---|---|---|---|
| Age, Continuous | 66.1 Years STANDARD_DEVIATION 14.7 | 65.8 Years STANDARD_DEVIATION 13.86 | 66.0 Years STANDARD_DEVIATION 14.28 |
| Age, Customized <65 years | 155 Participants | 146 Participants | 301 Participants |
| Age, Customized >=65 years | 226 Participants | 236 Participants | 462 Participants |
| Race/Ethnicity, Customized Asian | 381 Participants | 382 Participants | 763 Participants |
| Sex: Female, Male Female | 116 Participants | 110 Participants | 226 Participants |
| Sex: Female, Male Male | 265 Participants | 272 Participants | 537 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 381 | 13 / 383 |
| serious Total, serious adverse events | 30 / 381 | 29 / 383 |
Outcome results
Primary
Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test of Cure (TOC) in CE 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 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: 7-20 days after last dose of study drug
Population: CE population: All patients in the MITT population who also meet the minimal disease criteria for CABP and for whom sufficient information regarding CABP is available to determine the patient's outcome (ie, the patient does not have an indeterminate outcome).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test of Cure (TOC) in CE Population | Clinical Cure | 217 Participants |
| Ceftaroline 600mg | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test of Cure (TOC) in CE Population | Clinical Failure | 41 Participants |
| Ceftriaxone 2g | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test of Cure (TOC) in CE Population | Clinical Cure | 178 Participants |
| Ceftriaxone 2g | Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test of Cure (TOC) in CE Population | Clinical Failure | 62 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 in adult subjects with CABP.95% CI: [2.8, 17.1]
Secondary
Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population
Time frame: 21-42 days after last day of study drug administration
Population: CE population: All patients in the MITT population who also meet the minimal disease criteria for CABP and for whom sufficient information regarding CABP is available to determine the patient's outcome (ie, the patient does not have an indeterminate outcome). For this measure only patients who were cured at TOC could be assessed for relapse.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population | No Clinical relapse | 6 Participants |
| Ceftaroline 600mg | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population | Clinical relapse | 199 Participants |
| Ceftaroline 600mg | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population | Indeterminate | 12 Participants |
| Ceftriaxone 2g | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population | Clinical relapse | 167 Participants |
| Ceftriaxone 2g | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population | No Clinical relapse | 3 Participants |
| Ceftriaxone 2g | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in CE Population | Indeterminate | 8 Participants |
95% CI: [-2.4, 4.5]
Secondary
Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population
Time frame: 21-42 days after last day of study drug administration
Population: All randomized subjects who were intended to receive study treatment and were of PORT risk class III and IV. For this measure only patients who were cured at TOC could be assessed for relapse.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population | Clinical relapse | 286 Participants |
| Ceftaroline 600mg | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population | No Clinical relapse | 7 Participants |
| Ceftaroline 600mg | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population | Indeterminate | 12 Participants |
| Ceftriaxone 2g | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population | Clinical relapse | 244 Participants |
| Ceftriaxone 2g | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population | No Clinical relapse | 5 Participants |
| Ceftriaxone 2g | Clinical Relapse at the LFU Visit for Clinical Cure Patients at Test of Cure (TOC) Visit in MITT Population | Indeterminate | 7 Participants |
95% CI: [-2.5, 3]
Secondary
Clinical Response at End of Treatment (EOT) Visit in CE Population
Time frame: Last day of study drug administration
Population: CE population: All patients in the MITT population who also meet the minimal disease criteria for CABP and for whom sufficient information regarding CABP is available to determine the patient's outcome (ie, the patient does not have an indeterminate outcome).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Clinical Response at End of Treatment (EOT) Visit in CE Population | Clinical Cure | 222 Participants |
| Ceftaroline 600mg | Clinical Response at End of Treatment (EOT) Visit in CE Population | Clinical Failure | 36 Participants |
| Ceftriaxone 2g | Clinical Response at End of Treatment (EOT) Visit in CE Population | Clinical Cure | 186 Participants |
| Ceftriaxone 2g | Clinical Response at End of Treatment (EOT) Visit in CE Population | Clinical Failure | 54 Participants |
95% CI: [1.8, 15.4]
Secondary
Clinical Response at End of Treatment (EOT) Visit in MITT Population
Time frame: Last day of study drug administration
Population: All randomized subjects who were intended to receive study treatment and were of PORT risk class III and IV.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Clinical Response at End of Treatment (EOT) Visit in MITT Population | Clinical Cure | 321 Participants |
| Ceftaroline 600mg | Clinical Response at End of Treatment (EOT) Visit in MITT Population | Clinical Failure | 45 Participants |
| Ceftaroline 600mg | Clinical Response at End of Treatment (EOT) Visit in MITT Population | Indeterminate | 15 Participants |
| Ceftriaxone 2g | Clinical Response at End of Treatment (EOT) Visit in MITT Population | Clinical Cure | 281 Participants |
| Ceftriaxone 2g | Clinical Response at End of Treatment (EOT) Visit in MITT Population | Clinical Failure | 82 Participants |
| Ceftriaxone 2g | Clinical Response at End of Treatment (EOT) Visit in MITT Population | Indeterminate | 19 Participants |
95% CI: [4.9, 16.4]
Secondary
Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population
Time frame: 7-20 days after last dose of study drug
Population: ME population: includes patients who meet criteria for both the CE and mMITT populations. In fact, there were different pathogens isolated and we decided to focus on the 5 ones that occurred the most. Additionally please be informed that patients number will not match even if we present all 18 pathogens due to polymicrobial infections.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Staphylococcus aureus | 4 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Staphylococcus aureus | 4 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Staphylococcus aureus | 0 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Streptococcus pneumoniae | 22 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Streptococcus pneumoniae | 19 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Streptococcus pneumoniae | 3 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Escherichia coli | 3 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Escherichia coli | 3 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Escherichia coli | 0 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Haemophilus influenzae | 12 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Haemophilus influenzae | 11 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Haemophilus influenzae | 1 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Klebsiella pneumoniae | 14 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Klebsiella pneumoniae | 11 Participants |
| Ceftaroline 600mg | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Klebsiella pneumoniae | 3 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Klebsiella pneumoniae | 4 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Staphylococcus aureus | 4 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Escherichia coli | 5 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Staphylococcus aureus | 2 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Haemophilus influenzae | 1 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Staphylococcus aureus | 2 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Escherichia coli | 1 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Haemophilus influenzae | 6 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Streptococcus pneumoniae | 15 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Klebsiella pneumoniae | 12 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Cure - Streptococcus pneumoniae | 13 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Haemophilus influenzae | 7 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Clinical Failure - Streptococcus pneumoniae | 2 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Klebsiella pneumoniae | 16 Participants |
| Ceftriaxone 2g | Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Escherichia coli | 6 Participants |
Secondary
Clinical Response at the Test of Cure (TOC) Visit in ME Population
Time frame: 7-20 days after last day of study drug administration
Population: ME population: The ME population includes patients who meet criteria for both the CE and mMITT populations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Clinical Response at the Test of Cure (TOC) Visit in ME Population | Clinical Cure | 50 Participants |
| Ceftaroline 600mg | Clinical Response at the Test of Cure (TOC) Visit in ME Population | Clinical Failure | 7 Participants |
| Ceftriaxone 2g | Clinical Response at the Test of Cure (TOC) Visit in ME Population | Clinical Cure | 47 Participants |
| Ceftriaxone 2g | Clinical Response at the Test of Cure (TOC) Visit in ME Population | Clinical Failure | 15 Participants |
95% CI: [-2.2, 25.8]
Secondary
Clinical Response at the Test of Cure (TOC) Visit in MITT Population
Time frame: 7-20 days after last day of study drug administration
Population: All randomized subjects who were intended to receive study treatment and were of PORT risk class III and IV.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Clinical Response at the Test of Cure (TOC) Visit in MITT Population | Clinical Cure | 305 Participants |
| Ceftaroline 600mg | Clinical Response at the Test of Cure (TOC) Visit in MITT Population | Clinical Failure | 53 Participants |
| Ceftaroline 600mg | Clinical Response at the Test of Cure (TOC) Visit in MITT Population | Indeterminate | 23 Participants |
| Ceftriaxone 2g | Clinical Response at the Test of Cure (TOC) Visit in MITT Population | Clinical Cure | 256 Participants |
| Ceftriaxone 2g | Clinical Response at the Test of Cure (TOC) Visit in MITT Population | Clinical Failure | 91 Participants |
| Ceftriaxone 2g | Clinical Response at the Test of Cure (TOC) Visit in MITT Population | Indeterminate | 35 Participants |
95% CI: [6.8, 19.2]
Secondary
Clinical Response at the Test of Cure (TOC) Visit in mMITT Population
Time frame: 7-20 days after last day of study drug administration
Population: mMITT population: All subjects in MITT population who meet the minimal disease criteria for CABP and who have at least one typical bacterial organism consistent with a CABP pathogen identified from an appropriate microbiological specimen (eg, blood, sputum, or pleural fluid).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Clinical Response at the Test of Cure (TOC) Visit in mMITT Population | Clinical Cure | 68 Participants |
| Ceftaroline 600mg | Clinical Response at the Test of Cure (TOC) Visit in mMITT Population | Clinical Failure | 9 Participants |
| Ceftaroline 600mg | Clinical Response at the Test of Cure (TOC) Visit in mMITT Population | Indeterminate | 3 Participants |
| Ceftriaxone 2g | Clinical Response at the Test of Cure (TOC) Visit in mMITT Population | Clinical Cure | 67 Participants |
| Ceftriaxone 2g | Clinical Response at the Test of Cure (TOC) Visit in mMITT Population | Clinical Failure | 21 Participants |
| Ceftriaxone 2g | Clinical Response at the Test of Cure (TOC) Visit in mMITT Population | Indeterminate | 8 Participants |
95% CI: [2.7, 27.1]
Secondary
Microbiological Re-infection/Recurrence at LFU Visit in ME Population
Time frame: 21-42 days after last dose of study drug
Population: ME population: The ME population includes patients who meet criteria for both the CE and mMITT populations
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Microbiological Re-infection/Recurrence at LFU Visit in ME Population | Super-Infection | 0 Participants |
| Ceftaroline 600mg | Microbiological Re-infection/Recurrence at LFU Visit in ME Population | Favourable response at TOC | 50 Participants |
| Ceftaroline 600mg | Microbiological Re-infection/Recurrence at LFU Visit in ME Population | No Re-Infection Or Recurrance | 50 Participants |
| Ceftaroline 600mg | Microbiological Re-infection/Recurrence at LFU Visit in ME Population | Re-Infection Or Recurrance | 0 Participants |
| Ceftriaxone 2g | Microbiological Re-infection/Recurrence at LFU Visit in ME Population | Re-Infection Or Recurrance | 1 Participants |
| Ceftriaxone 2g | Microbiological Re-infection/Recurrence at LFU Visit in ME Population | Super-Infection | 1 Participants |
| Ceftriaxone 2g | Microbiological Re-infection/Recurrence at LFU Visit in ME Population | No Re-Infection Or Recurrance | 46 Participants |
| Ceftriaxone 2g | Microbiological Re-infection/Recurrence at LFU Visit in ME Population | Favourable response at TOC | 47 Participants |
Secondary
Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population
Time frame: 21-42 days after last dose of study drug
Population: mMITT population: All subjects in MITT population who meet the minimal disease criteria for CABP and who have at least one typical bacterial organism consistent with a CABP pathogen identified from an appropriate microbiological specimen (eg, blood, sputum, or pleural fluid).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population | Super-Infection | 0 Participants |
| Ceftaroline 600mg | Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population | Favourable response at TOC | 68 Participants |
| Ceftaroline 600mg | Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population | No Re-Infection Or Recurrance | 68 Participants |
| Ceftaroline 600mg | Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population | Re-Infection Or Recurrance | 0 Participants |
| Ceftriaxone 2g | Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population | Re-Infection Or Recurrance | 1 Participants |
| Ceftriaxone 2g | Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population | Super-Infection | 2 Participants |
| Ceftriaxone 2g | Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population | No Re-Infection Or Recurrance | 66 Participants |
| Ceftriaxone 2g | Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population | Favourable response at TOC | 67 Participants |
Secondary
Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in CE Population
Time frame: 7-20 days after last dose of study drug
Population: CE population: All patients in the MITT population who also meet the minimal disease criteria for CABP and for whom sufficient information regarding CABP is available to determine the patient's outcome (ie, the patient does not have an indeterminate outcome).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in CE Population | Failure | 41 Participants |
| Ceftaroline 600mg | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in CE Population | Success | 217 Participants |
| Ceftriaxone 2g | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in CE Population | Success | 178 Participants |
| Ceftriaxone 2g | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in CE Population | Failure | 62 Participants |
95% CI: [2.8, 17.1]
Secondary
Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population
Time frame: 7-20 days after last day of study drug administration
Population: All randomized subjects who were intended to receive study treatment and were of PORT risk class III and IV.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population | Success | 305 Participants |
| Ceftaroline 600mg | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population | Failure | 53 Participants |
| Ceftaroline 600mg | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population | Indeterminate | 23 Participants |
| Ceftriaxone 2g | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population | Success | 256 Participants |
| Ceftriaxone 2g | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population | Failure | 91 Participants |
| Ceftriaxone 2g | Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in MITT Population | Indeterminate | 35 Participants |
95% CI: [6.8, 19.2]
Secondary
Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population
Time frame: 7-20 days after last dose of study drug
Population: ME population: includes patients who meet criteria for both the CE and mMITT populations. In fact, there were different pathogens isolated and we decided to focus on the 5 ones that occurred the most. Additionally please be informed that patients number will not match even if we present all 18 pathogens due to polymicrobial infections.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Streptococcus pneumoniae | 19 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Escherichia coli | 0 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Staphylococcus aureus | 4 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Haemophilus influenzae | 12 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Streptococcus pneumoniae | 3 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Haemophilus influenzae | 11 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Streptococcus pneumoniae | 22 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Haemophilus influenzae | 1 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Escherichia coli | 3 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Klebsiella pneumoniae | 14 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Staphylococcus aureus | 0 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Klebsiella pneumoniae | 11 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Escherichia coli | 3 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Klebsiella pneumoniae | 3 Participants |
| Ceftaroline 600mg | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Staphylococcus aureus | 4 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Klebsiella pneumoniae | 4 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Staphylococcus aureus | 4 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Staphylococcus aureus | 2 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Staphylococcus aureus | 2 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Streptococcus pneumoniae | 15 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Streptococcus pneumoniae | 13 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Streptococcus pneumoniae | 2 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Escherichia coli | 6 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Escherichia coli | 5 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Escherichia coli | 1 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Haemophilus influenzae | 7 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Haemophilus influenzae | 6 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Unfavourable - Haemophilus influenzae | 1 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Klebsiella pneumoniae | 16 Participants |
| Ceftriaxone 2g | Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population | Favourable - Klebsiella pneumoniae | 12 Participants |
Secondary
Per-Patient Microbiological Response at Test of Cure (TOC) Visit in ME Population
An outcome is considered as favourable if the per-pathogen response for that subject is either Eradication (An adequate source specimen demonstrates absence of the original baseline pathogen) or presumed eradication (An adequate source specimen was not available to culture and the patient was assessed as a clinical cure). Here, an adequate source specimen is defined as any sample that may yield the growth of a CABP pathogen eg, blood, respiratory specimens, or pleural fluid.
Time frame: 7-20 days after last day of study drug administration
Population: ME population: The ME population includes patients who meet criteria for both the CE and mMITT populations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in ME Population | Favourable | 50 Participants |
| Ceftaroline 600mg | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in ME Population | Unfavourable | 7 Participants |
| Ceftriaxone 2g | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in ME Population | Favourable | 47 Participants |
| Ceftriaxone 2g | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in ME Population | Unfavourable | 15 Participants |
95% CI: [-2.2, 25.8]
Secondary
Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population
An outcome is considered as favourable if the per-pathogen response for that subject is either Eradication (An adequate source specimen demonstrates absence of the original baseline pathogen) or presumed eradication (An adequate source specimen was not available to culture and the patient was assessed as a clinical cure). Here, an adequate source specimen is defined as any sample that may yield the growth of a CABP pathogen eg, blood, respiratory specimens, or pleural fluid.
Time frame: 7-20 days after last day of study drug administration
Population: mMITT population: All subjects in MITT population who meet the minimal disease criteria for CABP and who have at least one typical bacterial organism consistent with a CABP pathogen identified from an appropriate microbiological specimen (eg, blood, sputum, or pleural fluid).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ceftaroline 600mg | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population | Favourable | 68 Participants |
| Ceftaroline 600mg | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population | Unfavourable | 9 Participants |
| Ceftaroline 600mg | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population | Indeterminate | 3 Participants |
| Ceftriaxone 2g | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population | Favourable | 67 Participants |
| Ceftriaxone 2g | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population | Unfavourable | 21 Participants |
| Ceftriaxone 2g | Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population | Indeterminate | 8 Participants |
95% CI: [2.7, 27.1]