Trial Outcomes & Findings for Evaluation of Ceftaroline Fosamil Versus a Comparator in Adult Subjects With Community-acquired Bacterial Pneumonia (CABP) With Risk for Methicillin-resistant Staphylococcus Aureus (NCT NCT01645735)
NCT ID: NCT01645735
Last Updated: 2016-02-01
Results Overview
Clinical response was defined as meeting all of the following criteria: * Symptom Improvement - Improvement in at least 2 and no worsening of any of the following symptoms compared to baseline: * Cough * Dyspnea * Sputum production * Chest pain * Clinical Stability (per Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines; Mandell et al, 2007): * Temperature ≤ 37.8°C * Heart rate ≤ 100 beats/min * Respiratory rate ≤ 24 breaths/min * Systolic blood pressure ≥ 90 mmHg * Oxygen saturation ≥ 90% * Confusion/disorientation absent
COMPLETED
PHASE4
49 participants
Study Day 4
2016-02-01
Participant Flow
Participant milestones
| Measure |
Ceftaroline
Ceftaroline fosamil 600 mg IV over 60 minutes q8h; treatment duration 5 to 14 days
|
Ceftriaxone Plus Vancomycin
Ceftriaxone 2 g IV q24 plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations; treatment duration 5 to 14 days
|
|---|---|---|
|
Overall Study
STARTED
|
32
|
17
|
|
Overall Study
COMPLETED
|
28
|
16
|
|
Overall Study
NOT COMPLETED
|
4
|
1
|
Reasons for withdrawal
| Measure |
Ceftaroline
Ceftaroline fosamil 600 mg IV over 60 minutes q8h; treatment duration 5 to 14 days
|
Ceftriaxone Plus Vancomycin
Ceftriaxone 2 g IV q24 plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations; treatment duration 5 to 14 days
|
|---|---|---|
|
Overall Study
Physician Decision
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
1
|
Baseline Characteristics
Evaluation of Ceftaroline Fosamil Versus a Comparator in Adult Subjects With Community-acquired Bacterial Pneumonia (CABP) With Risk for Methicillin-resistant Staphylococcus Aureus
Baseline characteristics by cohort
| Measure |
Ceftaroline
n=32 Participants
Ceftaroline fosamil 600 mg IV over 60 minutes q8h
|
Ceftriaxone Plus Vancomycin
n=17 Participants
Ceftriaxone 2g IV over 30 minutes q24h plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations
|
Total
n=49 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.2 years
STANDARD_DEVIATION 17.09 • n=5 Participants
|
68.1 years
STANDARD_DEVIATION 14.14 • n=7 Participants
|
58.3 years
STANDARD_DEVIATION 17.51 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
31 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Creatinine Clearance
|
92.47 mL/min/1.73 m^2
STANDARD_DEVIATION 52.190 • n=5 Participants
|
66.52 mL/min/1.73 m^2
STANDARD_DEVIATION 24.448 • n=7 Participants
|
83.47 mL/min/1.73 m^2
STANDARD_DEVIATION 45.978 • n=5 Participants
|
|
PORT Score
|
89.8 units on a scale
STANDARD_DEVIATION 33.17 • n=5 Participants
|
118.6 units on a scale
STANDARD_DEVIATION 29.47 • n=7 Participants
|
99.8 units on a scale
STANDARD_DEVIATION 34.53 • n=5 Participants
|
PRIMARY outcome
Timeframe: Study Day 4Population: MITT Population: all randomized subjects who receive any amount of IV study drug and who have a confirmed diagnosis of Community-Acquired Bacterial Pneumonia (CABP) with risk factors for Methicillin-Resistant Staphylococcus aureus (MRSA) (excluding those that have a sole atypical pathogen)
Clinical response was defined as meeting all of the following criteria: * Symptom Improvement - Improvement in at least 2 and no worsening of any of the following symptoms compared to baseline: * Cough * Dyspnea * Sputum production * Chest pain * Clinical Stability (per Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines; Mandell et al, 2007): * Temperature ≤ 37.8°C * Heart rate ≤ 100 beats/min * Respiratory rate ≤ 24 breaths/min * Systolic blood pressure ≥ 90 mmHg * Oxygen saturation ≥ 90% * Confusion/disorientation absent
Outcome measures
| Measure |
Ceftaroline
n=32 Participants
Ceftaroline fosamil 600 mg IV over 60 minutes q8h
|
Ceftriaxone Plus Vancomycin
n=17 Participants
Ceftriaxone 2 g IV q24 plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations
|
|---|---|---|
|
Clinical Response at Study Day 4 in the Modified Intent-to-Treat (MITT) Population
Non-Responder
|
16 participants
|
8 participants
|
|
Clinical Response at Study Day 4 in the Modified Intent-to-Treat (MITT) Population
Responder
|
14 participants
|
8 participants
|
|
Clinical Response at Study Day 4 in the Modified Intent-to-Treat (MITT) Population
Incomplete Data
|
2 participants
|
1 participants
|
PRIMARY outcome
Timeframe: Test of Cure, an average of 3 weeksPopulation: MITT Population: all randomized subjects who receive any amount of IV study drug and who have a confirmed diagnosis of CABP with risk factors for MRSA (excluding those that have a sole atypical pathogen)
An assessment of clinical outcome was made by the Investigator at TOC. The clinical outcome categories were: Cure: Resolution of all acute signs and symptoms of CABP or improvement to such an extent that no further antimicrobial therapy was required Failure: Subjects who meet either of the following criteria: * Incomplete resolution or worsening of CABP signs and symptoms or development of new CABP signs or symptoms requiring alternative nonstudy antimicrobial therapy * Death in which CABP is contributory Indeterminate: Study data are not available for evaluation of efficacy for any reason, including: * Death in which CABP is clearly noncontributory * Lost to follow-up * Extenuating circumstances precluding classification as a cure or failure A favorable clinical outcome at Test-of Cure (TOC) was clinical cure.
Outcome measures
| Measure |
Ceftaroline
n=32 Participants
Ceftaroline fosamil 600 mg IV over 60 minutes q8h
|
Ceftriaxone Plus Vancomycin
n=17 Participants
Ceftriaxone 2 g IV q24 plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations
|
|---|---|---|
|
Clinical Outcome at Test of Cure (TOC) in the MITT Population
Clinical Cure
|
27 participants
|
15 participants
|
|
Clinical Outcome at Test of Cure (TOC) in the MITT Population
Clinical Failure
|
3 participants
|
2 participants
|
|
Clinical Outcome at Test of Cure (TOC) in the MITT Population
Indeterminate
|
2 participants
|
0 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Test of Cure, an average of 3 weeksPopulation: mMITT Population: a subset of the MITT Population, including subjects for whom at least 1 typical bacterial pathogen has been identified from an adequate microbiological specimen at baseline
An overall microbiological outcome was derived based on the subject's baseline pathogen. As no follow-up specimens were collected at the TOC visit for any subjects, all microbiological outcomes were derived based strictly on clinical outcomes, as either presumed eradication (ie, source specimen was not available to culture and the subject was assessed as clinical cure) , presumed persistence (ie, source specimen was not available to culture and the subject was assessed as a clinical failure), or indeterminate (ie, source specimen was not available to culture and the subject's clinical response was assessed as indeterminate).
Outcome measures
| Measure |
Ceftaroline
n=25 Participants
Ceftaroline fosamil 600 mg IV over 60 minutes q8h
|
Ceftriaxone Plus Vancomycin
n=14 Participants
Ceftriaxone 2 g IV q24 plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations
|
|---|---|---|
|
Microbiological Outcomes by Baseline Pathogen at TOC in the Microbiological Modified Intent-to-Treat (mMITT) Population
Presumed eradication
|
23 participants
|
12 participants
|
|
Microbiological Outcomes by Baseline Pathogen at TOC in the Microbiological Modified Intent-to-Treat (mMITT) Population
Presumed persistence
|
0 participants
|
2 participants
|
|
Microbiological Outcomes by Baseline Pathogen at TOC in the Microbiological Modified Intent-to-Treat (mMITT) Population
Indeterminate
|
2 participants
|
0 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline (Day 0) to Day 49Population: Safety Population: all randomized subjects who received any amount of IV study drug
Adverse events (AEs), serious adverse events (SAEs), deaths, discontinuation due to AEs
Outcome measures
| Measure |
Ceftaroline
n=32 Participants
Ceftaroline fosamil 600 mg IV over 60 minutes q8h
|
Ceftriaxone Plus Vancomycin
n=17 Participants
Ceftriaxone 2 g IV q24 plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations
|
|---|---|---|
|
Safety Evaluation
Any TEAE
|
17 participants
|
9 participants
|
|
Safety Evaluation
Any study drug-related TEAEs
|
3 participants
|
2 participants
|
|
Safety Evaluation
Any SAEs
|
3 participants
|
2 participants
|
|
Safety Evaluation
Any study drug-related SAEs
|
0 participants
|
0 participants
|
|
Safety Evaluation
Discontinuation of IV or oral study drug due to AE
|
1 participants
|
1 participants
|
|
Safety Evaluation
Discontinuation of IV study drug only due to AE
|
1 participants
|
1 participants
|
|
Safety Evaluation
Deaths
|
1 participants
|
0 participants
|
Adverse Events
Ceftaroline
Ceftriaxone Plus Vancomycin
Serious adverse events
| Measure |
Ceftaroline
n=32 participants at risk
Ceftaroline fosamil 600 mg IV over 60 minutes q8h
|
Ceftriaxone Plus Vancomycin
n=17 participants at risk
Ceftriaxone 2 g IV over 30 minutes q24h plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/32
|
5.9%
1/17
|
|
Cardiac disorders
Cardiac arrest
|
3.1%
1/32
|
0.00%
0/17
|
|
Cardiac disorders
Myocardial Infarction
|
3.1%
1/32
|
0.00%
0/17
|
|
Infections and infestations
Clostridium difficile colitis
|
3.1%
1/32
|
0.00%
0/17
|
|
Investigations
Computerized tomogram thorax abnormal
|
0.00%
0/32
|
5.9%
1/17
|
|
Renal and urinary disorders
Renal failure
|
3.1%
1/32
|
0.00%
0/17
|
Other adverse events
| Measure |
Ceftaroline
n=32 participants at risk
Ceftaroline fosamil 600 mg IV over 60 minutes q8h
|
Ceftriaxone Plus Vancomycin
n=17 participants at risk
Ceftriaxone 2 g IV over 30 minutes q24h plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
6.2%
2/32
|
5.9%
1/17
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/32
|
5.9%
1/17
|
|
General disorders
Asthenia
|
0.00%
0/32
|
5.9%
1/17
|
|
General disorders
Non-cardiac chest pain
|
3.1%
1/32
|
5.9%
1/17
|
|
General disorders
Edema Peripheral
|
0.00%
0/32
|
5.9%
1/17
|
|
Injury, poisoning and procedural complications
Procedural pain
|
6.2%
2/32
|
0.00%
0/17
|
|
Investigations
Blood pressure increased
|
0.00%
0/32
|
5.9%
1/17
|
|
Investigations
Body temperature increased
|
0.00%
0/32
|
5.9%
1/17
|
|
Investigations
Neutrophil count increased
|
0.00%
0/32
|
5.9%
1/17
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/32
|
5.9%
1/17
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/32
|
5.9%
1/17
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/32
|
17.6%
3/17
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.2%
2/32
|
0.00%
0/17
|
|
Nervous system disorders
Headache
|
9.4%
3/32
|
5.9%
1/17
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/32
|
5.9%
1/17
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/32
|
5.9%
1/17
|
|
Vascular disorders
Hypertension
|
0.00%
0/32
|
11.8%
2/17
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/32
|
5.9%
1/17
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/32
|
5.9%
1/17
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/32
|
11.8%
2/17
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/32
|
5.9%
1/17
|
Additional Information
Medical Monitor
Cerexa, Inc
Results disclosure agreements
- Principal investigator is a sponsor employee The data generated in this clinical study are the exclusive property of the Sponsor and are confidential. The Sponsor will make all reasonable efforts to publish the results of the study in an appropriate peer-reviewed journal. Authorship on the primary publication of the results from this study will be based on contributions to study design, enrollment, data analysis, and interpretation of results. Publication of results by the PI will be subject to mutual agreement between the PI and Sponsor.
- Publication restrictions are in place
Restriction type: OTHER