A Study 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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01371838
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 848
• Locations: 43
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 19.7
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Community-Acquired Bacterial Pneumonia; Lung Infection of Individual Not Recently Hospitalized	Drug: Ceftaroline; Drug: Ceftriaxone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 848 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicentre, Randomised, Double-Blind, Comparative Study 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
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ceftaroline	Drug: Ceftaroline; Two consecutive infusions q12h for 5 to 7 days
Active Comparator: Ceftriaxone plus placebo	Drug: Ceftriaxone; One dose infusion followed by IV saline placebo infused q24h for 5 to 7 days plus two consecutive saline placebo infusion q24h.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Clinical Response at End of Treatment (EOT) Visit in MITT Population [Last day of study drug administration]

2. Clinical Response at End of Treatment (EOT) Visit in CE Population [Last day of study drug administration]

3. Clinical Response at the Test of Cure (TOC) Visit in MITT Population [7-20 days after last day of study drug administration]

4. Clinical Response at the Test of Cure (TOC) Visit in mMITT Population [7-20 days after last day of study drug administration]

5. Clinical Response at the Test of Cure (TOC) Visit in ME Population [7-20 days after last day of study drug administration]

6. Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population [7-20 days after last dose of study drug]

7. Per-Pathogen Microbiological Response at Test of Cure (TOC) Visit by Pathogen in ME Population [7-20 days after last dose of study drug]

8. 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.

9. 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.

10. 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]

11. Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC) Visit in CE Population [7-20 days after last dose of study drug]

12. 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]

13. 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]

14. Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population [21-42 days after last dose of study drug]

15. Microbiological Re-infection/Recurrence at LFU Visit in ME Population [21-42 days after last dose of study drug]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 150 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Beijing		China
2	Research Site	Chengdu		China
3	Research Site	Guang Zhou		China
4	Research Site	Haikou		China
5	Research Site	Hangzhou		China
6	Research Site	Hefei		China
7	Research Site	Jiangyin		China
8	Research Site	Nanchang		China
9	Research Site	Shanghai		China
10	Research Site	Shenyang		China
11	Research Site	Shenzhen		China
12	Research Site	Shijiazhuang		China
13	Research Site	Wuxi		China
14	Research Site	Bangalore		India
15	Research Site	Calicut		India
16	Research Site	Goa		India
17	Research Site	Hyderabad		India
18	Research Site	Jaipur		India
19	Research Site	Lucknow		India
20	Research Site	Ludhiana		India
21	Research Site	Mysore		India
22	Research Site	New Delhi		India
23	Research Site	Trivandrum		India
24	Research Site	Varanasi		India
25	Research Site	Vellore		India
26	Research Site	Anyang-si		Korea, Republic of
27	Research Site	Bucheon-si		Korea, Republic of
28	Research Site	Cheonan-si		Korea, Republic of
29	Research Site	Chuncheon-si		Korea, Republic of
30	Research Site	Daegu		Korea, Republic of
31	Research Site	Daejeon		Korea, Republic of
32	Research Site	Incheon		Korea, Republic of
33	Research Site	Seoul		Korea, Republic of
34	Research Site	Suwon-si		Korea, Republic of
35	Research Site	Wonju-si		Korea, Republic of
36	Research Site	Kaohsiung		Taiwan
37	Research Site	Keelung		Taiwan
38	Research Site	Taichung		Taiwan
39	Research Site	Taipei		Taiwan
40	Research Site	Can Tho		Vietnam
41	Research Site	Hanoi		Vietnam
42	Research Site	Ho Chi Minh		Vietnam
43	Research Site	Hochiminh		Vietnam

Sponsors and Collaborators

• Pfizer
• Forest Laboratories

Investigators

• Study Director: David Melnick, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• D3720C00002 CSR Synopsis
• Revised CSP

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01371838
• Other Study ID Numbers: D3720C00002
• First Posted: Jun 13, 2011
• Last Update Posted: Sep 6, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by Pfizer: Community-Acquired Bacterial Pneumonia
• Additional relevant MeSH terms: Pneumonia; Pneumonia, Bacterial; Ceftriaxone; Ceftaroline fosamil

Study Results

Participant Flow

Recruitment Details	The enrollment period was from 13 December 2011 to 26 April 2013
Pre-assignment Detail	Enrolled patients (patients who gave informed consent) were screened for up to 24 hours to ensure eligibility before being randomized

Arm/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Period Title: Overall Study
STARTED	381	383
COMPLETED	332	317
NOT COMPLETED	49	66

Baseline Characteristics

Arm/Group Title	Ceftaroline 600mg	Ceftriaxone 2g	Total
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).	Total of all reporting groups
Overall Participants	381	382	763
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.1 (14.70)	65.8 (13.86)	66.0 (14.28)
Age, Customized (Number) [Number]
<65 years	155 40.7%	146 38.2%	301 39.4%
>=65 years	226 59.3%	236 61.8%	462 60.6%
Sex: Female, Male (Count of Participants)
Female	116 30.4%	110 28.8%	226 29.6%
Male	265 69.6%	272 71.2%	537 70.4%
Race/Ethnicity, Customized (Number) [Number]
Asian	381 100%	382 100%	763 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test of Cure (TOC) in CE Population
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	258	240
Clinical Cure	217 57%	178 46.6%
Clinical Failure	41 10.8%	62 16.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments	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.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A two-sided 95% CI for the observed difference in the primary outcome measure (clinical cure rate) between the ceftaroline group and the ceftriaxone group was calculated in CE Population at the TOC visit. Noninferiority was concluded if the lower limit of the 95% CI was higher than -10% in CE Population. If non-inferioirity was achieved then a test of superioirty was conducted whereby if lower limit of 95% CI for the difference was >0% superioirty was concluded.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	9.9
	Confidence Interval	(2-Sided) 95%; 2.8 to 17.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

2. Secondary Outcome

Title	Clinical Response at End of Treatment (EOT) Visit in MITT Population
Time Frame	Last day of study drug administration

Outcome Measure Data

Analysis Population Description

All randomized subjects who were intended to receive study treatment and were of PORT risk class III and IV.

Arm/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	381	382
Clinical Cure	321 84.3%	281 73.6%
Clinical Failure	45 11.8%	82 21.5%
Indeterminate	15 3.9%	19 5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	10.7
	Confidence Interval	(2-Sided) 95%; 4.9 to 16.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

3. Secondary Outcome

Title	Clinical Response at End of Treatment (EOT) Visit in CE Population
Time Frame	Last day of study drug administration

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	258	240
Clinical Cure	222 58.3%	186 48.7%
Clinical Failure	36 9.4%	54 14.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	8.5
	Confidence Interval	(2-Sided) 95%; 1.8 to 15.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

4. Secondary Outcome

Title	Clinical Response at the Test of Cure (TOC) Visit in MITT Population
Time Frame	7-20 days after last day of study drug administration

Outcome Measure Data

Analysis Population Description

All randomized subjects who were intended to receive study treatment and were of PORT risk class III and IV.

Arm/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	381	382
Clinical Cure	305 80.1%	256 67%
Clinical Failure	53 13.9%	91 23.8%
Indeterminate	23 6%	35 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	13.0
	Confidence Interval	(2-Sided) 95%; 6.8 to 19.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments. If lower limit of 95% CI for the risk difference was >0% superioirty was concluded in this population.

5. Secondary Outcome

Title	Clinical Response at the Test of Cure (TOC) Visit in mMITT Population
Time Frame	7-20 days after last day of study drug administration

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	80	96
Clinical Cure	68 17.8%	67 17.5%
Clinical Failure	9 2.4%	21 5.5%
Indeterminate	3 0.8%	8 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.2
	Confidence Interval	(2-Sided) 95%; 2.7 to 27.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

6. Secondary Outcome

Title	Clinical Response at the Test of Cure (TOC) Visit in ME Population
Time Frame	7-20 days after last day of study drug administration

Outcome Measure Data

Analysis Population Description

ME population: The ME population includes patients who meet criteria for both the CE and mMITT populations.

Arm/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	57	62
Clinical Cure	50 13.1%	47 12.3%
Clinical Failure	7 1.8%	15 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.9
	Confidence Interval	(2-Sided) 95%; -2.2 to 25.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

7. Secondary Outcome

Title	Clinical Response at Test of Cure (TOC) Visit by Pathogen in ME Population
Time Frame	7-20 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	57	62
Staphylococcus aureus	4 1%	4 1%
Clinical Cure - Staphylococcus aureus	4 1%	2 0.5%
Clinical Failure - Staphylococcus aureus	0 0%	2 0.5%
Streptococcus pneumoniae	22 5.8%	15 3.9%
Clinical Cure - Streptococcus pneumoniae	19 5%	13 3.4%
Clinical Failure - Streptococcus pneumoniae	3 0.8%	2 0.5%
Escherichia coli	3 0.8%	6 1.6%
Clinical Cure - Escherichia coli	3 0.8%	5 1.3%
Clinical Failure - Escherichia coli	0 0%	1 0.3%
Haemophilus influenzae	12 3.1%	7 1.8%
Clinical Cure - Haemophilus influenzae	11 2.9%	6 1.6%
Clinical Failure - Haemophilus influenzae	1 0.3%	1 0.3%
Klebsiella pneumoniae	14 3.7%	16 4.2%
Clinical Cure - Klebsiella pneumoniae	11 2.9%	12 3.1%
Clinical Failure - Klebsiella pneumoniae	3 0.8%	4 1%

8. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	57	62
Staphylococcus aureus	4 1%	4 1%
Favourable - Staphylococcus aureus	4 1%	2 0.5%
Unfavourable - Staphylococcus aureus	0 0%	2 0.5%
Streptococcus pneumoniae	22 5.8%	15 3.9%
Favourable - Streptococcus pneumoniae	19 5%	13 3.4%
Unfavourable - Streptococcus pneumoniae	3 0.8%	2 0.5%
Escherichia coli	3 0.8%	6 1.6%
Favourable - Escherichia coli	3 0.8%	5 1.3%
Unfavourable - Escherichia coli	0 0%	1 0.3%
Haemophilus influenzae	12 3.1%	7 1.8%
Favourable - Haemophilus influenzae	11 2.9%	6 1.6%
Unfavourable - Haemophilus influenzae	1 0.3%	1 0.3%
Klebsiella pneumoniae	14 3.7%	16 4.2%
Favourable - Klebsiella pneumoniae	11 2.9%	12 3.1%
Unfavourable - Klebsiella pneumoniae	3 0.8%	4 1%

9. Secondary Outcome

Title	Per-Patient Microbiological Response at Test of Cure (TOC) Visit in mMITT Population
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	80	96
Favourable	68 17.8%	67 17.5%
Unfavourable	9 2.4%	21 5.5%
Indeterminate	3 0.8%	8 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.2
	Confidence Interval	(2-Sided) 95%; 2.7 to 27.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

10. Secondary Outcome

Title	Per-Patient Microbiological Response at Test of Cure (TOC) Visit in ME Population
Description	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

Outcome Measure Data

Analysis Population Description

ME population: The ME population includes patients who meet criteria for both the CE and mMITT populations.

Arm/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	57	62
Favourable	50 13.1%	47 12.3%
Unfavourable	7 1.8%	15 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.9
	Confidence Interval	(2-Sided) 95%; -2.2 to 25.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

11. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

All randomized subjects who were intended to receive study treatment and were of PORT risk class III and IV.

Arm/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	381	382
Success	305 80.1%	256 67%
Failure	53 13.9%	91 23.8%
Indeterminate	23 6%	35 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	13.0
	Confidence Interval	(2-Sided) 95%; 6.8 to 19.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

12. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	258	240
Success	217 57%	178 46.6%
Failure	41 10.8%	62 16.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	9.9
	Confidence Interval	(2-Sided) 95%; 2.8 to 17.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

13. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	305	256
Clinical relapse	286 75.1%	244 63.9%
No Clinical relapse	7 1.8%	5 1.3%
Indeterminate	12 3.1%	7 1.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -2.5 to 3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

14. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	217	178
Clinical relapse	199 52.2%	167 43.7%
No Clinical relapse	6 1.6%	3 0.8%
Indeterminate	12 3.1%	8 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline 600mg, Ceftriaxone 2g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -2.4 to 4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for risk difference was estimated by 95% Miettinen and Nurminen CI without adjustments.

15. Secondary Outcome

Title	Microbiological Re-infection/Recurrence at LFU Visit in mMITT Population
Time Frame	21-42 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

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/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	80	96
Super-Infection	0 0%	2 0.5%
Favourable response at TOC	68 17.8%	67 17.5%
No Re-Infection Or Recurrance	68 17.8%	66 17.3%
Re-Infection Or Recurrance	0 0%	1 0.3%

16. Secondary Outcome

Title	Microbiological Re-infection/Recurrence at LFU Visit in ME Population
Time Frame	21-42 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

ME population: The ME population includes patients who meet criteria for both the CE and mMITT populations

Arm/Group Title	Ceftaroline 600mg	Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)	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).
Measure Participants	57	62
Super-Infection	0 0%	1 0.3%
Favourable response at TOC	50 13.1%	47 12.3%
No Re-Infection Or Recurrance	50 13.1%	46 12%
Re-Infection Or Recurrance	0 0%	1 0.3%

Adverse Events

Time Frame	first dose, throughout the treatment period, and up to the TOC visit
Adverse Event Reporting Description	All adverse events with an onset date between the date of first dose and test of cure (TOC) or 20 days following the EOT in absence of TOC and all serious adverse events with an onset date between the date of first dose and test of cure (TOC) or 30 days following the EOT in absence of TOC.
Arm/Group Title	Ceftaroline 600mg		Ceftriaxone 2g
Arm/Group Description	Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)		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).
All Cause Mortality
	Ceftaroline 600mg		Ceftriaxone 2g
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ceftaroline 600mg		Ceftriaxone 2g
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/381 (7.9%)		29/383 (7.6%)
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	1/381 (0.3%)	1	1/383 (0.3%)	1
CARDIAC ARREST	0/381 (0%)	0	1/383 (0.3%)	1
CARDIAC FAILURE	1/381 (0.3%)	1	0/383 (0%)	0
CARDIAC FAILURE ACUTE	1/381 (0.3%)	1	0/383 (0%)	0
Gastrointestinal disorders
DIARRHOEA	1/381 (0.3%)	1	0/383 (0%)	0
UPPER GASTROINTESTINAL HAEMORRHAGE	1/381 (0.3%)	1	0/383 (0%)	0
General disorders
ASTHENIA	1/381 (0.3%)	1	1/383 (0.3%)	1
NON-CARDIAC CHEST PAIN	1/381 (0.3%)	1	0/383 (0%)	0
PYREXIA	0/381 (0%)	0	1/383 (0.3%)	1
Hepatobiliary disorders
CHOLECYSTITIS CHRONIC	1/381 (0.3%)	1	0/383 (0%)	0
CHOLELITHIASIS	1/381 (0.3%)	1	0/383 (0%)	0
Infections and infestations
ASPERGILLOSIS	0/381 (0%)	0	1/383 (0.3%)	1
BRONCHITIS	0/381 (0%)	0	1/383 (0.3%)	1
LUNG INFECTION	1/381 (0.3%)	1	1/383 (0.3%)	1
PNEUMONIA	0/381 (0%)	0	1/383 (0.3%)	1
PULMONARY TUBERCULOSIS	0/381 (0%)	0	2/383 (0.5%)	2
SEPSIS	0/381 (0%)	0	1/383 (0.3%)	1
TUBERCULOSIS	1/381 (0.3%)	1	0/383 (0%)	0
URINARY TRACT INFECTION	1/381 (0.3%)	1	1/383 (0.3%)	1
Injury, poisoning and procedural complications
COMPRESSION FRACTURE	1/381 (0.3%)	1	0/383 (0%)	0
FEMORAL NECK FRACTURE	0/381 (0%)	0	1/383 (0.3%)	1
THORACIC VERTEBRAL FRACTURE	1/381 (0.3%)	1	0/383 (0%)	0
Investigations
C-REACTIVE PROTEIN INCREASED	1/381 (0.3%)	1	0/383 (0%)	0
HEPATIC ENZYME INCREASED	0/381 (0%)	0	1/383 (0.3%)	1
Metabolism and nutrition disorders
DECREASED APPETITE	1/381 (0.3%)	1	1/383 (0.3%)	1
DIABETES MELLITUS	0/381 (0%)	0	1/383 (0.3%)	1
GOUT	1/381 (0.3%)	1	0/383 (0%)	0
HYPERKALAEMIA	1/381 (0.3%)	1	0/383 (0%)	0
HYPERNATRAEMIA	1/381 (0.3%)	1	0/383 (0%)	0
HYPONATRAEMIA	0/381 (0%)	0	1/383 (0.3%)	1
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN	1/381 (0.3%)	1	0/383 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATIC CANCER	0/381 (0%)	0	1/383 (0.3%)	1
LUNG NEOPLASM MALIGNANT	1/381 (0.3%)	1	3/383 (0.8%)	3
SMALL CELL LUNG CANCER	1/381 (0.3%)	1	0/383 (0%)	0
Nervous system disorders
COMA	0/381 (0%)	0	1/383 (0.3%)	1
DIZZINESS	1/381 (0.3%)	1	0/383 (0%)	0
Renal and urinary disorders
URINARY RETENTION	1/381 (0.3%)	1	0/383 (0%)	0
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME	0/381 (0%)	0	1/383 (0.3%)	1
ACUTE RESPIRATORY FAILURE	1/381 (0.3%)	1	0/383 (0%)	0
ASTHMA	2/381 (0.5%)	2	1/383 (0.3%)	1
BRONCHIECTASIS	1/381 (0.3%)	1	1/383 (0.3%)	1
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	2/381 (0.5%)	2	6/383 (1.6%)	6
PNEUMOTHORAX	2/381 (0.5%)	2	0/383 (0%)	0
PULMONARY EMBOLISM	1/381 (0.3%)	1	0/383 (0%)	0
Vascular disorders
ARTERIOSCLEROSIS	1/381 (0.3%)	1	1/383 (0.3%)	1
HAEMATOMA	0/381 (0%)	0	1/383 (0.3%)	1
HYPERTENSIVE EMERGENCY	1/381 (0.3%)	1	0/383 (0%)	0
SHOCK	0/381 (0%)	0	1/383 (0.3%)	1
SHOCK HAEMORRHAGIC	1/381 (0.3%)	1	0/383 (0%)	0
VENOUS THROMBOSIS LIMB	0/381 (0%)	0	1/383 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Ceftaroline 600mg		Ceftriaxone 2g
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/381 (6.3%)		13/383 (3.4%)
Gastrointestinal disorders
DIARRHOEA	24/381 (6.3%)	24	13/383 (3.4%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.