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Comparative Study of Ceftaroline vs. Ceftriaxone in Adult Subjects With Community-Acquired Pneumonia (CAP)

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ClinicalTrials.gov Identifier: NCT00621504
Recruitment Status : Completed
First Posted : February 22, 2008
Results First Posted : November 10, 2010
Last Update Posted : March 14, 2017
Sponsor:
Information provided by (Responsible Party):
Forest Laboratories

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Bacterial Pneumonia
Interventions Drug: Ceftaroline fosamil for Injection
Drug: IV Ceftriaxone
Drug: Placebo
Drug: Clarithromycin
Enrollment 606
Recruitment Details The enrollment period was from 02 January 2008 to 29 December 2008
Pre-assignment Details Patients were screened for up to 24 hours
Arm/Group Title Ceftaroline Fosamil for Injection IV Ceftriaxone
Hide Arm/Group Description Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h) Ceftriaxone was administered as a 1-g IV infusion over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h).
Period Title: Overall Study
Started 299 307
Completed 273 282
Not Completed 26 25
Reason Not Completed
Adverse Event             1             3
At the request of sponsor/investigator             1             0
Withdrew consent             9             6
Lost to Follow-up             8             10
Other             1             0
Death             6             6
Arm/Group Title Ceftaroline Fosamil for Injection IV Ceftriaxone Total
Hide Arm/Group Description Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h) Ceftriaxone was administered as a 1-g IV infusion over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h). Total of all reporting groups
Overall Number of Baseline Participants 299 307 606
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 299 participants 307 participants 606 participants
<65 years 154 157 311
>= 65 years 145 150 295
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 299 participants 307 participants 606 participants
61.0  (16.6) 61.0  (16.6) 61.0  (16.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 299 participants 307 participants 606 participants
Female
108
  36.1%
112
  36.5%
220
  36.3%
Male
191
  63.9%
195
  63.5%
386
  63.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 299 participants 307 participants 606 participants
Hispanic 29 27 56
Non-Hispanic 270 280 550
1.Primary Outcome
Title Clinical Cure Rate at Test-of-Cure (TOC) in the Modified Intent-to-Treat Efficacy (MITTE) Populations
Hide 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 adverse event (AE) leading to discontinuation of study drug therapy, when subject required alternative antimicrobial therapy to treat the pneumonia
  • Death wherein pneumonia (ie,CABP) was considered causative

Indeterminate: Inability to determine an outcome

Time Frame 8 to 15 days after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The MITTE Population consisted of all subjects in the MITT Population (all randomized subjects who received any amount of the study drug) in PORT Risk Class III or IV. The Pneumonia Outcomes Research Team (PORT) scale of CAP severity in which Risk Class I is associated with the lowest risk for mortality and Risk Class V represents the highest risk.
Arm/Group Title Ceftaroline Fosamil for Injection IV Ceftriaxone
Hide Arm/Group Description:
Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h)
Ceftriaxone was administered as a 1-g IV infusion over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h).
Overall Number of Participants Analyzed 291 300
Measure Type: Number
Unit of Measure: participants
Clinical Cure 244 233
Clinical Failure 34 58
Indeterminate 13 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ceftaroline Fosamil for Injection, IV Ceftriaxone
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 and MITTE Populations in adult subjects with CABP.
Type of Statistical Test Non-Inferiority or Equivalence
Comments A two-sided 95% Confidence Interval (CI) for the observed difference in the primary outcome measure (clinical cure rate) between the ceftaroline group and the ceftriaxone group was calculated based on each of the CE and the MITTE Populations at the TOC visit. Noninferiority was concluded if the lower limit of the 95% CI was higher than –10% for each of the CE and MITTE Populations.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.2
Confidence Interval (2-Sided) 95%
-0.2 to 12.6
Estimation Comments Risk difference corresponds to Ceftaroline clinical cure rate minus Ceftriaxone clinical cure rate. The confidence interval was calculated using the Miettinen and Nurminen method without adjustment.
2.Primary Outcome
Title Clinical Cure Rate for Ceftaroline Compared to That for Ceftriaxone at Test-of-Cure (TOC) in the Clinically Evaluable (CE) Population
Hide Description [Not Specified]
Time Frame 8-15 days after last dose of study drug
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Clinical Response at End of Therapy (EOT)
Hide Description [Not Specified]
Time Frame Last day of study drug administration
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Microbiological Success Rate at Test of Cure (TOC)
Hide Description [Not Specified]
Time Frame 8-15 days after last dose of study drug
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Overall (Clinical and Radiographic) Success Rate at Test of Cure (TOC)
Hide Description [Not Specified]
Time Frame 8-15 days after last day of study drug
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Clinical and Microbiological Response by Pathogen at TOC
Hide Description [Not Specified]
Time Frame 8-15 days after last dose of study drug
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Clinical Relapse at Late Follow Up (LFU)
Hide Description [Not Specified]
Time Frame 21-35 days after last dose of study drug
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Microbiological Re-infection/Recurrence at LFU
Hide Description [Not Specified]
Time Frame 21 to 35 days after last dose of study drug
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Evaluate Safety
Hide Description [Not Specified]
Time Frame first dose, throughout the treatment period, and up to the TOC visit
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description Safety analysis was performed on the Safety Population, consisting of any subject who received any amount of actual study drug
 
Arm/Group Title Ceftaroline Fosamil for Injection IV Ceftriaxone
Hide Arm/Group Description Ceftaroline fosamil was administered in two consecutive 300-mg IV infusions over 30 minutes, every 12 hours (q12h) Ceftriaxone was administered as a 1-g IV infusion over 30 minutes followed by IV saline placebo infused over 30 minutes, every 24 hours (q24h).
All-Cause Mortality
Ceftaroline Fosamil for Injection IV Ceftriaxone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Ceftaroline Fosamil for Injection IV Ceftriaxone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/298 (9.40%)      33/308 (10.71%)    
Blood and lymphatic system disorders     
Anemia  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Lymphadenitis  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Cardiac disorders     
Cardiac failure  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Left ventricular failure  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Ventricular tachycardia  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Cardiac failure acute  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Cardiac failure congestive  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Cardio-respiratory arrest  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Cardiomyopathy  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Cardiopulmonary failure  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Myocardial infarction  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Ischemic cardiomyopathy  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Gastrointestinal disorders     
Gastritis  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Gastrointestinal perforation  1  1/298 (0.34%)  1 0/308 (0.00%)  0
General disorders     
Sudden death  1  2/298 (0.67%)  2 0/308 (0.00%)  0
Multiorgan disorder  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Hepatobiliary disorders     
Acute hepatic failure  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Cholecystitis acute  1  0/298 (0.00%)  0 2/308 (0.65%)  2
Hepatic failure  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Immune system disorders     
Hypersensitivity  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Infections and infestations     
Pneumonia  1  2/298 (0.67%)  2 5/308 (1.62%)  5
Bronchitis  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Empyema  1  1/298 (0.34%)  1 2/308 (0.65%)  2
Pyothorax  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Sepsis  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Tuberculosis  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Cellulitis  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Endocarditis  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Gastroenteritis  1  0/298 (0.00%)  0 2/308 (0.65%)  2
Lung abscess  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Pulmonary tuberculosis  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Urosepsis  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Investigations     
Liver function test abnormal  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Metabolism and nutrition disorders     
Diabetes mellitus  1  1/298 (0.34%)  1 1/308 (0.32%)  1
Gout  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Type 1 diabetes mellitus  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Type 2 diabetes mellitus  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Musculoskeletal and connective tissue disorders     
Myopathy  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung adenocarcinoma  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Lung neoplasm  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Metastases to liver  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Pancreatic neoplasm  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Small cell lung cancer, state unspecified  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Lung adenocarcinoma metastatic  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Nervous system disorders     
Thrombotic stroke  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Renal and urinary disorders     
Urinary retention  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  2/298 (0.67%)  2 1/308 (0.32%)  1
Pleural effusion  1  1/298 (0.34%)  1 1/308 (0.32%)  1
Pulmonary embolism  1  1/298 (0.34%)  1 1/308 (0.32%)  1
Asthma  1  0/298 (0.00%)  0 2/308 (0.65%)  2
Chronic obstructive pulmonary disease  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Vascular disorders     
Aortic aneurysm  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Aortic dissection  1  1/298 (0.34%)  1 0/308 (0.00%)  0
Deep vein thrombosis  1  0/298 (0.00%)  0 1/308 (0.32%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Ceftaroline Fosamil for Injection IV Ceftriaxone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   65/298 (21.81%)      53/308 (17.21%)    
Gastrointestinal disorders     
Diarrhea  1  14/298 (4.70%)  14 7/308 (2.27%)  7
Nausea  1  8/298 (2.68%)  8 8/308 (2.60%)  8
Constipation  1  7/298 (2.35%)  7 5/308 (1.62%)  5
Metabolism and nutrition disorders     
Hypokalemia  1  4/298 (1.34%)  4 10/308 (3.25%)  10
Nervous system disorders     
Headache  1  10/298 (3.36%)  10 4/308 (1.30%)  4
Psychiatric disorders     
Insomnia  1  9/298 (3.02%)  9 6/308 (1.95%)  6
Vascular disorders     
Phlebitis  1  7/298 (2.35%)  7 5/308 (1.62%)  5
Hypertension  1  6/298 (2.01%)  6 8/308 (2.60%)  8
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Vice President, Clinical Sciences
Organization: Cerexa, Inc
Phone: (510) 285-9200
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT00621504     History of Changes
Other Study ID Numbers: P903-08
First Submitted: February 11, 2008
First Posted: February 22, 2008
Results First Submitted: October 12, 2010
Results First Posted: November 10, 2010
Last Update Posted: March 14, 2017