To Compare Safety and Efficacy of Doripenem Versus Imipenem-Cilastatin in Patients With Ventilator-Associated Pneumonia

This study has been terminated.
(Observed lower cure rates and higher mortality rates in one of the treatment groups.)
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00589693
First received: December 21, 2007
Last updated: December 24, 2012
Last verified: December 2012
Results First Received: June 13, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Ventilator-Associated Pneumonia
Interventions: Drug: Doripenem
Drug: Imipenem-Cilastatin
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
274 enrolled patients were randomnly assigned to the 127 study centers. 524 patients were to be enrolled, however as the study was terminated early only 274 patients were actually enrolled.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Out of 274 randomized patients, 41 patients were excluded (as their sites were GCP Non-Compliant) and 6 patients were not treated. Treated patients=227 (115 doripenem and 112 imipenem-cilastatin).

Reporting Groups
  Description
Doripenem 1 g 4-hour infusion intravenously every 8 hour for 7 days
Imipenem-cilastatin 1 g 1-hour infusion intravenously every 8 hour for 10 days

Participant Flow:   Overall Study
    Doripenem     Imipenem-cilastatin  
STARTED     115     112  
COMPLETED     71     83  
NOT COMPLETED     44     29  
randomized in error                 12                 6  
Adverse Event                 4                 4  
Death                 26                 16  
Lack of Efficacy                 0                 1  
Lost to Follow-up                 1                 0  
Physician Decision                 0                 1  
Protocol Violation                 1                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Doripenem 1 g 4-hour infusion intravenously every 8 hour for 7 days
Imipenem-cilastatin 1 g 1-hour infusion intravenously every 8 hour for 10 days
Total Total of all reporting groups

Baseline Measures
    Doripenem     Imipenem-cilastatin     Total  
Number of Participants  
[units: participants]
  115     112     227  
Age  
[units: participants]
     
<=18 years     0     1     1  
Between 18 and 65 years     72     72     144  
>=65 years     43     39     82  
Age  
[units: years]
Mean ± Standard Deviation
  57.5  ± 16.53     54.6  ± 18.46     56.1  ± 17.53  
Gender  
[units: participants]
     
Female     43     37     80  
Male     72     75     147  
Region Enroll  
[units: participants]
     
EUROPE     69     71     140  
NORTH AMERICA     16     12     28  
REST OF WORLD     9     6     15  
SOUTH AMERICA     21     23     44  



  Outcome Measures
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1.  Primary:   Clinical Cure Rate at the End-of-treatment (EOT) Visit   [ Time Frame: End-of-treatment (Day 10 or Day 11) ]

2.  Secondary:   Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom a Qualifying P. Aeruginosa Was Isolated at Baseline   [ Time Frame: End-of-treatment (Day 10 or Day 11) ]

3.  Secondary:   Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom at Least 1 of the Gram-negative Qualifying Pneumonia Pathogens (Enterobacteriaceae, P. Aeruginosa, and Acinetobacter Spp) Was Isolated at Baseline   [ Time Frame: End-of-treatment (Day 10 or Day 11) ]

4.  Secondary:   Number of Patients Who Had Emergence of P. Aeruginosa Resistance   [ Time Frame: Up to 6 weeks ]

5.  Secondary:   28-day All-cause Mortality Rate   [ Time Frame: Up to 28 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
41 patients (21 doripenem, 20 imipenem-cilastatin) were enrolled at 5 sites that were found to be Good Clinical Practice non-compliant and were excluded from the primary efficacy and safety analyses.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Sr Director Clinical Development
Organization: Janssen R&D US
phone: 1 510 248-2310


No publications provided


Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00589693     History of Changes
Other Study ID Numbers: CR014038, DORINOS3008, 2007-004646-33
Study First Received: December 21, 2007
Results First Received: June 13, 2012
Last Updated: December 24, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
India: Ministry of Health
Philippines: Bureau of Food and Drugs
Ukraine: State Pharmacological Center - Ministry of Health