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

Primary Purpose

Ventilator-Associated Pneumonia

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Doripenem
Imipenem-Cilastatin
Placebo
Sponsored by
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ventilator-Associated Pneumonia focused on measuring Ventilator-Associated Pneumonia, Pneumonia, hospital-acquired, Doripenem, Imipenem-cilastatin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have new or worsening radiographic infiltrates consistent with ventilator-associated pneumonia that was not related to cardiac or other disease processes Have at least 1 of the following: fever (core body temperature greater than 39.0°C); hypothermia (core body temperature of less than 35.0°C); leukocytosis (increased WBC count); and leukopenia (decreased WBC count) Have developed ventilator-associated pneumonia and have been on mechanical ventilation for more than or equal to 48 hours and on mechanical ventilation at the time that study medication is assigned Have been hospitalized or been in a chronic care facility for consecutive 5 days or more within the last 90 days Have a baseline Clinical Pulmonary Infection Score (CPIS) more than or equal to 6 and an Acute Physiology and Chronic Health Evaluation (APACHE) II score more than 8 and less than 35 Exclusion Criteria: Have received antibiotics for this episode of ventilator-associated pneumonia for more than 24 hours before study medication administration Known presence at baseline of only methicillin-resistant Staphylococcus aureus or Stenotrophomonas infection Acute respiratory distress syndrome Has any of the following conditions: chest trauma with severe lung bruising or loss of stability of the thoracic cage following a fracture of the sternum, ribs, or both, increased amounts of fluid in the lung cavities requiring drainage or pus in the cavity Has active seizure disorder within the last 2 years or brain injury such that imipenem cilastatin would not be administered to the patient in usual practice Has lung cancer within the last 2 years, chronic bronchitis with an increase in severity within the last 30 days, chronic enlargement of the bronchi or bronchioles related to inflammatory disease or obstruction, lung abscess(s), anatomical bronchial obstruction, respiratory tuberculosis on treatment, suspected atypical pneumonia, chemical pneumonitis, cystic fibrosis, congestive heart failure, severe burns to greater than 15% of the body, evidence of severe and chronic liver disease

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Doripenem

Imipenem-Cilastatin

Arm Description

Doripenem from Days 1 to 7 and imipenem-cilastatin placebo from Days 1 to 10

Imipenem-Cilastatin Days 1 to 10 and doripenem placebo from Days 1 to 7

Outcomes

Primary Outcome Measures

Clinical Cure Rate at the End-of-treatment (EOT) Visit
The number of patients who achieved clinical cure at the EOT visit on Day 10. The patient's were classified as clinical cure if they had resolution of signs and symptoms and objective findings of pneumonia to such an extent that no further antimicrobial therapy was necessary.

Secondary Outcome Measures

Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom a Qualifying P. Aeruginosa Was Isolated at Baseline
The clinical cure rate at the EOT visit in patients, whose bronchoalveolar lavage (BAL) or mini-BAL culture results yielded qualifying pneumonia pathogen P. aeruginosa at baseline.
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
The clinical cure rate at the EOT visit in patients whose BAL or mini-BAL culture results yielded at least 1 of the following Gram-negative qualifying pneumonia pathogens was isolated at baseline: any Enterobacteriaceae, P. aeruginosa, and Acinetobacter Spp.
Number of Patients Who Had Emergence of P. Aeruginosa Resistance
Number of patients who had P. aeruginosa isolates with a 4 fold or greater increase in minimum inhibitory concentration (MIC) at anytime during the study (after the study medication is received) from baseline
28-day All-cause Mortality Rate
Number of deaths which occured up to 28 days of the study period due to all causes

Full Information

First Posted
December 21, 2007
Last Updated
December 24, 2012
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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1. Study Identification

Unique Protocol Identification Number
NCT00589693
Brief Title
To Compare Safety and Efficacy of Doripenem Versus Imipenem-Cilastatin in Patients With Ventilator-Associated Pneumonia
Official Title
A Prospective, Randomized, Double-Blind, Double-Dummy, Multicenter Study to Assess the Safety and Efficacy of Doripenem Compared With Imipenem-Cilastatin in the Treatment of Subjects With Ventilator-Associated Pneumonia
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Terminated
Why Stopped
Observed lower cure rates and higher mortality rates in one of the treatment groups.
Study Start Date
April 2008 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to show that doripenem is as effective as imipenem-cilastatin in the treatment of patients with ventilator-associated pneumonia.
Detailed Description
This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor patient knows the treatment that the patient receives), active-controlled (agent that is compared with a study medication to test whether the study medication has a real effect in a clinical study), double-dummy (placebo [inactive substance that is compared with a medication to test whether the medication has a real effect in a clinical study] is administered to maintain the blind when the comparator medication cannot be made identical to the study medication), parallel-group (each group of patients will be treated at the same time), multicenter study to assess the effectiveness and safety of 7 day course of doripenem, compared with 10 day course of imipenem-cilastatin in patients with ventilator-associated pneumonia. This study will consists of 3 phases: (1) a pretreatment phase with a maximum of 24 hours for the screening/baseline visit, (2) a double blind, double dummy, treatment phase of 10 days (Day 1 to Day 10) and an end-of-treatment (EOT) assessment within 24 hours after the last dose of study medication therapy administered on Day 10 or at the time of early withdrawal from study medication, and (3) a post treatment (follow-up) phase consisting of an early follow-up (EFU) visit within 7 to 14 days after the last dose of study medication, and last follow-up (LFU) visit within 28 to 35 days after the last dose of study medication for all patients including those who discontinued study medication early. Two hundred and seventy four patients will be randomly assigned to receive either doripenem or imipenem with placebo of the other medication given simultaneously to maintain the blind (eg, 1 group will receive blinded doripenem from Days 1 to 7 and imipenem placebo Days 1 to 10, other group will receive blinded imipenem Days 1 to 10 and doripenem placebo Days 1 to 7). A sample of secretions from the lower respiratory tract will be obtained by bronchoalveolar lavage (BAL) or mini-BAL within 36 hours prior to administration of study medication from the enrolled patients and sent for culture. Patients, whose baseline BAL or mini-BAL culture results will yield at least 1 qualifying pneumonia pathogen will continue to receive study medication therapy and patients, whose baseline BAL or mini-BAL culture results did not yield at least 1 qualifying pneumonia pathogen will be discontinued from study medication therapy but will remain enroll in the study and will be followed for safety. Safety evaluations including adverse events, clinical laboratory evaluations, vital signs and physical examinations will be monitored throughout the study period. The total duration of an individual patient's participation in the study will be approximately 5 to 6 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ventilator-Associated Pneumonia
Keywords
Ventilator-Associated Pneumonia, Pneumonia, hospital-acquired, Doripenem, Imipenem-cilastatin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
274 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Doripenem
Arm Type
Experimental
Arm Description
Doripenem from Days 1 to 7 and imipenem-cilastatin placebo from Days 1 to 10
Arm Title
Imipenem-Cilastatin
Arm Type
Active Comparator
Arm Description
Imipenem-Cilastatin Days 1 to 10 and doripenem placebo from Days 1 to 7
Intervention Type
Drug
Intervention Name(s)
Doripenem
Intervention Description
Type=exact number, number=1, unit=g, form=solution for injection, route=intravenously. 1 gram 4-hour infusion of doripenem will be administered every 8 hours for 7 days.
Intervention Type
Drug
Intervention Name(s)
Imipenem-Cilastatin
Intervention Description
Type=exact number, number=1, unit=g, form=solution for injection, route=intravenously. 1 gram 1-hour infusion of imipenem-cilastatin will be administered every 8 hours for 10 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Form=solution, route=intravenous. Doripenem pacebo will be administered from Days 1 to 7 in imipenem-cilastatin arm and imipenem-cilastatin placebo will be administered in doripenem arm.
Primary Outcome Measure Information:
Title
Clinical Cure Rate at the End-of-treatment (EOT) Visit
Description
The number of patients who achieved clinical cure at the EOT visit on Day 10. The patient's were classified as clinical cure if they had resolution of signs and symptoms and objective findings of pneumonia to such an extent that no further antimicrobial therapy was necessary.
Time Frame
End-of-treatment (Day 10 or Day 11)
Secondary Outcome Measure Information:
Title
Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom a Qualifying P. Aeruginosa Was Isolated at Baseline
Description
The clinical cure rate at the EOT visit in patients, whose bronchoalveolar lavage (BAL) or mini-BAL culture results yielded qualifying pneumonia pathogen P. aeruginosa at baseline.
Time Frame
End-of-treatment (Day 10 or Day 11)
Title
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
Description
The clinical cure rate at the EOT visit in patients whose BAL or mini-BAL culture results yielded at least 1 of the following Gram-negative qualifying pneumonia pathogens was isolated at baseline: any Enterobacteriaceae, P. aeruginosa, and Acinetobacter Spp.
Time Frame
End-of-treatment (Day 10 or Day 11)
Title
Number of Patients Who Had Emergence of P. Aeruginosa Resistance
Description
Number of patients who had P. aeruginosa isolates with a 4 fold or greater increase in minimum inhibitory concentration (MIC) at anytime during the study (after the study medication is received) from baseline
Time Frame
Up to 6 weeks
Title
28-day All-cause Mortality Rate
Description
Number of deaths which occured up to 28 days of the study period due to all causes
Time Frame
Up to 28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have new or worsening radiographic infiltrates consistent with ventilator-associated pneumonia that was not related to cardiac or other disease processes Have at least 1 of the following: fever (core body temperature greater than 39.0°C); hypothermia (core body temperature of less than 35.0°C); leukocytosis (increased WBC count); and leukopenia (decreased WBC count) Have developed ventilator-associated pneumonia and have been on mechanical ventilation for more than or equal to 48 hours and on mechanical ventilation at the time that study medication is assigned Have been hospitalized or been in a chronic care facility for consecutive 5 days or more within the last 90 days Have a baseline Clinical Pulmonary Infection Score (CPIS) more than or equal to 6 and an Acute Physiology and Chronic Health Evaluation (APACHE) II score more than 8 and less than 35 Exclusion Criteria: Have received antibiotics for this episode of ventilator-associated pneumonia for more than 24 hours before study medication administration Known presence at baseline of only methicillin-resistant Staphylococcus aureus or Stenotrophomonas infection Acute respiratory distress syndrome Has any of the following conditions: chest trauma with severe lung bruising or loss of stability of the thoracic cage following a fracture of the sternum, ribs, or both, increased amounts of fluid in the lung cavities requiring drainage or pus in the cavity Has active seizure disorder within the last 2 years or brain injury such that imipenem cilastatin would not be administered to the patient in usual practice Has lung cancer within the last 2 years, chronic bronchitis with an increase in severity within the last 30 days, chronic enlargement of the bronchi or bronchioles related to inflammatory disease or obstruction, lung abscess(s), anatomical bronchial obstruction, respiratory tuberculosis on treatment, suspected atypical pneumonia, chemical pneumonitis, cystic fibrosis, congestive heart failure, severe burns to greater than 15% of the body, evidence of severe and chronic liver disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
Organizational Affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official's Role
Study Director
Facility Information:
City
Jonesboro
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Arkansas
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United States
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Newark
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Delaware
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Washington
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Jacksonville
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Moline
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Hazard
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Biddeford
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Baltimore
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Detroit
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Buffalo
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Oklahoma City
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Milwaukee
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Buenos Aires
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Argentina
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Cordoba
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Argentina
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Entre Rios
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Argentina
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Monte Grande
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Argentina
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Rio Negro
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Argentina
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Rosario
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Argentina
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Adelaide
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Australia
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Box Hill
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Clayton
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Melbourne
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Parkville N/A
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Brussel
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Belgium
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Gent
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Belgium
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Belo Horizonte
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Curitiba
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Fortaleza
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Porto Alegre
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Rio De Janeiro
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Santo Andre
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Sao Jose Do Rio Preto
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Sao Paulo
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Halifax
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Ottawa
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Ontario
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Greenfield Park N/A
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Quebec
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Argenteuil
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France
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Limoges Cedex 1
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France
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Paris Cedex 15
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France
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Pierre - Benite Cedex
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France
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Tours
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France
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Dresden
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Germany
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Halle/Saale
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Germany
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Homburg/Saar
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Lübeck
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Germany
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Mannheim
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Germany
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Ulm
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Germany
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Cuilapa
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Guatemala
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Escuintla Escuintla
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Guatemala
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Guatemala
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Guatemala
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Budapest N/A
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Hungary
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Budapest Na
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Budapest
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Székesfehérvár
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Bangalore
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India
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Coimbatore
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Ludhiana
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New Delhi
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Pune
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India
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Afula
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Israel
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Petah Tikva
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Ramat-Gan
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Israel
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Chihuahua
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Mexico
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Guadalajara
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Mexico
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Monterrey
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San Luis Potosi
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Zapopan
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Manila
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Quezon City
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Lisboa
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Portugal
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Porto
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Portugal
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Brasov
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Romania
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Targu Mures
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Timisoara
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Romania
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Moscow
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Russian Federation
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Saratov
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Russian Federation
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Smolensk
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Russian Federation
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St Petersburg
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Yaroslavl
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Barcelona
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Spain
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L'Hospitalet De Llobregat
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Spain
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Las Palmas De Gran Canaria
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Spain
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Madrid N/A
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Spain
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Madrid
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Spain
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Tarragona
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Spain
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Chiang Mai
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Thailand
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Khon Kaen
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Thailand
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Nakhonratchasima
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Thailand
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Adana
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Turkey
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Ankara
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Istanbul
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Turkey
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Kayseri
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Samsun
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Turkey
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Trabzon
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Turkey
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Kharkov
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Ukraine
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Kiev
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Ukraine
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Odessa
Country
Ukraine

12. IPD Sharing Statement

Citations:
PubMed Identifier
23148736
Citation
Kollef MH, Chastre J, Clavel M, Restrepo MI, Michiels B, Kaniga K, Cirillo I, Kimko H, Redman R. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care. 2012 Nov 13;16(6):R218. doi: 10.1186/cc11862.
Results Reference
derived

Learn more about this trial

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

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