Clinical trial NCT00589693: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Ventilator-Associated Pneumonia
Keywords: Ventilator-Associated Pneumonia
Pneumonia, hospital-acquired
Doripenem
Imipenem-cilastatin
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2008-01-10
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clinical Cure Rate at the End-of-treatment (EOT) Visit
timeFrame: End-of-treatment (Day 10 or Day 11)
Secondary outcomes:
measure: Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom a Qualifying P. Aeruginosa Was Isolated at Baseline
timeFrame: End-of-treatment (Day 10 or Day 11)
measure: 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
timeFrame: End-of-treatment (Day 10 or Day 11)
measure: Number of Patients Who Had Emergence of P. Aeruginosa Resistance
timeFrame: Up to 6 weeks
measure: 28-day All-cause Mortality Rate
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Jonesboro
country: United States
state: Arkansas
city: Newark
country: United States
state: Delaware
city: Washington
country: United States
state: District of Columbia
city: Jacksonville
country: United States
state: Florida
city: Moline
country: United States
state: Illinois
city: Hazard
country: United States
state: Kentucky
city: Biddeford
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Butte
country: United States
state: Montana
city: Buffalo
country: United States
state: New York
city: Winston Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Milwaukee
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Entre Rios
country: Argentina
city: Monte Grande
country: Argentina
city: Rio Negro
country: Argentina
city: Rosario
country: Argentina
city: Adelaide
country: Australia
city: Box Hill
country: Australia
city: Clayton
country: Australia
city: Melbourne
country: Australia
city: Parkville N/A
country: Australia
city: Brussel
country: Belgium
city: Gent
country: Belgium
city: Belo Horizonte
country: Brazil
city: Curitiba
country: Brazil
city: Fortaleza
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio De Janeiro
country: Brazil
city: Santo Andre
country: Brazil
city: Sao Jose Do Rio Preto
country: Brazil
city: Sao Paulo
country: Brazil
city: Halifax
country: Canada
state: Nova Scotia
city: Ottawa
country: Canada
state: Ontario
city: Greenfield Park N/A
country: Canada
state: Quebec
city: Argenteuil
country: France
city: Limoges Cedex 1
country: France
city: Paris Cedex 15
country: France
city: Pierre - Benite Cedex
country: France
city: Tours
country: France
city: Dresden
country: Germany
city: Halle/Saale
country: Germany
city: Homburg/Saar
country: Germany
city: Lübeck
country: Germany
city: Mannheim
country: Germany
city: Ulm
country: Germany
city: Cuilapa
country: Guatemala
city: Escuintla Escuintla
country: Guatemala
city: Guatemala
country: Guatemala
city: Budapest N/A
country: Hungary
city: Budapest Na
country: Hungary
city: Budapest
country: Hungary
city: Székesfehérvár
country: Hungary
city: Bangalore
country: India
city: Coimbatore
country: India
city: Ludhiana
country: India
city: New Delhi
country: India
city: Pune
country: India
city: Afula
country: Israel
city: Petah Tikva
country: Israel
city: Ramat-Gan
country: Israel
city: Chihuahua
country: Mexico
city: Guadalajara
country: Mexico
city: Monterrey
country: Mexico
city: San Luis Potosi
country: Mexico
city: Zapopan
country: Mexico
city: Manila
country: Philippines
city: Quezon City
country: Philippines
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Brasov
country: Romania
city: Targu Mures
country: Romania
city: Timisoara
country: Romania
city: Moscow
country: Russian Federation
city: Saratov
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Barcelona
country: Spain
city: L'Hospitalet De Llobregat
country: Spain
city: Las Palmas De Gran Canaria
country: Spain
city: Madrid N/A
country: Spain
city: Madrid
country: Spain
city: Tarragona
country: Spain
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Nakhonratchasima
country: Thailand
city: Adana
country: Turkey
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Kayseri
country: Turkey
city: Samsun
country: Turkey
city: Trabzon
country: Turkey
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Odessa
country: Ukraine
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
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.