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

NCT00589693 | Terminated Phase 3 Results DMC

• 3 other identifiers: CR014038DORINOS30082007-004646-33
• Study Type: interventional
• Target: 274
• Locations: 21 countries
• Sites: 100

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.

Conditions

Ventilator-Associated Pneumonia

Keywords

Ventilator-Associated Pneumonia; Pneumonia, hospital-acquired; Doripenem; Imipenem-cilastatin

Outcome Measures

Primary Outcomes (1)

• 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.

  End-of-treatment (Day 10 or Day 11)

Secondary Outcomes (4)

• Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom a Qualifying P. Aeruginosa Was Isolated at Baseline

  End-of-treatment (Day 10 or Day 11)

• 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

  End-of-treatment (Day 10 or Day 11)

• Number of Patients Who Had Emergence of P. Aeruginosa Resistance

  Up to 6 weeks

• 28-day All-cause Mortality Rate

  Up to 28 days

Study Arms (2)

Doripenem

EXPERIMENTAL

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

Drug: Doripenem; Drug: Placebo

Imipenem-Cilastatin

ACTIVE COMPARATOR

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

Drug: Imipenem-Cilastatin; Drug: Placebo

Interventions

Doripenem DRUG

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.

Doripenem

Imipenem-Cilastatin DRUG

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.

Imipenem-Cilastatin

Placebo DRUG

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.

Doripenem; Imipenem-Cilastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: lead

Study Sites (100)

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Jonesboro, Arkansas, United States

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Newark, Delaware, United States

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Washington D.C., District of Columbia, United States

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Jacksonville, Florida, United States

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Moline, Illinois, United States

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Hazard, Kentucky, United States

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Biddeford, Maine, United States

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Baltimore, Maryland, United States

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Detroit, Michigan, United States

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Butte, Montana, United States

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Buffalo, New York, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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Milwaukee, Wisconsin, United States

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Buenos Aires, Argentina

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Córdoba, Argentina

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Entre Ríos, Argentina

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Monte Grande, Argentina

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Rio Negro, Argentina

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Rosario, Argentina

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Adelaide, Australia

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Box Hill, Australia

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Clayton, Australia

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Melbourne, Australia

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Parkville, Australia

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Brussels, Belgium

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Ghent, Belgium

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Belo Horizonte, Brazil

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Curitiba, Brazil

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Fortaleza, Brazil

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Porto Alegre, Brazil

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Rio de Janeiro, Brazil

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Santo André, Brazil

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São José do Rio Preto, Brazil

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São Paulo, Brazil

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Halifax, Nova Scotia, Canada

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Ottawa, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Argenteuil, France

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Limoges, France

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Paris, France

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Pierre-Bénite, France

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Tours, France

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Dresden, Germany

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Halle, Germany

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Homburg/Saar, Germany

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Lübeck, Germany

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Mannheim, Germany

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Ulm, Germany

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Cuilapa, Guatemala

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Escuintla Escuintla, Guatemala

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Guatemala City, Guatemala

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Budapest, Hungary

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Budapest Na, Hungary

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Székesfehérvár, Hungary

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Bangalore, India

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Coimbatore, India

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Ludhiana, India

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New Delhi, India

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Pune, India

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Afula, Israel

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Petah Tikva, Israel

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Ramat Gan, Israel

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Chihuahua City, Mexico

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Guadalajara, Mexico

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Monterrey, Mexico

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San Luis Potosí City, Mexico

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Zapopan, Mexico

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Manila, Philippines

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Quezon City, Philippines

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Lisbon, Portugal

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Porto, Portugal

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Brasov, Romania

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Târgu Mureş, Romania

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Timișoara, Romania

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Moscow, Russia

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Saint Petersburg, Russia

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Saratov, Russia

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Smolensk, Russia

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Yaroslavl, Russia

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Barcelona, Spain

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L'Hospitalet de Llobregat, Spain

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Las Palmas de Gran Canaria, Spain

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Madrid, Spain

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Tarragona, Spain

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Chiang Mai, Thailand

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Khon Kaen, Thailand

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Nakhonratchasima, Thailand

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Adana, Turkey (Türkiye)

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Ankara, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Kayseri, Turkey (Türkiye)

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Samsun, Turkey (Türkiye)

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Trabzon, Turkey (Türkiye)

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Kharkiv, Ukraine

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Kiev, Ukraine

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Odesa, Ukraine

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Related Publications (1)

• 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.

  PMID: 23148736 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Healthcare-Associated Pneumonia

Interventions

Doripenem; Cilastatin, Imipenem Drug Combination

Condition Hierarchy (Ancestors)

Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imipenem; Thienamycins; Cilastatin; Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

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.

Results Point of Contact

• Title: Sr Director Clinical Development
• Organization: Janssen R&D US

1 510 248-2310

Study Officials

• Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

  Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 10, 2008
• Study Start: April 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: December 28, 2012
• Results First Posted: July 18, 2012

Record last verified: 2012-12

Locations

GU (3); UA (3); TU (6); US (17); BE (2); RU (5); BR (8); DE (6); ME (5); ES (5); IN (5); FR (5); PT (2); AR (6); IL (3); PH (2); CA (3); HU (3); RO (3); AU (5); TH (3)