A Prospective, Randomized, Double-Blind, Double-Dummy, MulticenterStudy to Assess the Safety and Efficacy of Doripenem Compared WithImipenem in the Treatment of Subjects with Ventilator-Associated Pneumonia
- Conditions
- Ventilator-Associated PneumoniaMedDRA version: 9.1Level: LLTClassification code 10065153Term: <Manually entered code. Term in E.1.1>
- Registration Number
- EUCTR2007-004646-33-FR
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
·Men or women 18 years of age or older
·Have new or progressive radiographic infiltrates consistent with VAP that is not related to cardiac or other disease processes taken within 12 hours before screening. A CT scan may be required to evaluate parenchymal disease if the chest X-ray is not sufficiently interpretable
·Have at least 1 of the following:
–Fever (in the absence of antipyretics): a rectal temperature greater than 39°C OR an increase in core temperature of greater than 1°C
–Hypothermia, defined as a rectal/core body temperature of less than 35°C
–Leukocytosis (WBC count ³10x109/L or ³15% immature neutrophils, regardless of the total peripheral white cell count; or leukopenia with total WBC count less than 4x109/L
·Have developed VAP and have been on mechanical ventilation for ³48 hours and on mechanical ventilation at the time of randomization. They may have been treated for VAP with antibiotics and have clinical deterioration associated with a probable new pathogen if they have been on a ventilator for >72 hours
·Have been hospitalized or been in a chronic care facility for a total of 5 or more days within the last 90 days
·Have a baseline CPIS of > or equal to 6
·Have an APACHE II Score of >8 and <35
·Have microbiologically suitable LRT sample available (BAL/mini BAL) within 12 hours
before screening
·Women must be postmenopausal (for at least 1 year), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent (at the discretion of the investigator), or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], male partner sterilization) before entry and must agree to continue to use the same method of contraception throughout the study; have a negative serum beta-human chorionic gonadotropin (b hCG] or urine pregnancy test at screening (depending on local regulations)
·Willing to adhere to the prohibitions and restrictions specified in this protocol
·Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Consent may be given for unconscious/incapacitated subjects by a legally authorized representative, according to local regulatory and ethical practice using a subject information sheet and informed consent form approved by the responsible Ethics Committee. When a subject is no longer incapacitated, informed consent will be obtained from the subject at that time.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
·Received antibiotics for this episode of VAP for >24 hours before randomization. Subjects will not be excluded if their prior antibiotic therapy has been given for more than 48 hours, are failing therapy by clinical assessments and the antibiotic has not been changed within the 24-hour period before the first dose of i.v. study drug is given.
·Known presence at baseline of only MRSA or Stenotrophomonas infection
·Acute respiratory distress syndrome (ARDS defined by diffuse radiographic infiltrates and PaO2 to fraction of inspired oxygen [FiO2] ratio <200)
·Has any of the following conditions that interfere with the assessment or interpretation of the diagnosis or response to therapy:
–Chest trauma with lung contusion or flail chest. A CT scan may be required to
distinguish pneumonia from severe lung contusion on the chest X-ray
–Pleural effusion(s) requiring drainage or empyema
–Lung cancer-primary or secondary within the last 2 years
–Chronic bronchitis with an exacerbation within the last 30 days
–Bronchiectasis
–Lung abscess(s)
–Anatomical bronchial obstruction
–Respiratory tuberculosis on treatment
–Suspected atypical pneumonia
–Chemical pneumonitis (e.g., aspiration of gastric contents, inhalation injury)
–Cystic fibrosis
–Congestive Heart Failure as noted by the New York Heart Association Classification IV
–Active seizure disorder within the last 2 year or brain injury such that imipenem would not be administered to the subject in usual practice
–Severe burns to greater than 15% of the body
–Pre-morbid evidence of stigmata of severe and chronic liver disease indicating cirrhosis in the opinion of the investigator
·History of severe impairment of renal function (i.e., a calculated creatinine clearance (CLCR) of less than 10 mL/minute) requiring continuous renal replacement therapy (CRRT), peritoneal dialysis, hemodialysis, hemofiltration, or oliguria (less than 20 mL urine output per hour over 24 hours)
·History of immunocompromising illness, acquired immunodeficiency syndrome (AIDS), or human immunodeficiency virus (HIV) with a CD4 count less than 200 cells/mL within the past 6 months, antiretroviral therapy within the last 60 days, organ (including bone marrow) transplant recipients, hematologic malignancy, and use of immunosuppressive therapy within 60 days, or use of high-dose corticosteroids (e.g greater than 40 mg of systemic prednisone or equivalent per day) in the last 2 weeks. History of rapid tapering steroids completed over 2 weeks before enrollment will be allowed.
·History of any rapidly progressing disease or immediately life-threatening illness (including acute hepatic failure and septic shock. Shock is defined as a systolic blood pressure less than 90 mmHg for greater than 2 hours, despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents.)
·History of hypersensitivity reactions to carbapenems, penicillins, other b lactam antibiotics, or b lactamase inhibitors (subjects with a history of mild skin rash, documented not to have been caused by previous b lactam use are permitted to enroll)
·Have previously received doripenem
·Have previously received meropenem or imipenem in the last week
·Have any other known or suspected condition that may jeopardize adherence to protocol requirements or interpretation of adverse events
·Suspicion of pulmonary edema as a cause of the acute illness
·Hematocrit of less than 22% or hemoglobin of less than 7 g/dL
·Neutropenia with abs
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method