A Randomized, Open-Label, Multicenter Study to Assess the Safety and Tolerability of Doripenem Compared With Imipenem in the Treatment of Subjects With Complicated Intra-Abdominal Infections or Ventilator-Associated Pneumonia

• Conditions: MedDRA version: 9.1Level: LLTClassification code 10056570Term: Intra-abdominal infection; MedDRA version: 9.1Level: LLTClassification code 10065153Term: Ventilator associated pneumonia; ventilator-associated pneumoniacomplicated intra-abdominal infections

• Registration Number: EUCTR2007-001117-42-DE
• Lead Sponsor: Janssen Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-09-04
• Last Update Posted: 13 May 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

·Men or women 18 years of age or older
·Women must be postmenopausal , surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study; have a negative serum beta-human chorionic gonadotropin or urine pregnancy test at screening (depending on local regulations).
·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 their next of kin, guardian, or legal representative, according to local regulatory and ethical practice using a subject information sheet and informed consent form approved by the responsible Ethics Committee.

Subjects with VAP must also:
·Have been hospitalized (or been in a chronic care facility) for greater than or equal to 5 days.
·Have received mechanical ventilation for greater than or equal to 48 hours
·Have a Clinical Pulmonary Infection Score (CPIS) of greater than or equal to 5
·Have new or progressive radiographic infiltrates (not related to another disease process).
·Have at least one of the following:
–Fever (in the absence of antipyretics), increase in core temperature of greater than 1°C OR an oral temperature greater than 38°C, a tympanic temperature of 38.5°C, a rectal/core temperature greater than 39°C, a temporal temperature greater than 38.5°C
–Hypothermia, defined as a rectal/core body temperature of less than 35°C (axillary temperature measurements are not acceptable)
–Leukocytosis (a total white blood cell [WBC] count greater than or equal to 10 x 109/L or greater than or equal to 15% immature neutrophils [bands], regardless of total peripheral white count; or leukopenia with total WBC less than 4.5 x 109/L)
·Have microbiologic samples (quantitative BAL and tracheal aspirate) suitable for culture
·Have an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 8 to 29, inclusive

Subjects with cIAI must also:
·Have clinical evidence of intra-abdominal infection
–If enrolled preoperatively, must have evidence of a systemic infection, with at least 1 of the following:
·Fever (oral temperature greater than 38°C) or hypothermia (core body temperature less than 35°C)
·Elevated WBC count (greater than 10,500 cells/mm3)
·Decrease in blood pressure relative to baseline of greater than 15 mmHg systolic (however systolic blood pressure should not be less than 90 mmHg and subject should not have required continued pressor support)
·Increased pulse (greater than 100 beats per minute [bpm]) and respiratory rates (greater than 20 bpm)
·Hypoxemia (partial pressure of oxygen [PaO2] less than 60 mmHg or pulse oximetry less than 90% on room air)
–In addition, if preoperative, must have at least one of the following physical signs consistent with IAI:
·Abdominal pain or tenderness
·Localized or diffuse abdominal wall rigidity
·Mass
·Ileus
·Have a requirement for surgical intervention (e.g., laparotomy, laparoscopic surgery, or percutaneous draining of an abscess) within 24 hours of study entry
·Require antibacterial therapy, in addition to surgical intervention
·Have one of the following eligible diagnoses:
–Cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall
–Diverticular disease with perforation or abscess
–Appendic

Exclusion Criteria

•·History of subjects with acute hepatic failure or acute decompensation of chronic hepatic failure
·History of severe impairment of renal function requiring peritoneal dialysis, hemodialysis, hemofiltration, or oliguria
·History of immunocompromising illness, acquired immunodeficiency syndrome, or human immunodeficiency virus with a CD4 count less than 200 cells/mL within the past 6 months, organ (including bone marrow) transplant recipients, hematologic malignancy, and use of immunosuppressive therapy at screening, including use of high-dose corticosteroids (e.g., greater than 40 mg prednisone or equivalent per day for greater than 2 weeks)
·History of any rapidly progressing disease or immediately life-threatening illness (including acute hepatic failure and septic shock. Sustained 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 imipenem or meropenem in the past week
·Have any other known or suspected condition that may jeopardize adherence to protocol requirements
·Active seizure disorder or brain injury such that imipenem would not be administered to the subject in usual practice
·Hematocrit of less than 25% or hemoglobin of less that 8 g/dL
·Neutropenia with absolute neutrophil count of less than 1,000 cell/mm3. Subjects with neutrophil counts as low as 500 cells/mm3 are permitted if the reduction is due to the acute infection process.
·Platelet count of less than 50,000 cells/mm3
·Is unlikely to survive the 6- to 8-week study period
·Current use of probenecid or valproic acid
·Have received an experimental drug or used an experimental medical device within 1 month before the planned start of treatment.
·Is breast-feeding
·
Additional exclusion criteria for subjects with VAP:
·Subjects with either:
–Known bronchial obstruction or a history of postobstructive pneumonia
–Primary lung cancer or another metastatic malignancy to the lungs
–Cystic fibrosis
–Lung abscess
–Empyema
–Acute respiratory distress syndrome (diffuse radiographic infiltrates and PaO2 to fraction of inspired oxygen [FiO2] ratio less than 200)
–Active pulmonary tuberculosis
–Subjects requiring antibiotic cover for aspiration pneumonia, atypical pneumonia (including known Legionella pneumophila), or Pneumocystis jiroveci (carinii) pneumonia, fungal pneumonia, or known or suspected gastric aspiration (i.e., chemical pneumonitis)
·Subjects with prior antibiotic therapy (active against likely causative pathogens of respiratory infection) will be excluded if the prior antibiotic:
–Was started or added for the current infection
AND
–This new antibiotic has been given for more than 24 hours before the first dose of i.v. study drug therapy.
Note that subjects will not be excluded if their prior antibiotic therapy has been given for more than 48 hours and remains unchanged before the first dose of i.v. study therapy.

Additional exclusion criteria for subjects with cIAI:
·Diagnosis of abdominal wall abscess, small bowel obstruction or ischemic bowel disease without perforation, traumati

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified