Gram-negative Pneumonia
Conditions
Interventions
Aerosolized BAY 41-6551/placebo is given via the Pulmonary Drug Delivery System
[PDDS Clinical] to Intubated and Mechanically Ventilated Patients with Gram
Negative Pneumonia as Adjunctive Therapy t
Sponsors
Bayer
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients of age 18 and older, who are hospitalized, have pneumonia suspected or confirmed to be caused by Gram-negative organisms, and who are intubated and mechanically-ventilated will be selected for this study. In all patients where the pathogen is suspected of being Gram-negative, it should be confirmed as soon as culture results are available. Patients with microbiologically-confirmed pneumonia are those who have a Gram-negative organism cultured from an appropriate respiratory tract specimen collected prior to enrollment. The main inclusion criteria are: * Males and non-pregnant, non-lactating females, 18 years of age or older Intubated and mechanically-ventilated Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest radiograph Presence of Gram-negative organism(s) indicated by Gramstain, or culture of pre-therapy respiratory specimen, or suspected Gram-negative pathogen Impaired oxygenation Clinical Pulmonary Infection Score (CPIS) * 6 The presence of a MDR organism in a pre-therapy respiratory specimen OR at least two risk factors for MDR organisms
Exclusion criteria
Exclusion criteria: The main exclusion criteria are: * A history of hypersensitivity to amikacin, or other aminoglycosides, * Has received systemic Gram-negative antibiotic therapy for greater than 48 hours at the time of administration of first dose of study drug. There should be as minimal a time delay as possible between randomization and first dose of study drug but up to 48 hours will be acceptable. Exception: Systemic antibiotic therapy for more than 48 hours for gram-negative infection prior to administration of first dose of study drug is permitted if the infection is caused by pathogens that are resistant to the antimicrobial agent(s) used, or the patient*s pneumonia is worsening. * Has primary lung cancer (including patients with small cell lung carcinoma/non-small cell lung carcinoma and patients with unknown histology) or another malignancy metastatic to the lungs or other known endobronchial obstructions. Exception: Please note that patients with complete resection of non-small cell lung carcinoma are eligible for the study. * Known or suspected active tuberculosis, cystic fibrosis, human immunodeficiency virus (HIV) infection with CD 4 count 200 cell/mm3, or invasive fungal infection of the lung, lung abscess, or empyema * Known or suspected bacteremia secondary to Staphylococcus aureus * Known or suspected neuromuscular disorders such as myasthenia gravis or parkinsonism * Has had a stroke within five days * A positive urine and/or serum beta-human chorionic gonadotropin (*-hCG) pregnancy test * Burns greater than 40% of total body surface area * Patients with a serum creatinine * 2 mg/dL (177 *mol/L) Exception: Patients with a serum creatinine * 2 mg/dL (177 *mol/L) and being treated with continuous renal replacement therapy (continuous veno-venous hemofiltration [CVVH] and continuous veno-venous hemofiltration with dialysis[CVVH-D]) or daily hemodialysis will receive the aerosol study drug treatment (Section 8.4.6.1) * Neutropenia (Screening absolute neutrophil count [ANC] * 103 neutrophils/mm3) * Has been on mechanical ventilation for * 28 days * Is participating in or has participated in other investigational interventional studies within the last 28 days prior to study treatment * The risk of rapidly fatal illness and death within 72 hours, or any concomitant conditions not related to VAP that, in the opinion of the investigator, precludes completion of study evaluations and the course of therapy * Stem cell transplantation * Patients with documented Legionella infection (eg, Legionella pneumonia) * Has an Acute Physiology and Chronic Health Evaluation II (APACHE II) score
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy variables: The primary efficacy variable will be the clinical response at the Test-of-Cure (TOC) visit in the modified Intent-to-Treat (mITT; ie, ITT population plus a pre-therapy culture positive for a Gram negative respiratory tract pathogen and an APACHE II score of * 10) population. The mITT population will be the primary analysis group. Safety variables: All patients who have received at least one dose of the study drug(s) will be evaluated for safety in a descriptive manner. The safety analysis will include tabulation of the type (using Medical Dictionary for Regulatory Activities [MedDRA] glossary) and frequency of all AEs. Drug-related AEs, serious AEs (SAEs), and premature discontinuations due to AEs will also be summarized, as well as AEs by severity, outcome, and action taken. Incidence tables will be presented for all AEs up to seven days after the end of treatment and for SAEs up to Day 28 visit. All laboratory data will be analyzed using descriptive statistics including identification of laboratory data outside normal ranges. Rates of organ failure will also be summarized by patient as well as by specific organ type. Mortality during the treatment period, Day 15 and Day 28 visit will be summarized. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives are to evaluate the efficacy of BAY 41-6551 (versus placebo) as measured by: * The number of days on mechanical ventilation * The number of ICU days at Day 28 * The total number of days of Gram-negative intravenous (IV) antibiotics per patient * CPIS changes through TOC * The clinical relapse rates at Day 28 * The all all-cause mortality rate during therapy, at Day 15, and at Day 28 * The number of hospital days at Day 28 Secondary microbiological objectives will include comparisons (aerosolized BAY 41-6551 versus placebo) of the: * per pathogen microbiological response rates at the TOC visit * per patient microbiological response rate at the TOC visit * microbiological recurrence rates at the TOC and Day 28 visit * emergence of new respiratory pathogens during the treatment period * emergence of resistance among baseline pathogens in those patients with persistent infection or colonization | — |
Countries
Netherlands
Outcome results
None listed