In This SectionTexas Health Research & Education Institute
Disease or Condition
Pulmonary - Pneumonia
A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of BAY 41-6551 as Adjunctive Therapy in Intubated and Mechinically-Ventilated Patients with Gram-Negative Pneumonia
The main objective of this study is to evaluate the efficacy and safety of adjunctive aerosolized BAY 41-6551 (amikacin sulfate solkution for inhilation) versus aerosol placebo in the treatment of intubated and mechanically ventilated adult patients with Gram-negative pneumonia. Adult patients (age >_ 18 years) with confirmend pneumonia caused by Gram-negative organisms will be selected for this study. They will receive a 10-day course of aerosolized BAY 41-6551 versus placebo as adjunctive therapy. In addition, all patients will receive parenteral antibiotics according to the 2005 ATS/IDSA guidelines for the management of their condition. Patients who are extubated before the 10 day course of aerosol therapy will be continued on aerosolized therapy with a handheld adaptor.
Males and non-pregnant, non-lactating females, 18 years of age or older. For females of child-bearing potential, one of the following medically acceptable contraceptive methods must be used:
a) Double-barrier methods of contraception (eg, condoms plus spermicidal foam)
b) Intrauterine contraceptive device
c) Approved pharmaceutical contraceptive product (eg, birht control pills or patches, long-term injectable or implantable hormonal contraceptive).
Intubated and mechanically-ventilated (patients who have had a tracheotomy maay be considered as possible study participants as long as they are being mechanically ventilated).
Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest readigraph and presence of Gram-negetive organism(s) by either Gram-stain or culture of pre-therapy respirator secretions (eg, acceptable tracheal aspirate [TA], broncholaveolar laveage [BAL], mini-BAL, protective specimen brush [PSB]) plus at least two of the following:
a) Fever, defined as an oral temperature of > 38.0C (100.4F) or a tympanic/rectal/core temperature of > 38.5C (101.3F), or hypothermia, defined as a rectal/core body temperature of < 35.0C (95.0F)
b) Leukocyte count >_ 10,000/mm3 or <_ 4,500/mm3, or an immature neutrophil (band) count > 15% regardless of the peripheral leukocyte count
c) New onset of purulent sputum or respiratory secretions, or a change in the character of sputum.
At least two risk factors for multi-drug resistant (MDR) organisms:
a) Antimirobial therapy in the preceding two weeks
b) Current hospitalization >_ 5 days
c) High Frequency (> 10%) of antibiotic resistance in the community or in the specific hospital unit
d) Immunosuppresive disease and/or therapy
e) Presence of the risk factors for HCAP
f) Hospitalization for two days or more in the preceding 90 days
g) Residence in a nursing home or extended care facility
H) Home infusion therapy (including antibiotics)
i) Chronic dialysis within 30 days
j) Home wound care
k) Family member with multidrug-resistant pathogen.
Be willing and able to give written informed consent. If the patient is unable to give written informed consent, the patient's legally authorized representatiave (LAR) may provide written consent as approved by the IRB.
A history of hypersensitivity to amikacin. other aminoglyosides, or components of the amikacyn solution for inhilation.
Has received antibiotic therapy for Gram-negative pneumonia for greater than 24 hours at the time of randomization.
Has primary lung cancer or another malignancy metastatic to the lungs or other know endobronchial obstrusions.
Known or suspected active tuberculosis, cystic fibrosis, human immunodeficiency viris (HIV) infection with CD4 count < 200 cell/mm3 (HIV testing is not required as part of this protocol), or invasive fungal infection of the lung.
Has had a stroke within five days. Additionally, patients with stroke should not be enrolled if at least one or both of the following apply:
a) There is an increased risk of fatal brain edema as indicated by a history of hypertension or heart failure, major early CT hypodensity exceeding 50% of the middle cerebral artery territory, and/or involvement of additional vascular territories.
b) There is indication for deterioration based on comparison of patients's neurological condition within six hours of planned study drug dosing and patient's meurological condition two days before, judget by applying the NIH Stroke Scale.
A positive serum B-hCG pregnancy test.
Burns greater the 40% of total body surfacce area.
Is participating in or has participated in other investigational interventional studies within the previous 28 days.
Presence of any concomitant condition that, in the opinion of the investigator, would preclude completion of study evaluations or make it unlikely that the comtemplated course of therapy and follow-up could be completed (eg, rapidly falal illness with death likely within the next 72 hours).