A Double-Blind, Placebo-Controlled, Parallel Group Phase 2 Dose-Ranging Study of Nebulized Amikacin Delivered Via the Pulmonary Drug Delivery System (PDDS) in Patients With Ventilator-Associated Pneumonia Due to Gram-Negative Organisms
- Conditions
- Ventilator associated pneumonia (VAP) caused by gram negative organisms.
- Registration Number
- EUCTR2005-000060-16-ES
- Lead Sponsor
- Aerogen, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
Patients who meet all of the following criteria are eligible to participate in the study:
1. Men and women, 18 years of age and older
2. On ventilator for at least 48 hours
3. Clinical diagnosis of VAP and physician decision to institute or change antibiotics
4. CPIS = 6 (see Appendix A for reference)
5. At least one positive risk factor for Gram-negative, multi-drug resistant organisms:
a) ventilated for = 5 days
b) antibiotic use within the past two weeks
c) known history of respiratory colonization or respiratory infection with a multi-drug resistant, Gram-negative pathogen
d) institutional history of VAP due to resistant organisms
6. Mechanical ventilation expected to continue for at least 3 days
7. Presence of Gram-negative organism by Gram stain (tracheal aspirate)
8. Presence of confirmed Gram-negative pathogens from tracheal aspirate*
9. Informed consent
*Patients will be reassessed within 12 hours following the receipt of the tracheal aspirate culture results.
Patients whose tracheal aspirate culture results show either Gram-positive
organisms only or Gram-negative, amikacin-resistant organisms with an MIC >
512 µg/mL, will be discontinued from treatment and followed for safety only.
Quantitative culture results of bronchial secretions collected from the mini-BAL, BAL, or bronchoscopic protected brush specimens are not for the assessment of eligibility; they will be used to stratify patients by the presence or absence of pathogens at a level of = 10^5 cfu/mL.
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
Patients who meet any of the following criteria are not eligible to participate in this study:
1. Severe hypoxemia as defined by PaO2/FiO2 < 100
2. PEEP > 15 cm H2O
3. Creatinine > 2 mg/dL or urine output < 0.5 cc/kg/hr for 2 consecutive hours
4. Known hypersensitivity or other contraindication to aminoglycoside antibiotics
5. Pregnant or nursing
6. Patients who would be expected to remain on the ventilator after clearance of
the pneumonia and/or more than 28 days for reasons other than pneumonia,
for example, patients with severe head trauma, chest wall deformities, or
neuromuscular disease that impairs the ability to ventilate without assistance
7. Patients who have already received amikacin for the current episode of VAP
or for any other condition within the previous 28 days.
8. Patients participating in or who have participated in other investigational trials
within the last 28 days
9. Patients with compromised immune systems or who are immune-suppressed,
e.g., HIV patients, bone marrow transplant patients. HIV-positive patients with
low or no measurable viral titers and CD4, CD8 counts WNL are not excluded.
10. Patients with =Grade III neutropenia (< 103 neutrophils/cc)
11. Patients with cystic fibrosis, lung cancer, lung resection, known bronchial
obstruction, or active tuberculosis
12. Morbid obesity (weight/height > 1 kg/cm)
13. Burns greater than 40% of total body surface area.
14. Patients who are or will have been on antibiotics for VAP for greater than 24 hours at the time of randomization are excluded.
15. Uncontrolled infection other than VAP
16. Patients with any concomitant condition that, in the opinion of the investigator, would preclude evaluation of response or make it unlikely that
the contemplated course of therapy and follow-up could be completed.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To select the dose of aerosolized amikacin, for use in conjunction with standard intravenous antibiotic therapy, to carry forward into planned Phase 3 pivotal trials of patients with VAP. The dose will be based on achieving a Cmax for amikacin in respiratory secretions that is greater than or equal to 25 times the reference MIC for hospital acquired organisms and an AUC(0-24h)/MIC that is greater than or equal to 100 times the reference.;Secondary Objective: To assess the safety and tolerability of repeat doses pf aerosolized amikacin on ventilated patients over the duration of a course of therapy.;Primary end point(s): Proportion of patients in each arm who achieve a Cmax for amikacin in tracheal aspirates that is =25X the reference MIC for hospital-acquired organisms, and an AUC(0-24h)/MIC = 100X on Day 1.
- Secondary Outcome Measures
Name Time Method