Clinical trial NCT03749226: Nebulized Aztreonam for Prevention of Gram Negative Ventilator-associated Pneumonia
Official title: Efficacy, Safety and Pharmacokinetics Profile of Nebulized Aztreonam Lysine (AZLI) for Prevention of Gram Negative Pneumonia in Heavily Colonized Mechanically Ventilated Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Ventilator Associated Pneumonia
Prevention
Respiratory Infection Other
Keywords: Nebulized antibiotic
Ventilator associated pneumonia
Ventilated associated tracheobronchitis
Aztreonam lysine
Lead sponsor: Hospital Universitari Joan XXIII de Tarragona.
Sponsor class: OTHER
First posted: 2018-11-21
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Twenty consecutive patients heavily colonized by Gram-negative bacteria will be eligible for this study. Patients will be randomized to receive either AZLI nebulized or nothing via 1:1 randomization at study or control group.

Patients assigned to study group will receive nebulized Aztreonam lysine (AZLI 75 mg-dose) three times /day during 5 days by mean of the ultrasonic nebulizer (Aeroneb solo®) plus Combihaler® spacer adapted of the ventilator. All patients will be on conventional volume-control ventilator setting during the antibiotic therapy. Systemic antibiotics will not be used in any patient. If the attending physician saw the need to administer intravenous antibiotics after the patient has entry in the study, this patients should be removed from the study
Primary purpose: PREVENTION

Brief summary: Aerosol antibiotic administration offers the theoretical advantages of achieving high drug concentration at the infection site and low systemic absorption, thereby avoiding toxicity. Antibiotic aerosolization has good results in patients with cystic fibrosis, but data are scarce for patients under mechanical ventilation.

Prospective, randomized 1:1, open-label study to assess the microbiological cure and pharmacokinetics (PK), safety and efficacy of nebulized Aztreonam lysine (75 mg dose) each 8 hr during 5 days in ventilated patients heavily colonized by Gram-negative bacteria. It is planned to include a total of 20 ventilated patients heavily colonized. Only ten of them (active group) will receive 5 days of treatment with nebulized AZLI.The control group will not receive treatment.

Detailed description: The main objectives of this study is:

To compare the microbiological cure at day 5 of treatment and the incidence of Gram-negative IVAC between 7th and 10th days after last dose in patients heavily colonized by Gram-negative bacteria treated with nebulized AZLI vs. no treatment.

The secundary objective of this study are:

1. Safety and tolerability of AZLI administered during 5 days in adults patients under mechanical ventilation heavily colonized by Gram-negative bacteria
2. The pharmacokinetic profile in endotracheal aspirate (EA) or bronchoalveolar lavage (BAL).
3. The plasma levels of nebulized AZLI in patients under mechanical ventilation heavily colonized by Gram-negative bacteria.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years.
2. Patients under mechanical ventilation for more than 5 day.
3. Patient with heavy colonization by Gram-negative microorganisms.
4. No clinical suspicion of infections-related ventilator-associated complications (IVAC) according CDC criteria (Figure 1).
5. Patients or his/her legal representative with ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments.
6. Informed consent signed

Exclusion Criteria:

1. Suspected of IVAC.
2. Patients with known hypersensitivity to Aztreonam.
3. Patients who received more than 48 hours of broad spectrum antibiotics.
4. Evidence of active mycobacterium infections, chronic pulmonary infection or bronchial obstruction.
5. Granulomatous disease, lung cancer or lung transplant.
6. Acute respiratory distress syndrome (ARDS)
7. Woman who is pregnant or breast-feeding while enrolled in this study.
8. Any medical condition which, in the opinion of the Investigator, places the patient at an unacceptable risk for toxicities if entered into the clinical study

Primary outcomes:
measure: Microbiological cure
timeFrame: 5 days
Secondary outcomes:
measure: Pharmacokinetic of aztreonam lysine in respiratory samples
timeFrame: day 0 and day 2
measure: Pharmacokinetic of aztreonam lysine in respiratory samples
timeFrame: day 0 and day 2
measure: Pharmacokinetic of aztreonam lysine in respiratory samples
timeFrame: day 0 and day 2
measure: Pharmacokinetic of aztreonam lysine in respiratory samples
timeFrame: day 0 and day 2
measure: Pharmacokinetic of aztreonam lysine in respiratory samples
timeFrame: day 0 and day 2
measure: Pharmacokinetic profile of aztreonam lysine in serum samples
timeFrame: day 3
measure: Pharmacokinetic profile of aztreonam lysine in serum samples
timeFrame: day 3
measure: Pharmacokinetic profile of aztreonam lysine in serum samples
timeFrame: day 3
measure: SAEs and AEs assessments
timeFrame: 10 days
Other outcomes:
Locations:
city: Tarragona
country: Spain
facility: Critical Care Department - Hospital Universitario de Tarragona Joan XXIII
Study officials:
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