Nebulized Aztreonam for Prevention of Gram Negative Ventilator-associated Pneumonia

Phase 2

Terminated

• Conditions: Ventilator Associated Pneumonia; Prevention; Respiratory Infection Other
• Interventions: Drug: Aztreonam lysine; Device: Aerogen Solo; Device: CombiHaler

• Registration Number: NCT03749226
• Lead Sponsor: Hospital Universitari Joan XXIII de Tarragona.

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.

Study Timeline

• Study First Submitted: 2018-04-20
• Study First Submitted QC: 2018-11-19
• Study First Posted: 2018-11-21
• Study Start: 2019-03-19
• Primary Completion: 2019-09-04
• Study Completion: 2019-12-31
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-29
• Last Update Posted: 2021-07-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AZLI group	Aerogen Solo	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
AZLI group	CombiHaler	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
AZLI group	Aztreonam lysine	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

Primary Outcome Measures

Name	Time	Method
Microbiological cure	5 days	Microbiological cure was defined as endotracheal aspirate (EA) or BAL cultures with consistently negative results after five day of therapy.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic of aztreonam lysine in respiratory samples	day 0 and day 2	Terminal elimination half-time \[t1/2\] in tracheal aspirate (EA) or bronchoalveolar lavage (BAL) samples
Pharmacokinetic profile of aztreonam lysine in serum samples	day 3	Terminal elimination half-time \[t1/2\] in serum samples
SAEs and AEs assessments	10 days	adverse events as assessed by CTCAE v5.0

Trial Locations

Locations (1)

Critical Care Department - Hospital Universitario de Tarragona Joan XXIII; 🇪🇸 Tarragona, Spain