Nebulized Aztreonam for Prevention of Gram Negative Ventilator-associated Pneumonia (AZLIS)

June 29, 2021 updated by: Alejandro Rodriguez Oviedo , MD, Hospital Universitari Joan XXIII de Tarragona.

Efficacy, Safety and Pharmacokinetics Profile of Nebulized Aztreonam Lysine (AZLI) for Prevention of Gram Negative Pneumonia in Heavily Colonized Mechanically Ventilated Patients

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.

Study Overview

Status

Terminated

Conditions

Intervention / 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 Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Tarragona, Spain, 43007
        • Critical Care Department - Hospital Universitario de Tarragona Joan XXIII

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: AZLI 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
Drug: Aztreonam lysine
nebulization
Device: Aerogen Solo
Aerogen's vibrating mesh technology, available within the Aerogen® Solo has been adopted for use of conventional mechanical ventilation. Aerogen Solo utilizes active vibrating mesh technology, where energy applied to the vibrational element, causes vibration of each of the 1000 funnel shaped apertures within the mesh. The mesh acts as a micropump drawing liquid through the holes producing a low velocity aerosol optimized for targeted drug delivery to the lungs. According our study (Rodriguez A et al , Expert Opin Drug Deliv. 2017 Dec;14(12):1447-1453) Aeroneb Solo showed an excellent aerosol delivery profile for Aztreonam lysine (AZLI) in an in vitro model of MV with short drug delivery time.
Device: CombiHaler
The inhalation chamber CombiHaler™ spacer for mechanical ventilation and critical care (ICU) allows using both a vibrating mesh nebulizer such as Aeroneb ™, and a pMDI. It saves 50% of the nebulized drug when used in invasive ventilation. The inhalation chamber CombiHaler® is integrated on a circuit of a breathing device in invasive ventilation in particular for connexion of an Aeroneb® Pro or an Aeroneb® Solo. According our study (Rodriguez A et al , Expert Opin Drug Deliv. 2017 Dec;14(12):1447-1453) a better aerosol delivery performance (30%) was obtained using the Conbihaler spacer.
No Intervention: Control group
Patients assigned to control group will no receive any intervention for heavy Gram negative colonization

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microbiological cure
Time Frame: 5 days
Microbiological cure was defined as endotracheal aspirate (EA) or BAL cultures with consistently negative results after five day of therapy.
5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic of aztreonam lysine in respiratory samples
Time Frame: day 0 and day 2
Maximum bronchial concentration[Cmax]
day 0 and day 2
Pharmacokinetic of aztreonam lysine in respiratory samples
Time Frame: day 0 and day 2
time to maximum bronchial concentration[Tmax]
day 0 and day 2
Pharmacokinetic of aztreonam lysine in respiratory samples
Time Frame: day 0 and day 2
Maximum bronchial concentration [Cmax] in tracheal aspirate (EA) or bronchoalveolar lavage (BAL) samples
day 0 and day 2
Pharmacokinetic of aztreonam lysine in respiratory samples
Time Frame: day 0 and day 2
Area under the bronchial concentration-time curve [AUC] in tracheal aspirate (EA) or bronchoalveolar lavage (BAL) samples
day 0 and day 2
Pharmacokinetic of aztreonam lysine in respiratory samples
Time Frame: day 0 and day 2
Terminal elimination half-time [t1/2] in tracheal aspirate (EA) or bronchoalveolar lavage (BAL) samples
day 0 and day 2
Pharmacokinetic profile of aztreonam lysine in serum samples
Time Frame: day 3
Time to maximum serum concentration[Tmax] in serum samples
day 3
Pharmacokinetic profile of aztreonam lysine in serum samples
Time Frame: day 3
Area under the serum concentration-time curve [AUC] in serum samples
day 3
Pharmacokinetic profile of aztreonam lysine in serum samples
Time Frame: day 3
Terminal elimination half-time [t1/2] in serum samples
day 3
SAEs and AEs assessments
Time Frame: 10 days
adverse events as assessed by CTCAE v5.0
10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitari Joan XXIII de Tarragona.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 19, 2019

Primary Completion (Actual)

September 4, 2019

Study Completion (Actual)

December 31, 2019

Study Registration Dates

First Submitted

April 20, 2018

First Submitted That Met QC Criteria

November 19, 2018

First Posted (Actual)

November 21, 2018

Study Record Updates

Last Update Posted (Actual)

July 1, 2021

Last Update Submitted That Met QC Criteria

June 29, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AZLI-2018-AR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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