Nebulized Aztreonam for Prevention of Gram Negative Ventilator-associated Pneumonia

Ventilator Associated Pneumonia Clinical Trial

— AZLIS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03749226
• Other study ID #: AZLI-2018-AR
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: March 19, 2019
• Est. completion date: December 31, 2019

Study information

• Verified date: June 2021
• Source: Hospital Universitari Joan XXIII de Tarragona.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: December 31, 2019
• Est. primary completion date: September 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• Prevention
• Respiratory Infection Other
• Respiratory Tract Infections
• Ventilator Associated Pneumonia

Intervention

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.
• 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.

Locations

Country	Name	City	State
Spain	Critical Care Department - Hospital Universitario de Tarragona Joan XXIII	Tarragona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitari Joan XXIII de Tarragona.

Country where clinical trial is conducted

Spain, 

References & Publications (30)

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Rodríguez A, Cabrera M, Reyes LF, Bodí M, Trefler S, Canadell L, Barahona D, Ehrmann S, Martin-Loeches I, Restrepo MI, Vecellio L. In vitro evaluation of aerosol delivery of aztreonam lysine (AZLI): an adult mechanical ventilation model. Expert Opin Drug — View Citation

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbiological cure	Microbiological cure was defined as endotracheal aspirate (EA) or BAL cultures with consistently negative results after five day of therapy.	5 days
Secondary	Pharmacokinetic of aztreonam lysine in respiratory samples	Maximum bronchial concentration[Cmax]	day 0 and day 2
Secondary	Pharmacokinetic of aztreonam lysine in respiratory samples	time to maximum bronchial concentration[Tmax]	day 0 and day 2
Secondary	Pharmacokinetic of aztreonam lysine in respiratory samples	Maximum bronchial concentration [Cmax] in tracheal aspirate (EA) or bronchoalveolar lavage (BAL) samples	day 0 and day 2
Secondary	Pharmacokinetic of aztreonam lysine in respiratory samples	Area under the bronchial concentration-time curve [AUC] in tracheal aspirate (EA) or bronchoalveolar lavage (BAL) samples	day 0 and day 2
Secondary	Pharmacokinetic of aztreonam lysine in respiratory samples	Terminal elimination half-time [t1/2] in tracheal aspirate (EA) or bronchoalveolar lavage (BAL) samples	day 0 and day 2
Secondary	Pharmacokinetic profile of aztreonam lysine in serum samples	Time to maximum serum concentration[Tmax] in serum samples	day 3
Secondary	Pharmacokinetic profile of aztreonam lysine in serum samples	Area under the serum concentration-time curve [AUC] in serum samples	day 3
Secondary	Pharmacokinetic profile of aztreonam lysine in serum samples	Terminal elimination half-time [t1/2] in serum samples	day 3
Secondary	SAEs and AEs assessments	adverse events as assessed by CTCAE v5.0	10 days