Nebulized Aztreonam for Prevention of Gram Negative Ventilator-associated Pneumonia

NCT03749226 | Terminated Phase 2

• 1 other identifier: AZLI-2018-AR
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Ventilator Associated Pneumonia; Prevention; Respiratory Infection Other

Keywords

Nebulized antibiotic; Ventilator associated pneumonia; Ventilated associated tracheobronchitis; Aztreonam lysine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Pharmacokinetic of aztreonam lysine in respiratory samples

  day 0 and day 2

• Pharmacokinetic of aztreonam lysine in respiratory samples

  day 0 and day 2

• Pharmacokinetic of aztreonam lysine in respiratory samples

  day 0 and day 2

• Pharmacokinetic of aztreonam lysine in respiratory samples

  day 0 and day 2

• Pharmacokinetic of aztreonam lysine in respiratory samples

  day 0 and day 2

Study Arms (2)

AZLI group

ACTIVE COMPARATOR

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; Device: Aerogen Solo; Device: CombiHaler

Control group

NO INTERVENTION

Patients assigned to control group will no receive any intervention for heavy Gram negative colonization

Interventions

Aztreonam lysine DRUG

nebulization

AZLI group

Aerogen Solo DEVICE

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.

AZLI group

CombiHaler DEVICE

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.

AZLI group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Patients under mechanical ventilation for more than 5 day.
• Patient with heavy colonization by Gram-negative microorganisms.
• No clinical suspicion of infections-related ventilator-associated complications (IVAC) according CDC criteria (Figure 1).
• 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.
• Informed consent signed

You may not qualify if:

• Suspected of IVAC.
• Patients with known hypersensitivity to Aztreonam.
• Patients who received more than 48 hours of broad spectrum antibiotics.
• Evidence of active mycobacterium infections, chronic pulmonary infection or bronchial obstruction.
• Granulomatous disease, lung cancer or lung transplant.
• Acute respiratory distress syndrome (ARDS)
• Woman who is pregnant or breast-feeding while enrolled in this study.
• 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

Sponsors & Collaborators

• Hospital Universitari Joan XXIII de Tarragona.: lead

Study Sites (1)

Critical Care Department - Hospital Universitario de Tarragona Joan XXIII

Tarragona, 43007, Spain

Location

Related Publications (30)

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• Rodriguez A, Cabrera M, Reyes LF, Bodi 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 Deliv. 2017 Dec;14(12):1447-1453. doi: 10.1080/17425247.2017.1393411. Epub 2017 Oct 23.

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MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: November 21, 2018
• Study Start: March 19, 2019
• Primary Completion: September 4, 2019
• Study Completion: December 31, 2019
• Last Updated: July 1, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)