The Use of Inhaled Aztreonam in Children With a Tracheostomy Tube and Pseudomonas (A-PACT)

A-PACT: The Use of Inhaled Aztreonam to Eliminate or Decrease the Bacterial Burden of Pseudomonas Aeruginosa in Children With a Tracheostomy Tube.

This is a prospective, case-control clinical trial using inhaled Aztreonam (AZLI) in pediatric patients with a tracheostomy tube colonized with Pseudomonas aeruginosa. The aim of the study is to see if AZLI being taken in a one month on / one month off cycle over the course of a year can decrease the need for systemic antibiotics and/or hospitalizations.

Study Overview

Status

Terminated

Intervention / Treatment

Detailed Description

Inhalation aztreonam (AZLI) is an aerosolized formulation of the monobactam antibiotic aztreonam with lysine as a synthetic substance in place of arginine. This substitution was made as arginine, which is in the intravenous (IV) formulation of aztreonam, can cause airway inflammation as seen in patients with cystic fibrosis when aerosolized. There have been several published studies on the efficacy and adverse effects of aerosolized aztreonam in CF patients. Two placebo-controlled studies of AZLI revealed a benefit in patients with CF and colonization with PsA. AIR-CF1 revealed that a 28-day course of AZLI given three times daily (TID) resulted in improved respiratory symptoms. They measured this improvement by using a cystic fibrosis questionnaire (CFQ-R), measuring forced expiratory volume in 1 second (FEV 1), and measuring bacterial density in sputum. AIR-CF2 demonstrated that a 28-day course of AZLI followed by a 28-day course of Tobramycin Inhaled Solution (TIS) delayed the time to the need for additional inhaled or systemic anti-pseudomonal antibiotics. They also used the CFQ-R and measured FEV1 and found improvement in both when compared to placebo. In AIR-CF3, an open-label 18-month study was conducted to evaluate the efficacy of AZLI using a month on/month off cycle, and to observe long-term effects of the drug. This protocol found that AZLI did have a long-term suppressive effect on PsA as there was a persistent reduction in Pseudomonas CFUs from baseline each month of the study. As expected, the decreases in bacterial density were consistently occurring during on months; and during off months, the density increased toward baseline. Thrice-daily dosing appeared more efficacious than twice-daily dosing. This was attributed to the mode of action of aztreonam, as bacterial killing is dependent on time above the MIC (minimal inhibitory concentration). Adverse events include: cough, respiratory tract congestion, pharyngolaryngeal pain, nasal congestion, dyspnea, hemoptysis, rhinorrhea, wheezing, chest discomfort, crackles lung, pulmonary function testing decreased, non-cardiac chest pain, sinus congestion, sinus headache, dyspnea exacerbated, exertional dyspnea.

Antibiotics currently on the market as inhaled antibiotics include tobramycin (TOBI), polymyxin E (Colistin), and aztreonam (Cayston). Studies of all of these have shown clinical benefits in those with Cystic Fibrosis. Given these findings, there is a growing interest in the use of inhaled antibiotics in other disease processes in which subjects become colonized with bacteria in the lower respiratory tract.

The investigators propose a two-center, prospective, case control clinical trial on the use of inhaled aztreonam (AZLI) in pediatric patients ages 7-21 years with a tracheostomy who have had one of their previous 3 tracheostomy aspirate cultures positive for PsA. Their past history in the previous year of requirement for systemic antibiotics will be used for each subject as the historical control. A tracheostomy aspirate culture will be collected upon initiation of the study. The investigators will subsequently start the participants on AZLI on a one month on/one month off schedule. Tracheal aspirate cultures will continue to be collected quarterly (every 3 months), and the bacterial density will be used for analysis. Goal is to see if there is a decrease need for systemic antibiotics for PsA infection.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 4

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

    • California
      • Oakland, California, United States, 94609
        • Benioff Children's Hospital Oakland

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

7 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • o Age: 7 - 21 years old

    • Currently has a tracheostomy tube
    • One of previous 3 tracheostomy tube aspirate cultures positive for Pseudomonas aeruginosa
    • Non-smoker
    • Ability of parent to provide informed consent, as evidenced by signing a copy of the consent form approved by the Institutional Review Board of the subject's respective study institution.
    • Written assent for children 7-17 years of age.
    • Informed consent for children ages 18-21, as evidence by signing a copy of the consent form approved by the Institutional Review Board of the subject's respective study institution.

Exclusion Criteria:

  • o History of immunodeficiency

    • History of cystic fibrosis. Primary ciliary dyskinesia, or bronchiectasis
    • History of tuberculosis
    • History of positive culture for Burkholderia cepacia
    • Use of inhaled antibiotics in the last 6 months

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: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
All participants will be receiving the study drug
Inhaled antibiotic with anti-pseudomonal properties

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With a Decreased Need for Systemic Antibiotics While on the Study Drug
Time Frame: 1 year
Number of participants with a reduced number of days of systemic antibiotics needed after participant starts using the study drug. (compare 1 year prior to starting study drug to the 1 year while patient is on the study drug)
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bacterial Density
Time Frame: 1 year
See if bacterial density of Pseudomonas is decreased or eliminated with the study drug (will compare all cultures from the year prior to starting the trial to the year during the trial)
1 year
Tracheostomy Tube Type
Time Frame: 1 year
to see if there is a difference in how effective the study drug is depending on what type of trach tube the subject has. Will assess this by looking at the Pseudomonas bacterial density from the tracheostomy tube cultures from the year prior to starting the study drug and compare to the year while on the study drug.
1 year
Number of Participants With a Decreased Number of Hospital Admissions
Time Frame: 1 year

Number of participants with a reduced number of hospital admissions the year prior to starting the study drug compared to the year while taking the study drug.

Can study drug decrease number of hospital admissions form the year prior to starting the study drug compared to the year while taking the study drug?

1 year
Number of Participants With a Decrease in the Duration of Hospitalizations
Time Frame: 1 year
Can the study drug decrease the duration of hospitalizations from the year prior to starting the study drug compared to the year while taking the study drug?
1 year

Collaborators and Investigators

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

Collaborators

Investigators

  • Principal Investigator: Rachna Wadia, MD, UCSF Benioff Children's Hospital Oakland

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)

July 1, 2017

Primary Completion (Actual)

February 20, 2020

Study Completion (Actual)

February 20, 2020

Study Registration Dates

First Submitted

April 18, 2017

First Submitted That Met QC Criteria

May 16, 2017

First Posted (Actual)

May 17, 2017

Study Record Updates

Last Update Posted (Actual)

July 30, 2021

Last Update Submitted That Met QC Criteria

July 9, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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