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

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ClinicalTrials.gov Identifier: NCT03158116
Recruitment Status : Recruiting
First Posted : May 17, 2017
Last Update Posted : August 3, 2017
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Rachna Wadia, Children's Hospital & Research Center Oakland

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Tracheostomy Infection Drug: Inhaled Aztreonam Phase 4

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  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Intervention Model Description: two-center, prospective, case control clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A-PACT: The Use of Inhaled Aztreonam to Eliminate or Decrease the Bacterial Burden of Pseudomonas Aeruginosa in Children With a Tracheostomy Tube.
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics
Drug Information available for: Aztreonam

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




Primary Outcome Measures :
  1. Need for Systemic Antibiotics [ Time Frame: 1 year ]
    See if the number of days of systemic antibiotics needed decreases 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)


Secondary Outcome Measures :
  1. 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)

  2. 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.

  3. Hospital admissions [ Time Frame: 1 year ]
    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

  4. Hospital duration [ 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



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Ages Eligible for Study:   7 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03158116


Contacts
Contact: Rachna Wadia, MD 510-575-0635 rawadia@mail.cho.org
Contact: Rachna Wadia, MD 844-724-4140

Locations
United States, California
Benioff Children's Hospital Oakland Recruiting
Oakland, California, United States, 94609
Contact: Rachna Wadia, MD       RaWadia@mail.cho.org   
Contact: Laurie Schumacher, Ph.D    510-428-3076    LSchumacher@mail.cho.org   
Sponsors and Collaborators
Children's Hospital & Research Center Oakland
Gilead Sciences

Responsible Party: Rachna Wadia, Clinical Assistant Professor, Pediatric Pulmonary and Principal Investigator, Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier: NCT03158116     History of Changes
Other Study ID Numbers: IRB 2016-009
First Posted: May 17, 2017    Key Record Dates
Last Update Posted: August 3, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Rachna Wadia, Children's Hospital & Research Center Oakland:
tracheostomy tube
Pseudomonas aeruginosa

Additional relevant MeSH terms:
Pseudomonas Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Aztreonam
Anti-Bacterial Agents
Anti-Infective Agents