- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03158116
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.
Study Overview
Status
Conditions
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
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
California
-
Oakland, California, United States, 94609
- Benioff Children's Hospital Oakland
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
Collaborators
Investigators
- Principal Investigator: Rachna Wadia, MD, UCSF Benioff Children's Hospital Oakland
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB 2016-009
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
Clinical Trials on Tracheostomy Infection
-
Universitatea de Medicina si Farmacie Iuliu HatieganuRecruitingTracheostomy Complication | Tracheostomy Infection | Tracheostomy HemorrhageRomania
-
Assiut UniversityNot yet recruitingTracheostomy Infection
-
Gamze AkayAtaturk UniversityNot yet recruiting
-
University of MilanASST Santi Paolo e Carlo; Dejan Radovanovic; Marina Gatti; Michele Mondoni; Stefano... and other collaboratorsNot yet recruiting
-
Centre Hospitalier Universitaire, AmiensCompletedTracheostomy Hemorrhage | Tracheostomy Complications | Other Tracheostomy ComplicationsFrance
-
Diskapi Yildirim Beyazit Education and Research...CompletedTracheostomy Complication | Percutaneous Tracheostomy | High-frequency Jet VentilationTurkey
-
Aksaray UniversityNot yet recruitingTracheostomy Complication | Percutaneous Tracheostomy | Airway Trauma | Tracheostomy HemorrhageTurkey
-
Johns Hopkins UniversityNot yet recruitingTracheostomyUnited States
-
Capital Medical UniversityCompleted
Clinical Trials on Inhaled Aztreonam
-
Gilead SciencesCovance; ClinPhone, Inc.; Chiltern International Inc.CompletedCystic FibrosisBelgium, France, Germany, Italy, Netherlands, Spain, United States, Ireland, United Kingdom, Portugal, Austria, Denmark, Switzerland
-
Virginia Commonwealth UniversityEastern Virginia Medical SchoolTerminated
-
Gilead SciencesApproved for marketingCystic Fibrosis | Pseudomonas AeruginosaCanada
-
Gilead SciencesSalus Pharma, Inc.CompletedCystic Fibrosis | Pseudomonas Aeruginosa | Lung Infection | CFUnited States
-
Gilead SciencesApproved for marketingCystic Fibrosis | Pseudomonas Aeruginosa Airway InfectionUnited States, Puerto Rico
-
Qianfoshan HospitalRecruitingCarbapenem-Resistant Enterobacteriaceae InfectionChina
-
Melinta Therapeutics, Inc.CompletedSkin and Subcutaneous Tissue Bacterial Infections | Skin Structures and Soft Tissue InfectionsUnited States, Argentina, Brazil, Bulgaria, Chile, Estonia, Georgia, Hungary, Korea, Republic of, Latvia, Mexico, Moldova, Republic of, Peru, Romania, Slovakia, Taiwan
-
University of DundeeGilead SciencesRecruitingBronchiectasis AdultUnited Kingdom
-
PfizerCompletedBacterial Infections | Complicated InfectionUnited Kingdom
-
Gilead SciencesCompletedCystic FibrosisUnited States, France, Spain, Germany, Austria, Belgium, Italy, Netherlands, Poland