Clinical trial NCT03158116: The Use of Inhaled Aztreonam in Children With a Tracheostomy Tube and Pseudomonas
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Tracheostomy Infection
Keywords: tracheostomy tube
Pseudomonas aeruginosa
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2017-05-17
Enrollment: 5
Sex: ALL
Minimum age (years): 7
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: two-center, prospective, case control clinical trial
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With a Decreased Need for Systemic Antibiotics While on the Study Drug
timeFrame: 1 year
Secondary outcomes:
measure: Bacterial Density
timeFrame: 1 year
measure: Tracheostomy Tube Type
timeFrame: 1 year
measure: Number of Participants With a Decreased Number of Hospital Admissions
timeFrame: 1 year
measure: Number of Participants With a Decrease in the Duration of Hospitalizations
timeFrame: 1 year
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Benioff Children's Hospital Oakland
state: California
Study officials:
affiliation: UCSF Benioff Children's Hospital Oakland
name: Rachna Wadia, MD
role: PRINCIPAL_INVESTIGATOR
References: