Clinical trial NCT01375036: Registry to Monitor the Susceptibility to Aztreonam of Pseudomonas Aeruginosa Isolates From Cystic Fibrosis Patients
Official title: A Prospective, 5-year Registry Study to Monitor the Susceptibility to Aztreonam of Pseudomonas Aeruginosa (PA) Isolates From Patients With Cystic Fibrosis in the United States [AIR-CF5]
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Keywords: Cystic fibrosis
PA
Pseudomonas aeruginosa
CF
aztreonam
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2011-06-17
Enrollment: 510
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A representative cross-section of individuals with mild (FEV1 75% to ≤ 90% predicted), moderate (FEV1 40% to 74% predicted), or severe (FEV1 \<40% predicted) lung disease and a history of ≥ 2 lower respiratory tract cultures positive for PA (at any time) will be enrolled. This will include approximately 100 individuals with pre-study exposure to Cayston (defined as having received at least one prior 28-day course of Cayston at any time before enrolling into the study). Enrollment will be monitored and potentially modified to ensure that adequate numbers of participants in each disease severity category are included. At the Investigator's discretion, participants enrolled in this study can be allowed to participate in clinical trials with other investigational therapies as appropriate.

Brief summary: This is a prospective, longitudinal, 5-year study that will enroll participants from the existing Cystic Fibrosis Foundation (CFF) patient registry. Each enrolled participant will provide samples for microbiological evaluation, obtained upon enrollment and then once per year thereafter for 5 years.


Eligibility criteria: Key Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.

* Current participant or willingness to participate in the CFF patient registry database
* ≥ 6 years of age
* Subject has CF as diagnosed by one of the following

  * Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test, or
  * Two well-characterized genetic mutations in the CFTR gene, or
  * Abnormal nasal potential difference (NPD) AND accompanying clinical characteristics consistent with CF. For subjects who lack documentation of either a positive sweat chloride test or an abnormal NPD, and who have only one well-characterized genetic mutation of the CFTR gene, the diagnosis of CF is determined by the Investigator.
* FEV1 ≥ 25% predicted and ≤ 90% predicted.
* ≥ 2 lower respiratory tract cultures positive for PA with results documented in the subject's medical history.
* Subject must be able to provide written informed consent/assent prior to any study related procedure; parent/guardian must be able to give written informed consent as necessary prior to any study related procedure.

Key Exclusion Criteria:

Subjects who meet the following exclusion criterion are not to be enrolled in this study.

• Any serious active medical or psychiatric illness that, in the opinion of the Investigator, would interfere with subject assessment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Proportion of participants whose least susceptible Pseudomonas aeruginosa (PA) isolate has a ≥ 4-fold increase in aztreonam minimum inhibitory concentration over 1 year and is above the parenteral breakpoint (> 8 μg/mL)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Annual mean change and mean change from baseline in FEV1 (liters) and FEV1 % predicted
timeFrame: Baseline to Year 5
measure: Annual number of hospitalizations and the total number of hospitalizations at the end of each year
timeFrame: Up to 5 years
measure: Annual number of days hospitalized and the total number of hospitalization days at the end of each year
timeFrame: Up to 5 years
measure: Annual mean change and mean change from baseline in body mass index (BMI)
timeFrame: Baseline to Year 5
measure: Annual number of Cayston treatment courses per participant and the total number of Cayston treatment courses at the end of each year in participants that used Cayston
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital Research Institute
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Denver
country: United States
facility: The Children's Hospital
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Altamonte
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Children's Hospitals & Clinics of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Las Vegas
country: United States
facility: Children's Lung Specialists
state: Nevada
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinati Children's Hosptial Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: The Children's Medical Center of Dayton
state: Ohio
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Keating CL, Zuckerman JB, Singh PK, McKevitt M, Gurtovaya O, Bresnik M, Marshall BC, Saiman L. Pseudomonas aeruginosa Susceptibility Patterns and Associated Clinical Outcomes in People with Cystic Fibrosis following Approval of Aztreonam Lysine for Inhalation. Antimicrob Agents Chemother. 2021 Feb 17;65(3):e02327-20. doi: 10.1128/AAC.02327-20. Print 2021 Feb 17.