Registry to Monitor the Susceptibility to Aztreonam of Pseudomonas Aeruginosa Isolates From Cystic Fibrosis Patients (AIR-CF5)

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]

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis

• Study Type: Observational
• Enrollment (Actual): 510

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital Research Institute
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
    • Denver, Colorado, United States, 80045
      • The Children's Hospital
  • Florida
    • Altamonte, Florida, United States, 32701
      • Central Florida Pulmonary Group
    • Orlando, Florida, United States, 32801
      • Nemours Children's Clinic
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals & Clinics of Minnesota
  • Nevada
    • Las Vegas, Nevada, United States, 89107
      • Children's Lung Specialists
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
    • Cincinnati, Ohio, United States, 45229
      • Cincinati Children's Hosptial Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404
      • The Children's Medical Center of Dayton
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University College of Medicine
    • Philadelphia, Pennsylvania, United States, 19134
      • St. Christopher's Hospital for Children
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201
      • Children's Hospital of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	This proportion will be compared annually over 5 years.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Annual mean change and mean change from baseline in FEV1 (liters) and FEV1 % predicted	Baseline to Year 5
Annual number of hospitalizations and the total number of hospitalizations at the end of each year	Up to 5 years
Annual number of days hospitalized and the total number of hospitalization days at the end of each year	Up to 5 years
Annual mean change and mean change from baseline in body mass index (BMI)	Baseline to Year 5
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	Up to 5 years

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Cystic Fibrosis Foundation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: June 15, 2011
• First Submitted That Met QC Criteria: June 16, 2011
• First Posted (Estimate): June 17, 2011

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: January 9, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Cystic fibrosis; Pseudomonas aeruginosa; CF; PA; aztreonam
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Pseudomonas Infections
• Other Study ID Numbers: GX-US-205-0128