Summary
This is a study to examine the effect of combining chronic oral azithromycin with inhaled tobramycin in adolescent and adult subjects with cystic fibrosis who are chronically infected with P. aeruginosa.
Conditions
Cystic Fibrosis
Recruitment Status
Completed
Detailed Description
This study is a prospective, randomized, double-blinded, placebo-controlled trial of azithromycin 500mg taken orally thrice weekly vs. placebo in subjects with cystic fibrosis and chronic airway infection with P. aeruginosa who are utilizing chronic inhaled tobramycin therapy. It will include approximately 120 subjects able to complete a primary 6-week study phase. Subjects will be at least 12 years old with a baseline forced expiratory volume at one second (FEV1) between 25-100% predicted. Subjects will continue to use clinically prescribed inhaled tobramycin cycled on/off every 4 weeks. They will be provided over-encapsulated azithromycin 500mg tablets or placebo during the primary study phase. An optional extension phase will be offered to all subjects completing the primary 6-week study. This 8-week extension phase will include an initial 4 weeks without use of inhaled tobramycin or other inhaled antibiotics, followed by a 4-week period with inhaled tobramycin use. All subjects participating in the extension phase of the study will be provided azithromycin 500mg tablets to be taken thrice weekly for the entire 8-week period. This study will investigate how use of chronic oral azithromycin affects some of the previously demonstrated benefits to health when using inhaled tobramycin. The primary measurements will focus on lung function. Additional measurements will focus on disease-related quality of life as reported by subjects in the trial. Exploratory outcomes, including measurements of safety, are also planned.
Eligibility Criteria
Inclusion Criteria:
12 years old or older
documented diagnosis of cystic fibrosis
written informed consent (and assent when applicable)
at least two respiratory cultures growing P. aeruginosa within the last 12 months
FEV1% predicted between 25-100%
use of at least two cycles of inhaled tobramycin within the last 24 weeks
Off TISP and other inhaled anti-pseudomonal antibiotics for at least 2 weeks at Visit 1 and remain off of any inhaled antibiotics for an additional 2 weeks before starting inhaled tobramycin
most recent liver function test results less than 4 times the upper limit of normal, obtained within the last 12 months
prior or current use of azithromycin for at least four consecutive weeks
stable clinical status and therapeutic regimen
Exclusion Criteria:
weight <40 kg
positive pregnancy test, lactating, or unwillingness to practice a pre-defined form of contraception, which includes abstinence
inability to perform reproducible spirometry
inability or unwillingness to cycle off of inhaled tobramycin for one 4-week period and without use of any additional inhaled antibiotics
respiratory culture with Burkholderia cepacia complex species within 24 months or with nontuberculous mycobacteria within 18 months of screening
use of intravenous or oral anti-pseudomonal antibiotics within 4 weeks of screening
use of investigational therapy within 4 weeks of screening
use of systemic corticosteroids equivalent to a daily dose more than 10mg of prednisone
use of nelfinavir, warfarin, haloperidol, or methadone (concern of drug interaction with azithromycin)
initiation of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy within 30 days
ECG abnormality at screening requiring prompt further medical attention, or QTc interval >480 msec for males and >486 msec for females
any other condition that, in the opinion of the site investigator, would compromise the safety of the subject or quality of the data
Intervention
Intervention Type
Intervention Name
Drug
azithromycin
Drug
placebo (for azithromycin)
Drug
inhaled tobramycin
Phase
Phase 4
Gender
All
Min Age
12 Years
Max Age
N/A
Download Date
June 28, 2021
Principal Investigator
David Nichols, MD
Primary Contact Information
For more information on this trial, visit clinicaltrials.gov.
Contact
For more information and to contact the study team: