Clinical trial NCT02677701: Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)
Official title: TEACH Trial: Testing the Effect of Adding CHronic Azithromycin to Inhaled Tobramycin. A Randomized, Placebo-controlled, Double-blinded Trial of Azithromycin 500mg Thrice Weekly in Combination With Inhaled Tobramycin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cystic Fibrosis
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Cystic Fibrosis Foundation
name: CF Therapeutics Development Network Coordinating Center
First posted: 2016-02-09
Enrollment: 119
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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

Primary outcomes:
measure: Relative Change in Lung Function
timeFrame: baseline (week 0) to week 6 (6 week period)
Secondary outcomes:
measure: Relative Change in Lung Function
timeFrame: week 2 to week 6 (4 week period)
measure: Change in Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS)
timeFrame: baseline (week 0) to week 6 (6 week period)
measure: Change in Cystic Fibrosis Questionnaire - Revised Respiratory Symptom Score (CFQ-R RSS)
timeFrame: baseline (week 0) to week 6 (6 week period)
Other outcomes:
measure: Change in Sputum Pseudomonas Aeruginosa Bacterial Density
timeFrame: baseline (week 0) to week 6 (6 week period)
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital and Health Center at the University of California San Diego
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: The Nemours Children's Clinic - Orlando
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic - Pensacola
state: Florida
city: Boise
country: United States
facility: Saint Luke's Cystic Fibrosis Center of Idaho
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Peoria
country: United States
facility: Saint Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Portland
country: United States
facility: Maine Medical Partners Pediatric Specialty Care
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Health Care
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: The Minnesota Cystic Fibrosis Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Children's Hospital of New York
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center Strong Memorial
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: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Hershey
country: United States
facility: Hershey Medical Center Pennsylvania State University
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Cystic Fibrosis Center
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: National Jewish Health
name: David P Nichols, MD
role: PRINCIPAL_INVESTIGATOR
References: