Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)

Cystic Fibrosis Clinical Trial

— TEACH  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02677701
• Other study ID #: TEACH-IP-15
• Secondary ID: 1R01HL124053-01A
• Status: Completed
• Phase: Phase 4
• Start date: October 21, 2016
• Est. completion date: February 13, 2020

Study information

• Verified date: June 2021
• Source: Seattle Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: February 13, 2020
• Est. primary completion date: February 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• azithromycin
500mg tablet over-encapsulated to match placebo
• placebo (for azithromycin)

• inhaled tobramycin
clinically prescribed inhaled tobramycin used by subjects participating in the study

Locations

Country	Name	City	State
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	Saint Luke's Cystic Fibrosis Center of Idaho	Boise	Idaho
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Dayton Children's Hospital	Dayton	Ohio
United States	National Jewish Health	Denver	Colorado
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Hershey Medical Center Pennsylvania State University	Hershey	Pennsylvania
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Mercy Kansas City	Kansas City	Missouri
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	The Minnesota Cystic Fibrosis Center	Minneapolis	Minnesota
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Beth Israel Medical Center	New York	New York
United States	Children's Hospital of New York	New York	New York
United States	The Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Stanford University Medical Center	Palo Alto	California
United States	Nemours Children's Clinic - Pensacola	Pensacola	Florida
United States	Saint Francis Medical Center	Peoria	Illinois
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Maine Medical Partners Pediatric Specialty Care	Portland	Maine
United States	Oregon Health Sciences University	Portland	Oregon
United States	University of Rochester Medical Center Strong Memorial	Rochester	New York
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Intermountain Cystic Fibrosis Center	Salt Lake City	Utah
United States	Rady Children's Hospital and Health Center at the University of California San Diego	San Diego	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	University of Massachusetts Memorial Health Care	Worcester	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Seattle Children's Hospital	CF Therapeutics Development Network Coordinating Center, Cystic Fibrosis Foundation, National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Sputum Pseudomonas Aeruginosa Bacterial Density	Absolute change in log10 transformed quantitative Pseudomonas aeruginosa (Pa) bacterial density as measured by colony forming units (CFUs) per mL of sputum from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Culture results below the lower limit of detection of 1x10^2 were set to 1/2 of that LLD prior to log transformation.	baseline (week 0) to week 6 (6 week period)
Primary	Relative Change in Lung Function	Relative change in FEV1 volume (L) from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6	baseline (week 0) to week 6 (6 week period)
Secondary	Relative Change in Lung Function	Relative change in FEV1 (L) from the beginning of the 4-week period with inhaled tobramycin at week 2 to the end of the 4-week period with inhaled tobramycin at week 6	week 2 to week 6 (4 week period)
Secondary	Change in Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS)	Absolute change in CFRSD-CRISS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. The Cystic Fibrosis Respiratory Symptoms Diary asks a participant to state the extent of 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest, and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present "a great deal" or "extremely." A summed score (ranging from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where lower scores indicate improvement of symptoms.	baseline (week 0) to week 6 (6 week period)
Secondary	Change in Cystic Fibrosis Questionnaire - Revised Respiratory Symptom Score (CFQ-R RSS)	Absolute change in the CFQ-R RSS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Age appropriate versions of Cystic Fibrosis Questionnaire - Revised ask a participant from 4 to 6 questions related to respiratory symptoms. The Respiratory Domain Scaled Score is calculated as follows: 100*[sum of {responses-1}] / [{number of responses}*3] only if [number of responses] = [number of possible responses]/2; otherwise the score is set to missing. The scaled score ranges from 0 to 100 and higher scores indicate improvement of symptoms.	baseline (week 0) to week 6 (6 week period)