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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
azithromycin
placebo (for azithromycin)
inhaled tobramycin
Sponsored by
Seattle Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital of Los Angeles
  • Stanford University Medical Center
  • Rady Children's Hospital and Health Center at the University of California San Diego
  • National Jewish Health
  • Yale University School of Medicine
  • University of Florida
  • The Nemours Children's Clinic - Orlando
  • Nemours Children's Clinic - Pensacola
  • Saint Luke's Cystic Fibrosis Center of Idaho
  • Northwestern University
  • Saint Francis Medical Center
  • Riley Hospital for Children
  • Maine Medical Partners Pediatric Specialty Care
  • Johns Hopkins University
  • Boston Children's Hospital
  • University of Massachusetts Memorial Health Care
  • University of Michigan Health System
  • Helen DeVos Children's Hospital
  • The Minnesota Cystic Fibrosis Center
  • Children's Mercy Kansas City
  • Cardinal Glennon Children's Medical Center
  • St. Louis Children's Hospital
  • Monmouth Medical Center
  • Beth Israel Medical Center
  • Children's Hospital of New York
  • University of Rochester Medical Center Strong Memorial
  • University of North Carolina at Chapel Hill
  • Cincinnati Children's Hospital Medical Center
  • University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital
  • Dayton Children's Hospital
  • Oregon Health Sciences University
  • Hershey Medical Center Pennsylvania State University
  • St. Christopher's Hospital for Children
  • Children's Hospital of Pittsburgh of UPMC
  • Cook Children's Medical Center
  • Intermountain Cystic Fibrosis Center
  • Seattle Children's Hospital
  • University of Washington Medical Center
  • Children's Hospital of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

azithromycin

placebo

Arm Description

azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks

encapsulated placebo taken by mouth thrice weekly for 6 weeks

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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.
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.

Full Information

First Posted
January 29, 2016
Last Updated
June 3, 2021
Sponsor
Seattle Children's Hospital
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Cystic Fibrosis Foundation, CF Therapeutics Development Network Coordinating Center
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1. Study Identification

Unique Protocol Identification Number
NCT02677701
Brief Title
Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
October 21, 2016 (Actual)
Primary Completion Date
February 13, 2020 (Actual)
Study Completion Date
February 13, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seattle Children's Hospital
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Cystic Fibrosis Foundation, CF Therapeutics Development Network Coordinating Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
119 (Actual)

8. Arms, Groups, and Interventions

Arm Title
azithromycin
Arm Type
Active Comparator
Arm Description
azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
encapsulated placebo taken by mouth thrice weekly for 6 weeks
Intervention Type
Drug
Intervention Name(s)
azithromycin
Other Intervention Name(s)
Zithromax
Intervention Description
500mg tablet over-encapsulated to match placebo
Intervention Type
Drug
Intervention Name(s)
placebo (for azithromycin)
Intervention Type
Drug
Intervention Name(s)
inhaled tobramycin
Intervention Description
clinically prescribed inhaled tobramycin used by subjects participating in the study
Primary Outcome Measure Information:
Title
Relative Change in Lung Function
Description
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
Time Frame
baseline (week 0) to week 6 (6 week period)
Secondary Outcome Measure Information:
Title
Relative Change in Lung Function
Description
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
Time Frame
week 2 to week 6 (4 week period)
Title
Change in Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS)
Description
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.
Time Frame
baseline (week 0) to week 6 (6 week period)
Title
Change in Cystic Fibrosis Questionnaire - Revised Respiratory Symptom Score (CFQ-R RSS)
Description
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.
Time Frame
baseline (week 0) to week 6 (6 week period)
Other Pre-specified Outcome Measures:
Title
Change in Sputum Pseudomonas Aeruginosa Bacterial Density
Description
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.
Time Frame
baseline (week 0) to week 6 (6 week period)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David P Nichols, MD
Organizational Affiliation
National Jewish Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94025
Country
United States
Facility Name
Rady Children's Hospital and Health Center at the University of California San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
The Nemours Children's Clinic - Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Nemours Children's Clinic - Pensacola
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
Saint Luke's Cystic Fibrosis Center of Idaho
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60208
Country
United States
Facility Name
Saint Francis Medical Center
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61637
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Maine Medical Partners Pediatric Specialty Care
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Massachusetts Memorial Health Care
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Helen DeVos Children's Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
The Minnesota Cystic Fibrosis Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Children's Mercy Kansas City
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Cardinal Glennon Children's Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Monmouth Medical Center
City
Long Branch
State/Province
New Jersey
ZIP/Postal Code
07740
Country
United States
Facility Name
Beth Israel Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Children's Hospital of New York
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester Medical Center Strong Memorial
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Dayton Children's Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45404
Country
United States
Facility Name
Oregon Health Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Hershey Medical Center Pennsylvania State University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
St. Christopher's Hospital for Children
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19134
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Intermountain Cystic Fibrosis Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98145
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

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

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