Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa

Cystic Fibrosis Clinical Trial

Official title:

Multi-center, Multi-national, Randomized, Placebo-Controlled Trial of Azithromycin in Subjects With Cystic Fibrosis 6-18 Years Old, Culture Negative for Pseudomonas Aeruginosa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00431964
• Other study ID #: AZ0004
• Status: Completed
• Phase: Phase 4
• First received: February 2, 2007
• Last updated: July 24, 2015
• Start date: February 2007
• Est. completion date: November 2009

Study information

• Verified date: July 2015
• Source: CF Therapeutics Development Network Coordinating Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

This is a study to examine the safety, effect on lung function, and frequency of symptoms relating to cystic fibrosis during 24 weeks of treatment with the antibiotic azithromycin in 6-18 year-olds with CF who are not infected with Pseudomonas aeruginosa.

Description:

Azithromycin is an antibiotic that has been shown to improve lung function in patients with cystic fibrosis (CF) whose lungs are infected with a bacterium called Pseudomonas aeruginosa. Scientists are not sure how azithromycin works in cystic fibrosis. It does not appear to work by killing the bacteria Pseudomonas aeruginosa, but it may make these bacteria and other bacteria less damaging to the lungs by reducing their ability to attach to the lining of the lung, or by reducing the bacteria's ability to make substances that damage the lungs of patients with cystic fibrosis. Azithromycin may also work directly on the cells in the lungs to improve lung function. This could occur by reducing inflammation (swelling) in the lungs, and/or making the mucus less sticky, or by affecting the salt channel that doesn't function correctly in CF. If azithromycin works in one or more of these ways; it may also be effective in improving lung function in cystic fibrosis patients who are not infected with Pseudomonas aeruginosa.

We are conducting this research study to examine the safety, effect on lung function and frequency of symptoms relating to cystic fibrosis during 24 weeks of treatment with the antibiotic azithromycin. This study is designed to determine if patients with cystic fibrosis whose lungs are not infected with the bacteria Pseudomonas aeruginosa will benefit from 24 weeks of treatment with the antibiotic azithromycin. Benefit will be determined as having better pulmonary function tests and getting sick less often compared to a placebo (sugar pill). This study is also designed to determine if azithromycin is safe when administered for 24 weeks to cystic fibrosis patients not infected with Pseudomonas aeruginosa. By doing this study, we hope to learn more about CF and improve the way in which we treat it.

Comparison: Three times weekly azithromycin tablets added to standard care, compared to three times weekly placebo tablets added to standard care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 263
• Est. completion date: November 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 18 Years

Eligibility

Inclusion Criteria:

• Male or female, 6-18 years of age at enrollment

• Confirmed diagnosis of CF

• Written informed consent (and assent when applicable)

• Clinically stable at enrollment as assessed by the site investigator

• FEV1 % predicted > 50%

• Ability to comply with medication use, study visits, and study procedures

• Ability to swallow a 250 mg tablet

Exclusion Criteria:

• Weight less than 18.0 kg

• Respiratory culture positive for P. aeruginosa, NTM, or B. cepacia complex within 1 year or at screening, or AFB positive at screening

• Allergy to macrolide antibiotics

• Use of macrolide antibiotics (e.g., azithromycin, clarithromycin) within 60 days of screening

• Use of systemic corticosteroids or intravenous or oral antibiotics within 14 days of screening

• Initiation of high dose ibuprofen, Pulmozyme®, hypertonic saline or aerosolized antibiotics within 30 days of screening

• Chronic therapy with drugs known to have rare but serious interactions with azithromycin: amiodarone, digoxin, disopyramide, lovastatin, pimozide, rifabutin, and nelfinavir

• Investigational drug use within 30 days of screening

• Laboratory abnormalities (creatinine, liver function or neutropenia) at screening and confirmed at follow-up testing prior to randomization

• History of biliary cirrhosis, portal hypertension, or splenomegaly, or splenomegaly on physical exam

• History of ventricular arrhythmia

• Other major organ dysfunction, excluding pancreatic dysfunction

• History of lung transplantation or currently on lung transplant list

• Relative decrease in FEV1 % predicted = 20% between the screening and enrollment visit

• Positive serum pregnancy test at screening

• Pregnant, breastfeeding, or if post-menarche female, unwilling to practice birth control during participation in the study

• History of alcohol, illicit drug or medication abuse within 1 year of screening in the judgment of the site investigator

• Presence of a condition or abnormality that in the opinion of the site investigator would compromise the safety of the subject or the quality of the data

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• azithromycin 250 mg tablets
One (1) tablet three times weekly for patients who weigh 40-79 lbs Two (2) tablets three times weekly for patients who weigh greater than or equal to 80 lbs
• placebo tablets
One (1) tablet three times weekly for patients who weigh 40-79 lbs Two (2) tablets three times weekly for patients who weigh greater than or equal to 80 lbs

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	CSSS de Chicoutimi	Chicoutimi	Quebec
Canada	McMaster Health Sciences Centre	Hamilton	Ontario
Canada	Bryan Lyttle, MD, Private Practice	London	Ontario
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Janeway Children's Health & Rehabilitation Hospital	St. John's	Newfoundland and Labrador
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	BC Children's Hospital	Vancouver	British Columbia
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Vermont Children's Hospital	Burlington	Vermont
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia at Charlottesville Children's Hospital	Charlottesville	Virginia
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Children's Hospital, Pediatric Pulmonary & Respiratory Care	Knoxville	Tennessee
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	University of Nebraska Medical Center - Pediatric Pulmonary	Omaha	Nebraska
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh, Pulmonary Medicine, Allergy & Immunology	Pittsburgh	Pennsylvania
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Utah Pediatric Pulmonology	Salt Lake City	Utah
United States	Washington University	St. Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	New York Medical College	Valhalla	New York

Sponsors (2)

Lead Sponsor	Collaborator
CF Therapeutics Development Network Coordinating Center	Cystic Fibrosis Foundation Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Saiman L, Anstead M, Mayer-Hamblett N, Lands LC, Kloster M, Hocevar-Trnka J, Goss CH, Rose LM, Burns JL, Marshall BC, Ratjen F; AZ0004 Azithromycin Study Group. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in FEV1 From Baseline to End of Treatment at Day 168		change from baseline to day 168	Yes