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

Phase 4
Completed
Conditions
Cystic Fibrosis
Interventions
Registration Number
NCT00431964
Lead Sponsor
CF Therapeutics Development Network Coordinating Center
Brief 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.

Detailed 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 & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
263
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Activeazithromycin 250 mg tabletsazithromycin 250 mg tablets
Placeboplacebo tabletsplacebo tablets (matched to active drug in appearance)
Primary Outcome Measures
NameTimeMethod
Change in FEV1 From Baseline to End of Treatment at Day 168change from baseline to day 168
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (40)

New York Medical College

🇺🇸

Valhalla, New York, United States

East Tennessee Children's Hospital, Pediatric Pulmonary & Respiratory Care

🇺🇸

Knoxville, Tennessee, United States

Vermont Children's Hospital

🇺🇸

Burlington, Vermont, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

The Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

St. Christopher's Hospital for Children

🇺🇸

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh, Pulmonary Medicine, Allergy & Immunology

🇺🇸

Pittsburgh, Pennsylvania, United States

Children's Memorial Hospital

🇺🇸

Chicago, Illinois, United States

Children's Hospital Boston

🇺🇸

Boston, Massachusetts, United States

Riley Hospital for Children

🇺🇸

Indianapolis, Indiana, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

Connecticut Children's Medical Center

🇺🇸

Hartford, Connecticut, United States

Alberta Children's Hospital

🇨🇦

Calgary, Alberta, Canada

Phoenix Children's Hospital

🇺🇸

Phoenix, Arizona, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

University of Nebraska Medical Center - Pediatric Pulmonary

🇺🇸

Omaha, Nebraska, United States

Cincinnati Children's Hospital

🇺🇸

Cincinnati, Ohio, United States

Vanderbilt Children's Hospital

🇺🇸

Nashville, Tennessee, United States

Children's Hospital of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

University of Utah Pediatric Pulmonology

🇺🇸

Salt Lake City, Utah, United States

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

Washington University

🇺🇸

St. Louis, Missouri, United States

Columbia University

🇺🇸

New York, New York, United States

Dartmouth Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

SUNY Upstate Medical University

🇺🇸

Syracuse, New York, United States

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

University of Tennessee Health Science Center

🇺🇸

Memphis, Tennessee, United States

University of Virginia at Charlottesville Children's Hospital

🇺🇸

Charlottesville, Virginia, United States

West Virginia University

🇺🇸

Morgantown, West Virginia, United States

BC Children's Hospital

🇨🇦

Vancouver, British Columbia, Canada

Janeway Children's Health & Rehabilitation Hospital

🇨🇦

St. John's, Newfoundland and Labrador, Canada

Bryan Lyttle, MD, Private Practice

🇨🇦

London, Ontario, Canada

Children's Hospital of Eastern Ontario

🇨🇦

Ottawa, Ontario, Canada

McMaster Health Sciences Centre

🇨🇦

Hamilton, Ontario, Canada

CSSS de Chicoutimi

🇨🇦

Chicoutimi, Quebec, Canada

Montreal Children's Hospital

🇨🇦

Montreal, Quebec, Canada

The Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

UNC Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

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