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

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
CF Therapeutics Development Network Coordinating Center
ClinicalTrials.gov Identifier:
NCT00431964
First received: February 2, 2007
Last updated: February 11, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Drug: azithromycin 250 mg tablets
Drug: placebo tablets
Phase 4

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

Resource links provided by NLM:


Further study details as provided by CF Therapeutics Development Network Coordinating Center:

Primary Outcome Measures:
  • Change in FEV1 from baseline to end of treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety, frequency of pulmonary exacerbations, changes in other measures of lung function, treatment emergent pathogens, weight, and serum inflammatory markers [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 263
Study Start Date: February 2007
Study Completion Date: November 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
azithromycin 250 mg tablets
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
Other Name: Zithromax
Placebo Comparator: 2
placebo tablets (matched to active drug in appearance)
Drug: 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
Other Name: inactive pill

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.

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00431964

  Hide Study Locations
Locations
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Washington University
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center - Pediatric Pulmonary
Omaha, Nebraska, United States, 68198
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Columbia University
New York, New York, United States, 10032
University of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
UNC Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
Children's Hospital of Pittsburgh, Pulmonary Medicine, Allergy & Immunology
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
East Tennessee Children's Hospital, Pediatric Pulmonary & Respiratory Care
Knoxville, Tennessee, United States, 37916
University of Tennessee Health Science Center
Memphis, Tennessee, United States, 38105
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232
United States, Utah
University of Utah Pediatric Pulmonology
Salt Lake City, Utah, United States, 84108
United States, Vermont
Vermont Children's Hospital
Burlington, Vermont, United States, 05401
United States, Virginia
University of Virginia at Charlottesville Children's Hospital
Charlottesville, Virginia, United States, 22908
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Canada, British Columbia
BC Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Newfoundland and Labrador
Janeway Children's Health & Rehabilitation Hospital
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
McMaster Health Sciences Centre
Hamilton, Ontario, Canada, L8N 3Z5
Bryan Lyttle, MD, Private Practice
London, Ontario, Canada, N6A 5B8
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
CSSS de Chicoutimi
Chicoutimi, Quebec, Canada, G7H 5H6
Montreal Children's Hospital
Montreal, Quebec, Canada, H3H 1P3
Sponsors and Collaborators
CF Therapeutics Development Network Coordinating Center
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Lisa Saiman, MD, MPH Columbia University
Principal Investigator: Michael Anstead, MD University of Kentucky
Principal Investigator: Felix Ratjen, MD The Hospital for Sick Children, Toronto, Ontario
Principal Investigator: Larry Lands, MD Montreal Children's Hospital of the MUHC
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: CF Therapeutics Development Network Coordinating Center
ClinicalTrials.gov Identifier: NCT00431964     History of Changes
Other Study ID Numbers: AZ0004
Study First Received: February 2, 2007
Last Updated: February 11, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Canada: Health Canada

Keywords provided by CF Therapeutics Development Network Coordinating Center:
azithromycin, Zithromax

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014