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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: azithromycin 250 mg tablets; Drug: placebo tablets

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.

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active; 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 Names: Zithromax
Placebo Comparator: Placebo; 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 Names: inactive pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in FEV1 From Baseline to End of Treatment at Day 168	change from baseline to day 168

Collaborators and Investigators

• Sponsor: CF Therapeutics Development Network Coordinating Center
• Collaborators: 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

Publications and helpful links

General Publications

• 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 Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2010 May 5;303(17):1707-15. doi: 10.1001/jama.2010.563.
• Ratjen F, Saiman L, Mayer-Hamblett N, Lands LC, Kloster M, Thompson V, Emmett P, Marshall B, Accurso F, Sagel S, Anstead M. Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa. Chest. 2012 Nov;142(5):1259-1266. doi: 10.1378/chest.12-0628.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: February 2, 2007
• First Submitted That Met QC Criteria: February 2, 2007
• First Posted (Estimate): February 6, 2007

Study Record Updates

• Last Update Posted (Estimate): August 19, 2015
• Last Update Submitted That Met QC Criteria: July 24, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: azithromycin, Zithromax
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: AZ0004