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

Condition(s) targeted: Cystic Fibrosis

Intervention: azithromycin 250 mg tablets (Drug); placebo tablets (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: CF Therapeutics Development Network Coordinating Center

Official(s) and/or principal investigator(s):
Lisa Saiman, MD, MPH, Principal Investigator, Affiliation: Columbia University
Michael Anstead, MD, Principal Investigator, Affiliation: University of Kentucky
Felix Ratjen, MD, Principal Investigator, Affiliation: The Hospital for Sick Children, Toronto, Ontario
Larry Lands, MD, Principal Investigator, Affiliation: Montreal Children's Hospital

Overall contact:
Jasna Hocevar-Trnka, MPH, Phone: 206-884-7527, Email: jasna.hocevar-trnka@seattlechildrens.org

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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Primary outcome: Change in FEV1 from baseline to end of treatment

Secondary outcome: Safety, frequency of pulmonary exacerbations, changes in other measures of lung function, treatment emergent pathogens, weight, and serum inflammatory markers

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.

Minimum age: 6 Years. Maximum age: 18 Years. Gender(s): Both.

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

Jasna Hocevar-Trnka, MPH, Phone: 206-884-7527, Email: jasna.hocevar-trnka@seattlechildrens.org

Alberta Children's Hospital, Calgary, Alberta T3B 6A8, Canada; Active, not recruiting

Phoenix Children's Hospital, Phoenix, Arizona 85016, United States; Recruiting
Natalia Argel, Phone: 602-546-0343, Email: nargel@phoenixchildrens.com
Peggy J. Radford, MD, Principal Investigator

BC Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada; Active, not recruiting

Connecticut Children's Medical Center, Hartford, Connecticut 06106, United States; Active, not recruiting

Emory University, Atlanta, Georgia 30322, United States; Recruiting
Jeannie Peabody, Phone: 404-712-3930, Email: jmpeabo@emory.edu
Michael Schechter, MD, Principal Investigator

Children's Memorial Hospital, Chicago, Illinois 60614, United States; Active, not recruiting

Riley Hospital for Children, Indianapolis, Indiana 46202, United States; Recruiting
Toni Smith, Phone: 317-278-7121, Email: tlsmith@iupui.edu
Michelle S. Howenstine, MD, Principal Investigator

University of Kentucky, Lexington, Kentucky 40536, United States; Recruiting
Barbara Owsley, Phone: 859-257-5087, Email: barbara.owsley@uky.edu
Michael Anstead, MD, Principal Investigator

Children's Hospital Boston, Boston, Massachusetts 02115, United States; Recruiting
Summer Gulley, Phone: 617-355-2446, Email: summer.adamsgulley@childrens.harvard.edu
Lindo Terry Spencer, MD, Principal Investigator

University of Michigan, Ann Arbor, Michigan 48109, United States; Recruiting
Sharon Stetz, Phone: 734-936-3340, Email: spstetz@umich.edu
Samya Z. Nasr, MD, Principal Investigator

University of Minnesota, Minneapolis, Minnesota 55455, United States; Active, not recruiting

Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Active, not recruiting

Washington University, St. Louis, Missouri 63110, United States; Not yet recruiting
Mary Boyle, Phone: 314-454-4609, Email: boyle@kids.wustl.edu
Albert Faro, MD, Principal Investigator

University of Nebraska Medical Center - Pediatric Pulmonary, Omaha, Nebraska 68198, United States; Recruiting
Deb Heimes, Phone: 402-559-8870, Email: dheimes@unmc.edu
John Colombo, MD, Principal Investigator

Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States; Recruiting
Nicola Felicetti, Phone: 603-653-9884, Email: nicola.j.felicetti@hitchcock.org
H. Worth Parker, MD, Principal Investigator

SUNY Upstate Medical University, Syracuse, New York 13210, United States; Recruiting
Valoree Suttmore, Phone: 315-464-7593, Email: suttmorv@upstate.edu
Ran Anbar, MD, Principal Investigator

New York Medical College, Valhalla, New York 10595, United States; Recruiting
Ingrid Gherson, Phone: 914-594-3320, Email: ingrid_gherson@nymc.edu
Allen J. Dozor, MD, Principal Investigator

University of Rochester Medical Center, Rochester, New York 14642, United States; Recruiting
Marissa Dixon, Phone: 585-275-8580, Email: Marissa_Dixon@urmc.rochester.edu
Clement L. Ren, MD, Principal Investigator

Columbia University, New York, New York 10032, United States; Active, not recruiting

Janeway Children's Health & Rehabilitation Hospital, St. John's, Newfoundland and Labrador A1B 3V6, Canada; Recruiting
Kimberley Manning, Phone: 709-777-4905, Email: kimberleyannemanning@hotmail.com
Sharon Penney, Phone: 709-777-4905, Email: sharonj.penney@easternhealth.ca
Mary E. Noseworthy, MD, Principal Investigator

UNC Chapel Hill, Chapel Hill, North Carolina 27599, United States; Recruiting
Caroline O'Connor, Phone: 919-843-7121, Email: coconnor@med.unc.edu
George Retsch-Bogart, MD, Principal Investigator

Cincinnati Children's Hospital, Cincinnati, Ohio 45229, United States; Recruiting
Lorrie Duan, Phone: 513-636-7089, Email: lorrie.duan@cchmc.org
James D. Acton, MD, Principal Investigator

Nationwide Children's Hospital, Columbus, Ohio 43205, United States; Recruiting
Christine Hapanowicz, Phone: 614-722-2605, Email: Christine.Hapanowicz@NationwideChildrens.org
Karen McCoy, MD, Principal Investigator

McMaster Health Sciences Centre, Hamilton, Ontario L8N 3Z5, Canada; Recruiting
Rosamund Hennessey, Phone: 905-912-2212, Email: hennesr@mcmaster.ca
Linda Pedder, MD, Principal Investigator

Bryan Lyttle, MD, Private Practice, London, Ontario N6A 5B8, Canada; Active, not recruiting

Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada; Recruiting
Anne Smith, Phone: 613-737-7600, Ext: 2214, Email: smith_a@cheo.on.ca
Tom Kovesi, MD, Principal Investigator

The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada; Recruiting
Sean Martin, Phone: 416-813-7654, Ext: 2016, Email: sean.martin@sickkids.ca
Felix Ratjen, MD, Principal Investigator

Children's Hospital of Pittsburgh, Pulmonary Medicine, Allergy & Immunology, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Elizabeth Hartigan, Phone: 412-692-7060, Email: elizabeth.hartigan@chp.edu
Jonathan Finder, MD, Principal Investigator

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134, United States; Recruiting
Justin Overcash, Phone: 215-427-3816, Email: justin.overcash@tenethealth.com
Laurie Varlotta, MD, Principal Investigator

The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
Ruth Bradford, Phone: 267-426-5747, Email: bradford@email.chop.edu
Ronald C. Rubenstein, MD, Principal Investigator

CSSS de Chicoutimi, Chicoutimi, Quebec G7H 5H6, Canada; Recruiting
Chantal Martineau, Phone: 418-541-1037, Email: fksagamie@ssss.gouv.qc.ca
Marcel Milot, MD, Principal Investigator

Montreal Children's Hospital, Montreal, Quebec H3H 1P3, Canada; Active, not recruiting

East Tennessee Children's Hospital, Pediatric Pulmonary & Respiratory Care, Knoxville, Tennessee 37916, United States; Active, not recruiting

University of Tennessee Health Science Center, Memphis, Tennessee 38105, United States; Recruiting
Barbara Culbreath, RN, CCRC, Phone: 901-287-5340, Email: bculbreath@utmem.edu
Dennis C. Stokes, MD, Principal Investigator

Vanderbilt Children's Hospital, Nashville, Tennessee 37232, United States; Recruiting
Michelle Robinette, Phone: 615-343-9025, Email: michelle.robinette@vanderbilt.edu
Elizabeth Perkett, MD, Principal Investigator

University of Utah Pediatric Pulmonology, Salt Lake City, Utah 84108, United States; Recruiting
Jane Vroom, Phone: 801-587-7458, Email: jane.vroom@hsc.utah.edu
Barbara Chatfield, MD, Principal Investigator

Vermont Children's Hospital, Burlington, Vermont 05401, United States; Recruiting
Emily Keller, Phone: 802-847-8600, Email: emily.keller@vtmednet.org
Thomas Lahiri, MD, Principal Investigator

University of Virginia at Charlottesville Children's Hospital, Charlottesville, Virginia 22908, United States; Recruiting
Robin Kelly, Phone: 434-243-2876, Email: rlk5a@virginia.edu
Deborah Froh, MD, Principal Investigator

West Virginia University, Morgantown, West Virginia 26506, United States; Recruiting
Sue Collins, Phone: 304-293-7374, Email: scollins@hsc.wvu.edu
Kathryn S. Moffett, MD, Principal Investigator

Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States; Recruiting
Brilliant Nimmer, Phone: 414-266-6986, Email: bnimmer@ncw.edu
Diana Quintero, MD, Principal Investigator

Starting date: February 2007
Ending date: March 2010
Last updated: September 29, 2008