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

Sponsor:	CF Therapeutics Development Network Coordinating Center
Collaborator:	Cystic Fibrosis Foundation
Information provided by (Responsible Party):	CF Therapeutics Development Network Coordinating Center
ClinicalTrials.gov Identifier:	NCT00431964

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:

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Azithromycin Azithromycin dihydrate Azithromycin monohydrate Pseudomonas aeruginosa

U.S. FDA Resources

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

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

Show 40 Study Locations

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

More Information

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.

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 8, 2012
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 May 24, 2012