Clinical trial NCT00431964: Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cystic Fibrosis
Keywords: azithromycin, Zithromax
Lead sponsor: CF Therapeutics Development Network Coordinating Center
Sponsor class: NETWORK
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2007-02-06
Enrollment: 263
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Change in FEV1 From Baseline to End of Treatment at Day 168
timeFrame: change from baseline to day 168
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center - Pediatric Pulmonary
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh, Pulmonary Medicine, Allergy & Immunology
state: Pennsylvania
city: Knoxville
country: United States
facility: East Tennessee Children's Hospital, Pediatric Pulmonary & Respiratory Care
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah Pediatric Pulmonology
state: Utah
city: Burlington
country: United States
facility: Vermont Children's Hospital
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia at Charlottesville Children's Hospital
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: St. John's
country: Canada
facility: Janeway Children's Health & Rehabilitation Hospital
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: McMaster Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: Bryan Lyttle, MD, Private Practice
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Chicoutimi
country: Canada
facility: CSSS de Chicoutimi
state: Quebec
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
Study officials:
affiliation: Columbia University
name: Lisa Saiman, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kentucky
name: Michael Anstead, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hospital for Sick Children, Toronto, Ontario
name: Felix Ratjen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montreal Children's Hospital of the MUHC
name: Larry Lands, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.