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

NCT ID: NCT00431964

Last Updated: 2015-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 263 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2009-11-30

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active

azithromycin 250 mg tablets

Group Type: ACTIVE_COMPARATOR

azithromycin 250 mg tablets

Intervention Type: DRUG

• 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

Placebo

placebo tablets (matched to active drug in appearance)

Group Type: PLACEBO_COMPARATOR

placebo tablets

Intervention Type: DRUG

• 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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Zithromax; inactive pill

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cystic Fibrosis Foundation

OTHER

Sponsor Role: collaborator

CF Therapeutics Development Network Coordinating Center

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa Saiman, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Michael Anstead, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Felix Ratjen, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children, Toronto, Ontario

Larry Lands, MD

Role: PRINCIPAL_INVESTIGATOR

Montreal Children's Hospital of the MUHC

Locations

Phoenix Children's Hospital

Phoenix, Arizona, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Emory University

Atlanta, Georgia, United States

Children's Memorial Hospital

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

University of Kentucky

Lexington, Kentucky, United States

Children's Hospital Boston

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Washington University

St Louis, Missouri, United States

University of Nebraska Medical Center - Pediatric Pulmonary

Omaha, Nebraska, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Columbia University

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

New York Medical College

Valhalla, New York, United States

UNC Chapel Hill

Chapel Hill, North Carolina, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh, Pulmonary Medicine, Allergy & Immunology

Pittsburgh, Pennsylvania, United States

East Tennessee Children's Hospital, Pediatric Pulmonary & Respiratory Care

Knoxville, Tennessee, United States

University of Tennessee Health Science Center

Memphis, Tennessee, United States

Vanderbilt Children's Hospital

Nashville, Tennessee, United States

University of Utah Pediatric Pulmonology

Salt Lake City, Utah, United States

Vermont Children's Hospital

Burlington, Vermont, United States

University of Virginia at Charlottesville Children's Hospital

Charlottesville, Virginia, United States

West Virginia University

Morgantown, West Virginia, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Alberta Children's Hospital

Calgary, Alberta, Canada

BC Children's Hospital

Vancouver, British Columbia, Canada

Janeway Children's Health & Rehabilitation Hospital

St. John's, Newfoundland and Labrador, Canada

McMaster Health Sciences Centre

Hamilton, Ontario, Canada

Bryan Lyttle, MD, Private Practice

London, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

CSSS de Chicoutimi

Chicoutimi, Quebec, Canada

Montreal Children's Hospital

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 20442386 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22595153 (View on PubMed)

Other Identifiers

AZ0004

Identifier Type: -

Identifier Source: org_study_id