Cystic fibrosis (CF) is a chronic disease that significantly affects an individual's lung
function. Antibiotic medications have been proven effective at reducing Pseudomonas
aeruginosa (PA) infection, which is one of the main causes of death in individuals with CF.
The purpose of this study is to compare the effectiveness of treatment based on quarterly
culture results versus consistent quarterly antibiotic treatment at reducing PA infection in
children with CF.
This 18-month study will enroll children with CF. For the first 28 days of the study, all
participants will receive inhaled tobramycin. For the initial 14 days of this 28-day period,
half of the participants will also receive either ciprofloxacin or placebo. If respiratory
cultures after three weeks of treatment confirm the presence of PA, participants will receive
tobramycin for an additional 28 days. Participants will then be randomly assigned to one of
four treatment options: tobramycin and placebo for six consecutive quarterly cycles;
tobramycin and ciprofloxacin for six consecutive quarterly cycles; tobramycin and placebo
only when PA is found during quarterly respiratory cultures; or tobramycin and ciprofloxacin
only when PA is found during quarterly respiratory cultures.
At the first study visit, participants will undergo a physical examination, a chest x-ray,
and a review of their medical history. Lung function will be measured via spirometry (in
children greater than four years of age who are able to perform spirometry), and hearing
ability will be measured via audiometry (at selected sites). Blood will be drawn for
laboratory tests, and a specimen will be obtained for a respiratory culture. Subsequent study
visits will take place at Day 21, Weeks 10, 22, 34, 46, 58, and 70. At each visit,
participants will undergo a physical examination and a spirometry test (as appropriate), and
a respiratory specimen for PA culture and blood will again be collected. Participants will be
required to maintain a medication diary throughout the study, and they will be contacted
between visits to review medication adherence and test results.
Inclusion Criteria:
- Diagnosis of CF, as determined by the 1997 CF Consensus Conference criteria: sweat
chloride level greater than 60 mEq/L by quantitative pilocarpine iontophoresis; or a
genotype with two identifiable mutations consistent with CF; or an abnormal nasal
transepithelial potential difference and one or more clinical features consistent with
CF
- For participants greater than 15 months of age: documented new onset of positive
oropharyngeal, sputum, or lower respiratory tract culture for PA within 6 months of
study entry, defined as either: 1) first lifetime documented PA positive culture; or
2) PA recovered after at least a 2-year history of PA negative respiratory cultures
(at least one culture per year)
- For participants 12-15 months of age: at least one documented positive oropharyngeal,
sputum, or lower respiratory tract culture for PA since birth or CF diagnosis
- Clinically stable with no evidence of any significant respiratory symptoms or chest
radiograph findings at screening that would require administration of intravenous
anti-pseudomonal antibiotics, oxygen supplementation, or hospitalization
Exclusion Criteria:
- History of aminoglycoside hypersensitivity or adverse reaction to inhaled
aminoglycoside
- History of hypersensitivity or adverse reaction to ciprofloxacin or other
fluoroquinolone medications
- History of persistent, unresolved hearing loss documented by audiometric testing on at
least two occasions and not associated with middle ear disease or an abnormal
tympanogram
- Abnormal kidney function at study entry (defined as a serum creatinine level greater
than 1. 5 times the upper limit of normal for participant's age)
- Abnormal liver function test results at study entry (defined as ALT and/or AST levels
greater than two times the upper limit of normal range)
- Use of any investigational drug within 30 days of study entry
- Use of loop diuretics, phenytoin, warfarin, theophylline, or other methylxanthines
within 30 days of study entry
- Use of more than one course of intravenous anti-pseudomonal antibiotics (at least 10
continuous days of medication use) or more than one course of inhaled anti-pseudomonal
antibiotics (at least 28 continuous days of medication use) within 2 years of study
entry; intravenous or inhaled anti-pseudomonal antibiotics must be stopped at least 30
days prior to study entry
- Chronic macrolide use (more than 90 day duration) in the 3 months prior to study
entry
- Presence of a condition or abnormality that would compromise the participant's safety
or the quality of the study data, in the opinion of the investigator
University of Alabama at Birmingham, Birmingham, Alabama 35233, United States
Northern California Kaiser Cystic Fibrosis Center, Oakland, California 94611, United States
Stanford University, Palo Alto, California 94304-5786, United States
University of California, San Francisco, San Francisco, California 94143, United States
Children's Hospital of Los Angeles, Los Angeles, California 90027, United States
Children's Hospital Denver, Aurora, Colorado 80045, United States
duPont Hospital for Children, Wilmington, Delaware 19803, United States
Nemours Children's Clinic, Jacksonville, Florida 32207, United States
All Children's Hospital Cystic Fibrosis Center, St. Petersburg, Florida 33701, United States
Emory University Cystic Fibrosis Center, Atlanta, Georgia 30322, United States
Medical College of Georgia, Augusta, Georgia 30912, United States
Children's Memorial Hospital, Chicago, Illinois 60614, United States
Riley Hospital/Indiana University, Indianapolis, Indiana 46202, United States
University of Iowa, Iowa City, Iowa 52242, United States
University of Kentucky, Lexington, Kentucky 40536-0284, United States
Maine Medical Center, Portland, Maine 04102, United States
Johns Hopkins University, Baltimore, Maryland 21287, United States
Children's Hospital, Boston, Boston, Massachusetts 02115, United States
Massachusetts General Hospital, Boston, Massachusetts 02114, United States
University of Massachusetts Memorial Health Care, Worcester, Massachusetts 06155, United States
University of Michigan, Ann Arbor, Michigan 48109-0212, United States
Spectrum Health Hospitals - DeVos Children's, Grand Rapids, Michigan 49503, United States
Children's Hospital of Michigan, Detroit, Michigan 48201, United States
Children's Hospitals & Clinics, Minneapolis, Minnesota 55102, United States
University of Mississippi Medical Center, Jackson, Mississippi 39216, United States
Children's Mercy Hospital, Kansas City, Missouri 64108, United States
Washington University School of Medicine, St. Louis, Missouri 63110, United States
Cardinal Glennon Children's Hospital, St. Louis, Missouri 63104, United States
University of Nebraska, Omaha, Nebraska 68198-5190, United States
Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0001, United States
Monmouth Medical Center, Long Branch, New Jersey 07740, United States
Albany Medical College, Albany, New York 12208, United States
University of Rochester, Rochester, New York 14642, United States
State University of New York Upstate Medical University, Syracuse, New York 13210, United States
New York Medical College, Valhalla, New York 10595, United States
University of North Carolina, Chapel Hill, Chapel Hill, North Carolina 27599, United States
Children's Hospital Medical Center of Akron, Akron, Ohio 44308, United States
Rainbow Babies & Children's Hospital, Cleveland, Ohio 44106, United States
Children's Hospital, Columbus, Ohio 43205, United States
Children's Medical Center, Dayton, Ohio 45404, United States
Oregon Health Sciences University, Portland, Oregon 97239, United States
Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, United States
St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
LeBonheur Children's Medical Center, Memphis, Tennessee 38105, United States
Vanderbilt University Medical Center, Nashville, Tennessee 37232-9500, United States
Cook Children's Medical Center, Ft. Worth, Texas 76104, United States
Texas Children's Hospital, Houston, Texas 77030, United States
University of Utah, Salt Lake City, Utah 84106, United States
Vermont Children's Hospital at Fletcher Allen Health Care, Burlington, Vermont 05401, United States
University of Virginia, Charlottesville, Virginia 22908, United States
Children's Hospital & Regional Medical Center, Seattle, Washington 98105, United States
University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, United States
Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States
