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Comparison of Two Treatment Regimens to Reduce PA Infection in Children With Cystic Fibrosis

Information source: Seattle Children's Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Cystic Fibrosis; Pulmonary Disease, Chronic Obstructive

Intervention: Tobramycin solution for inhalation (TOBI) (Drug); Oral placebo (Drug); Oral ciprofloxacin (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Seattle Children's Hospital

Official(s) and/or principal investigator(s):
Bonnie W. Ramsey, Principal Investigator, Affiliation: University of Washington
George Retsch-Bogart, MD, Principal Investigator, Affiliation: University of North Carolina, Chapel Hill
Miriam Treggiari, MD, Principal Investigator, Affiliation: University of Washington

Summary

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.

Clinical Details

Official title: Effectiveness and Safety of Intermittent Antimicrobial Therapy for the Treatment of New Onset Pseudomonas Aeruginosa Airway Infection in Young Patients With Cystic Fibrosis

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: Number of Participants With a Pulmonary Exacerbation Requiring IV Antibiotics or Hospitalization

Secondary outcome:

Proportion of Participants With a Pa Positive Culture

Number of Participants With a Pulmonary Exacerbation Requiring Oral, Inhaled, or Oral Antibiotics

Detailed description: CF is an inherited disease that causes mucus to build up in the lungs and digestive tract, which can cause lung infections and digestive problems. It is the most common type of chronic lung disease in children and young adults and may result in early death. There is no cure for this disease. The primary cause of death in individuals with CF is progressive obstructive pulmonary disease associated with chronic Pseudomonas aeruginosa (PA) infection. PA infection can occur early in life and can become highly resistant to antibiotics. Once an individual has been diagnosed with chronic PA infection, it is almost impossible to manage effectively. The need exists for an effective treatment to control and eliminate PA infection. Past research has shown that if PA infection is treated early, there is a greater likelihood that it may be eliminated completely. This study will examine two treatment regimens to compare which is more effective at eliminating PA infection. In the first regimen, participants will receive antibiotic treatment at various times throughout the study, based on findings of PA respiratory cultures obtained on a quarterly basis. In the second regimen, participants will receive antibiotic medications in consistent, quarterly cycles throughout the study. The antibiotic medications used in this study will be ciprofloxacin and inhaled tobramycin, which will be administered with a nebulizer. Both of these medications have been proven effective at treating bacterial lung infections. The overall purpose of this study is to compare the effectiveness of culture-based treatment versus consistent 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.

Eligibility

Minimum age: 1 Year. Maximum age: 12 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of CF, as determined by the 1997 CF Consensus Conference criteria: sweat

chloride level greater than 60 milliequivalent/liter (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 alanine

aminotransferase (ALT) and/or aspartate aminotransferase (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

Locations and Contacts

University of Alabama at Birmingham, Birmingham, Alabama 35233, United States

Children's Hospital of Los Angeles, Los Angeles, California 90027, 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 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

Children's Hospital of Michigan, Detroit, Michigan 48201, United States

Spectrum Health Hospitals - DeVos Children's, Grand Rapids, Michigan 49503, 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

Cardinal Glennon Children's Hospital, St. Louis, Missouri 63104, United States

Washington University School of Medicine, St. Louis, Missouri 63110, 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

Additional Information

Related publications:

Treggiari MM, Rosenfeld M, Mayer-Hamblett N, Retsch-Bogart G, Gibson RL, Williams J, Emerson J, Kronmal RA, Ramsey BW; EPIC Study Group. Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study'. Contemp Clin Trials. 2009 May;30(3):256-68. doi: 10.1016/j.cct.2009.01.003. Epub 2009 Jan 15.

Starting date: September 2004
Last updated: January 28, 2014

Page last updated: August 23, 2015

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