Comparison of Two Treatment Regimens to Reduce PA Infection in Children With Cystic Fibrosis
EPIC
Effectiveness and Safety of Intermittent Antimicrobial Therapy for the Treatment of New Onset Pseudomonas Aeruginosa Airway Infection in Young Patients With Cystic Fibrosis
2 other identifiers
interventional
304
1 country
54
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2004
Longer than P75 for phase_2
54 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2004
CompletedFirst Submitted
Initial submission to the registry
November 30, 2004
CompletedFirst Posted
Study publicly available on registry
December 1, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2009
CompletedResults Posted
Study results publicly available
November 7, 2013
CompletedFebruary 28, 2014
January 1, 2014
4.8 years
November 30, 2004
June 11, 2013
January 28, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With a Pulmonary Exacerbation Requiring IV Antibiotics or Hospitalization
The primary comparison is between the pooled culture-based group and the pooled cycled group. A secondary comparison is between the pooled ciprofloxacin group vs the pooled placebo group. Descriptive results are provided for the pooled treatment groups. Participants are represented once in the cycled and culture-based therapy columns, and once in the cipro and placebo columns.
Measured over the 18 month study
Secondary Outcomes (2)
Proportion of Participants With a Pa Positive Culture
Week 10 (after initial treatment course for Pa) through Month 18
Number of Participants With a Pulmonary Exacerbation Requiring Oral, Inhaled, or Oral Antibiotics
Measured over the 18 month time period
Study Arms (4)
Cycled TOBI & placebo
PLACEBO COMPARATORTobramycin inhalation solution and oral placebo for six consecutive quarterly cycles
Cycled TOBI & oral ciprofloxacin
ACTIVE COMPARATORTobramycin solution for inhalation and oral ciprofloxacin for six consecutive quarterly cycles.
Culture based TOBI & placebo
PLACEBO COMPARATORTobramycin solution for inhalation and oral placebo administered only when quarterly respiratory cultures are found positive for Pa.
Culture based TOBI & oral cipro
ACTIVE COMPARATORTobramycin solution for inhalation and oral ciprofloxacin administered only when quarterly respiratory cultures are found positive for Pa.
Interventions
Tobramycin solution for inhalation, 300 mg, administered twice daily for 28 days administered only when quarterly respiratory cultures are found positive for Pa.
Oral placebo for six consecutive quarterly cycles. For the initial 14 days of the 28-day treatment period, the participants will receive placebo, twice daily.
Oral ciprofloxacin for six consecutive quarterly cycles. For the initial 14 days of the 28-day treatment period, the participants will receive oral ciprofloxacin, 15-20 mg/kg/dose, twice daily.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Seattle Children's Hospitallead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- Cystic Fibrosis Foundationcollaborator
- CF Therapeutics Development Network Coordinating Centercollaborator
Study Sites (54)
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
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Children's Hospital, Boston
Boston, Massachusetts, 02115, 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
Fort 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
Related Publications (4)
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.
PMID: 19470318BACKGROUNDTreggiari MM, Retsch-Bogart G, Mayer-Hamblett N, Khan U, Kulich M, Kronmal R, Williams J, Hiatt P, Gibson RL, Spencer T, Orenstein D, Chatfield BA, Froh DK, Burns JL, Rosenfeld M, Ramsey BW; Early Pseudomonas Infection Control (EPIC) Investigators. Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis. Arch Pediatr Adolesc Med. 2011 Sep;165(9):847-56. doi: 10.1001/archpediatrics.2011.136.
PMID: 21893650RESULTSanders DB, Emerson J, Ren CL, Schechter MS, Gibson RL, Morgan W, Rosenfeld M; EPIC Study Group. Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in Young Children with Cystic Fibrosis. Ann Am Thorac Soc. 2015 Aug;12(8):1170-6. doi: 10.1513/AnnalsATS.201504-198OC.
PMID: 26288390DERIVEDMayer-Hamblett N, Kloster M, Rosenfeld M, Gibson RL, Retsch-Bogart GZ, Emerson J, Thompson V, Ramsey BW. Impact of Sustained Eradication of New Pseudomonas aeruginosa Infection on Long-term Outcomes in Cystic Fibrosis. Clin Infect Dis. 2015 Sep 1;61(5):707-15. doi: 10.1093/cid/civ377. Epub 2015 May 13.
PMID: 25972024DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bonnie Ramsey, MD
- Organization
- Seattle Childrens Hospital
Study Officials
- PRINCIPAL INVESTIGATOR
Bonnie W. Ramsey
University of Washington
- PRINCIPAL INVESTIGATOR
George Retsch-Bogart, MD
University of North Carolina, Chapel Hill
- PRINCIPAL INVESTIGATOR
Miriam Treggiari, MD
University of Washington
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Pediatrics
Study Record Dates
First Submitted
November 30, 2004
First Posted
December 1, 2004
Study Start
September 1, 2004
Primary Completion
June 1, 2009
Study Completion
August 1, 2009
Last Updated
February 28, 2014
Results First Posted
November 7, 2013
Record last verified: 2014-01