Accepted for Publication: April 8, 2011.
Author Contributions: Dr Treggiari had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Treggiari, Mayer-Hamblett, Kulich, Kronmal, Williams, Gibson, Burns, Rosenfeld, and Ramsey. Acquisition of data: Retsch-Bogart, Mayer-Hamblett, Hiatt, Gibson, Spencer, Orenstein, Chatfield, Froh, and Burns. Analysis and interpretation of data: Treggiari, Retsch-Bogart, Mayer-Hamblett, Khan, Kronmal, and Ramsey. Drafting of the manuscript: Treggiari, Retsch-Bogart, Mayer-Hamblett, Khan, Kronmal, Hiatt, Burns, and Ramsey. Critical revision of the manuscript for important intellectual content: Treggiari, Retsch-Bogart, Mayer-Hamblett, Kulich, Kronmal, Gibson, Spencer, Orenstein, Chatfield, Froh, Burns, Rosenfeld, and Ramsey. Statistical analysis: Mayer-Hamblett, Khan, Kulich, and Kronmal. Obtained funding: Treggiari, Mayer-Hamblett, Kronmal, and Ramsey. Administrative, technical, and material support: Retsch-Bogart, Hiatt, Gibson, Spencer, and Burns. Study supervision: Retsch-Bogart, Mayer-Hamblett, Williams, Hiatt, Gibson, Froh, and Ramsey.
Financial Disclosure: Study drugs and devices were supplied free of charge by Novartis Pharmaceutical Corp (TIS) and Bayer Healthcare AG (oral ciprofloxacin and oral placebo); compressors and nebulizers were provided by PARI Respiratory Equipment Inc. Dr Chatfield has had research grants or contracts from Gilead Pharmaceuticals, Vertex Pharmaceuticals, and the Cystic Fibrosis Foundation.
Funding/Support: The research for this article was supported in part by Cystic Fibrosis Foundation grant EPIC0K0, National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases grant U01-HL080310, and National Center for Research Resources grants ULI-RR025014-03, 1UL1-RR025744, 1UL1-RR025780, UL1-RR025005, UL1-RR0024979, UL1RR025747, UL1-RR025011, 1UL-RR024975, and M01-RR02172.
Role of the Sponsor: The industry sponsors had no role in the analysis, interpretation, and writing of the manuscript. The National Heart, Lung, and Blood Institute–appointed Data and Safety Monitoring Board played a role in the conduct, collection, management, analysis, and interpretation of the data and reviewed and approved the final manuscript.
This article is featured in the Archives Journal Club. Go here to download teaching PowerPoint slides.
Additional Contributions: Special thanks to families of children with CF who participated in the study and whose dedication to research made the trial possible. Patricia Roush, AuD, provided guidance and consultation on audiometric testing. She received financial compensation for her work.
EPIC Participating Centers and Investigators
CYSTIC FIBROSIS FOUNDATION THERAPEUTICS
Robert J. Beall, Preston W. Campbell III, Bruce C. Marshall.
CYSTIC FIBROSIS SERVICES
Wayne Gabbert, Daniel Klein, Kevin Smith, Jim Stone.
CYSTIC FIBROSIS SERVICES PHARMACY
Erica Crilly, Kwei Leong.
DATA AND SAFETY MONITORING BOARD
Lynne Quittell (chair), Columbia University; William R. Clarke, University of Iowa; Mary Jane Kennedy, Virginia Commonwealth University; Kenneth N. Olivier, National Institute of Allergy and Infectious Disease; Ronald C. Rubenstein, Children's Hospital of Philadelphia; O. Dale Williams, University of Alabama at Birmingham; Gail G. Weinmann, executive secretary, National Heart, Lung, and Blood Institute; Susan Banks-Schlegel, National Heart, Lung, and Blood Institute.
George Retsch-Bogart (chair), University of North Carolina at Chapel Hill; Susan Banks-Schlegel, National Heart, Lung, and Blood Institute; Robert J. Beall, Cystic Fibrosis Foundation; Preston W. Campbell, Cystic Fibrosis Foundation; Ron L. Gibson, University of Washington; Gavin R. Graff, The Penn State Milton S. Hershey Medical Center; Hector H. Gutierrez, The University of Alabama at Birmingham; Jamshed Kanga, University of Kentucky; Richard Kronmal, University of Washington; Robert Kuhn (ad hoc), University of Kentucky; Thomas Lahiri, Vermont Children's Hospital at Fletcher Allen Health Care; Nicole Mayer-Hamblett, University of Washington; Catherine McKeon, National Institute of Diabetes and Digestive and Kidney Diseases; Wayne Morgan, University of Arizona; Blakeslee E. Noyes, Saint Louis University/Cardinal Glennon Children's Medical Center; Bonnie W. Ramsey, University of Washington; Margaret Rosenfeld, University of Washington; Lisa Saiman (ad hoc), Columbia University Medical Center; Michael S. Schechter, Emory University; Dennis C. Stokes, Dartmouth-Hitchcock Medical Center; Jeffrey S. Wagener, The Children's Hospital; Judy Williams, CFFT Therapeutics Development Network Coordinating Center.
CRA/study monitors: Clare Castro, Deborah Chambers, Amy Feldman, Robin Hill, Tamara Potter, Sarah Velde; study managers: Shirley Desmon, Amanda Nelson, Judy Williams; clinical trials unit manager: Barbra Fogarty; data management: Barbara Mathewson, Trudi White; statisticians: Umer Khan, Steve Knutzen, Nicole Mayer-Hamblett; study pharmacist: Morty Cohen; quality assurance: Cheryl Kruesel, Dolores Seefried, Anna Wharton; network development: Natalie Beauchene, Lisya Van Housen; regulatory: Lynne Larson; finance: Donna Crist, Chris Fitzpatrick, Sherryl Singleton; microbiology core lab: Anne Marie Buccat, Jane Burns; medical monitors: Christopher Goss.
PARTICIPATING SITES (SITE INVESTIGATORS AND RESEARCH COORDINATORS)
Akron Children's Hospital/Children's Hospital Medical Center of Akron, Akron, Ohio: site investigators (SI): Nathan C. Kraynack, Gregory Omlor, Kimberly A. Spoonhower; research coordinators (RC): Deborah A. Ouellette; Albany Medical College, Albany, New York: SI: Paul G. Comber; RC: Julie Pursel; Alfred I. duPont Hospital for Children, Wilmington, Delaware: SI: Aaron Chidekel; RC: Sandra M. Budd; All Children's Hospital, St. Petersburg, Florida: SI: Magdalen Gondor; RC: Stasia Lehmann; Children's Hospital Boston, Boston, Massachusetts: SI: Lindo Terry Spencer; RC: Erin Leone Thakkallapalli; Children's Hospital Los Angeles, Los Angeles, California: SI: Arnold C. G. Platzker; Children's Hospital of Michigan Wayne State University, Detroit: SI: Ibrahim Abdulhamid; RC: Catherine Van Wagnen; Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania: SI: David Orenstein; RC: Judy Fulton, Sandy Hurban; Children's Hospital of Wisconsin/Medical College of Wisconsin, Milwaukee: SI: William Gershan; RC: Tami Miller; Children's Hospitals and Clinics of Minnesota, Minneapolis: SI: Michael Pryor; RC: Sandy Landvik, Mary Sachs; Children's Memorial Medical Center, Chicago, Illinois: SI: Adrienne Prestridge; Children's Mercy Hospital, Kansas City, Missouri: SI: Philip Black; RC: Lora Bear; Cook Children's Health Care System, Fort Worth, Texas: SI: Maynard C. Dyson, Karen D. Schultz; RC: Sara Scott; Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire: SI: H. Worth Parker; Emory University, Atlanta, Georgia: SI: Michael S. Schechter; RC: Jeannette Peabody; Helen DeVos Children's Hospital, Grand Rapids, Michigan: SI: Susan L. Millard, John N. Schuen; RC: Teri L. Crumb, Tom Symington; Indiana University/Riley Hospital for Children, Indianapolis: SI: Michelle Howenstine; RC: Terry Barclay; Kaiser Permanente Medical Center, Oakland, California: SI: Greg Shay; RC: Julie Lee; Lucile Packard Children's Hospital/Stanford University, Palo Alto, California: SI: Richard Moss; RC: Colleen Dunn, Zoe Davies; Maine Medical Center, Portland: SI: Anne Marie Cairns, Thomas Mellow; RC: Mary Ellen Corrigan; Massachusetts General Hospital, Boston: SI: Allen Lapey; Medical College of Georgia, Augusta: SI: Margaret F. Guill, Katie McKie; Memorial Miller Children's Hospital, Long Beach, California: SI: Felice Adler-Shohet; RC: Nan O'Donnell; Monmouth Medical Center, Long Branch, New Jersey: SI: Robert L. Zanni; RC: Bridget Marra; Nationwide Children's Hospital, Columbus, Ohio: SI: Karen S. McCoy; Nemours Children's Clinic, Jacksonville, Florida: SI: David A. Schaeffer; RC: Donna L. Pingel, Rena A. Sprinkle; New York Medical College, Valhalla: SI: Nikhil Amin, Allen J. Dozor; RC: Ingrid Gherson; Oregon Health Sciences University, Portland: SI: Michael Wall; Rainbow Babies and Children's Hospital, Cleveland, Ohio: SI: Michael Konstan; RC: Colette Bucur, Cheryl Velotta; Seattle Children’s, Seattle, Washington: SI: Ronald L. Gibson, Margaret Rosenfeld; RC: Sharon McNamara; St. Christopher's Hospital for Children, Philadelphia, Pennsylvania: SI: Laurie Varlotta; St Louis University/Cardinal Glennon Children's Medical Center, St Louis: SI: Blakeslee E. Noyes; RC: Vikki L. Kociela; Schneider Children's Hospital, New Hyde Park, New York: SI: Joan DeCelie-Germana; RC: Lynn Bonitz; SUNY Upstate Medical University, Syracuse, New York: SI: Ran D. Anbar; RC: Donna M. Linder, Valoree N. Suttmore; Texas Children's Hospital, Houston: SI: Peter W. Hiatt; RC: Charlene Hallmark; The Children's Hospital, Denver, Colorado: SI: Frank J. Accurso, Jeffrey S. Wagener; RC: Shelley A. Mann; The Children's Medical Center of Dayton/Wright State University, Dayton, Ohio: SI: Robert J. Fink, Gary A. Mueller; RC: Sandy R. Bartosik; The Johns Hopkins Medical Institutions, Baltimore, Maryland: SI: Peter J. Mogayzel Jr, Pamela L. Zeitlin; RC: Karen A. Callahan, Carolyn G. Chapman; The PennState Milton S. Hershey Medical Center, Hershey, Pennsylvania: SI: Gavin R. Graff, Michael S. Schwartz; RC: Lisa M. Allwein, Diane M. Kitch; The University of Alabama at Birmingham, Birmingham: SI: Hector H. Gutierrez; RC: Lacrecia Britton, Gina Sabbatini; University of California, San Francisco: SI: Dennis W. Nielson; RC: Diem Tran; University of Iowa, Iowa City: RC: Jean Frauenholtz, Mary Teresi; University of Kentucky College of Medicine, Lexington: SI: Michael I. Anstead, Jamshed F. Kanga; RC: Catherine Dudderar; University of Massachusetts Memorial Health Care, Worcester: SI: Brian P. O’Sullivan; RC: Dawn Baker; University of Michigan, Ann Arbor: SI: Samya Z. Nasr; University of Mississippi Medical Center, Jackson: SI: Kim Adcock; University of Nebraska Medical Center, Omaha: SI: John Colombo; RC: Dee Acquazzino; University of North Carolina at Chapel Hill: SI: George Retsch-Bogart; RC: Carol Barlow, Diane Towle; University of Rochester Medical Center, Rochester, New York: SI: Clement L. Ren; University of Tennessee Health Science Center, Memphis: SI: Robert A. Schoumacher; RC: Barbara A. Culbreath, M. Teresa Knight; University of Utah, Salt Lake City: SI: Barbara Chatfield; RC: Susan Griffiths; University of Virginia, Charlottesville: SI: Deborah K. Froh; RC: Robin Kelly; University of Wisconsin–Madison: SI: Michael J. Rock; RC: Linda Makholm; Vanderbilt Children's Hospital, Nashville, Tennessee: SI: Elizabeth Perkett; RC: Alice Bray; Vermont Children's Hospital at Fletcher Allen Health Care, Burlington: SI: Thomas Lahiri; RC: Sandra Diehl.