Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study'
Miriam M Treggiari, Margaret Rosenfeld, Nicole Mayer-Hamblett, George Retsch-Bogart, Ronald L Gibson, Judy Williams, Julia Emerson, Richard A Kronmal, Bonnie W Ramsey, EPIC Study Group, Susan Banks-Schlegel, Gail Weinman, Robert J Beall, Preston W Campbell 3rd, Bruce C Marshall, Lynne Quittell, William Clarke, Mary Jane Kennedy, Robert Nelson, Kenneth N Oliver, Ronald Rubenstein, O Dale Williams, Gail Weinman, Susan Banks-Schlegel, Jungman Joo, Amanda Bailey, Molly Andrina, Amy Feldman, Robin Hill, Tamara Potter, Deborah Chambers, Shirley Desmon, Barbara Mathewson, David Escobar, Umer Khan, Kelli Joubran, Jane Burns, Jenny Stapp, Anne Marie Buccatt, Griffith Adam, Christopher Goss, Paul Comber, Magdalen Gondor, Blakeslee E Noyes, Karen McCoy, Ronald L Gibson, Margaret Rosenfeld, Frank Accurso, Jeffrey Wagener, Greg Omlor, Debbie Toder, David Orenstein, William M Gershan, Terry Spencer, Thomas Martin, David Waltz, John McNamara, Robert J Fink, Adrienne Prestridge, Philip Black, Maynard Dyson, H Worth Parker, Dennis Stokes, Aaron Chidekel, Michael Schecter, Lawrence McKean, Daniel Caplan, Peter Mogayzel, Robert A Schoumacher, Anne Marie Cairns, Allen Lapey, Henry L Dorkin, Margaret F Guill, Felice Adler-Shohet, Jay Lieberman, Robert L Zanni, David Schaeffer, Kathryn Blake, Allen Dozor, Nikhil Amin, Greg Shay, Albin Leong, Michael Wall, Gavin Graff, Michael W Konstan, Mary Ann Passero, Michelle Howenstine, Joan DeCelie-Germana, Susan Millard, Laurie Varlotta, Richard Moss, Ran D Anbar, Peter Hiatt, Scott H Davis, Hector H Gutierrez, Dennis Nielson, Terry Spencer, Richard C Ahrens, Jamshed F Kanga, Brian P O'Sullivan, Samya Nasr, Alicia DePaula, Fadel Ruiz, John L Colombo, L Francine Caffey, George Retsch-Bogart, Clement L Ren, Barbara A Chatfield, Deborah K Froh, Michael Rock, Elizabeth Perkett, Christopher Harris, Thomas Lahiri, Thomas Ferkol, Daniel Sheehan, Marlyn Woo, Miriam M Treggiari, Margaret Rosenfeld, Nicole Mayer-Hamblett, George Retsch-Bogart, Ronald L Gibson, Judy Williams, Julia Emerson, Richard A Kronmal, Bonnie W Ramsey, EPIC Study Group, Susan Banks-Schlegel, Gail Weinman, Robert J Beall, Preston W Campbell 3rd, Bruce C Marshall, Lynne Quittell, William Clarke, Mary Jane Kennedy, Robert Nelson, Kenneth N Oliver, Ronald Rubenstein, O Dale Williams, Gail Weinman, Susan Banks-Schlegel, Jungman Joo, Amanda Bailey, Molly Andrina, Amy Feldman, Robin Hill, Tamara Potter, Deborah Chambers, Shirley Desmon, Barbara Mathewson, David Escobar, Umer Khan, Kelli Joubran, Jane Burns, Jenny Stapp, Anne Marie Buccatt, Griffith Adam, Christopher Goss, Paul Comber, Magdalen Gondor, Blakeslee E Noyes, Karen McCoy, Ronald L Gibson, Margaret Rosenfeld, Frank Accurso, Jeffrey Wagener, Greg Omlor, Debbie Toder, David Orenstein, William M Gershan, Terry Spencer, Thomas Martin, David Waltz, John McNamara, Robert J Fink, Adrienne Prestridge, Philip Black, Maynard Dyson, H Worth Parker, Dennis Stokes, Aaron Chidekel, Michael Schecter, Lawrence McKean, Daniel Caplan, Peter Mogayzel, Robert A Schoumacher, Anne Marie Cairns, Allen Lapey, Henry L Dorkin, Margaret F Guill, Felice Adler-Shohet, Jay Lieberman, Robert L Zanni, David Schaeffer, Kathryn Blake, Allen Dozor, Nikhil Amin, Greg Shay, Albin Leong, Michael Wall, Gavin Graff, Michael W Konstan, Mary Ann Passero, Michelle Howenstine, Joan DeCelie-Germana, Susan Millard, Laurie Varlotta, Richard Moss, Ran D Anbar, Peter Hiatt, Scott H Davis, Hector H Gutierrez, Dennis Nielson, Terry Spencer, Richard C Ahrens, Jamshed F Kanga, Brian P O'Sullivan, Samya Nasr, Alicia DePaula, Fadel Ruiz, John L Colombo, L Francine Caffey, George Retsch-Bogart, Clement L Ren, Barbara A Chatfield, Deborah K Froh, Michael Rock, Elizabeth Perkett, Christopher Harris, Thomas Lahiri, Thomas Ferkol, Daniel Sheehan, Marlyn Woo
Abstract
Background: The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood.
Purpose: The present studies are designed to evaluate risk factors and outcomes associated with early Pa acquisition, and the benefits and harms of four anti-pseudomonal treatment regimens in young CF patients initiated after the first Pa positive respiratory culture.
Methods: The Early Pseudomonas Infection Control (EPIC) program consists of two studies, a randomized multicenter trial in CF patients ages 1-12 years at first isolation of Pa from a respiratory culture, and a longitudinal cohort study enrolling Pa-negative patients. Using a factorial design, trial participants are assigned for 18 months to either anti-pseudomonal treatment on a scheduled quarterly basis (cycled therapy) or based on recovery of Pa from quarterly respiratory cultures (culture-based therapy). The study drugs include inhaled tobramycin (300 mg BID) for 28 days, combined with either oral ciprofloxacin (15-20 mg/kg BID) or oral placebo for 14 days. The primary endpoints of the trial are the time to pulmonary exacerbation requiring IV antibiotics or hospitalization for respiratory symptoms, and the proportion of patients with new Pa-positive respiratory cultures during the study. The broad goals of the observational study are to describe the risk factors and outcomes associated with early acquisition of Pa. 306 patients were randomized in the clinical trial and 1787 were enrolled in the cohort study.
Conclusions: These companion studies will provide valuable epidemiological and microbiological information on early CF lung disease and Pa acquisition, and safety and clinical efficacy data on anti-pseudomonal treatment strategies for early Pa infections in the airways of young children with CF.
Trial registration: ClinicalTrials.gov NCT00097773 NCT00676169.
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Source: PubMed