Long term effects of denufosol tetrasodium in patients with cystic fibrosis
Felix Ratjen, Todd Durham, Tomas Navratil, Amy Schaberg, Frank J Accurso, Claire Wainwright, Matthew Barnes, Richard B Moss, TIGER-2 Study Investigator Group, Shawn Aaron, Richard Ahrens, Raouf Amin, Ran Anbar, Veena B Antony, Arthur Atlas, Scott Bell, Yves Berthiaume, Dorothy Bisberg, Phillip Black, Steven Boas, Anne Cairns, Hollis Chaney, Aaron S Chidekel, Bradley Chipps, James F Chmiel, John Paul Clancy, Barry Clements, Rubin Cohen, John Colombo, Paul Comber, Douglas Conrad, Peter Cooper, Maurice Cruz, Patrick Daigneault, Cori Daines, Joan DeCelie-Germana, Robin Deterding, Emily DiMango, Allen Dozor, Jordan Dunitz, Marie Egan, Cynthia Epstein, Robert Fink, Andreas Freitag, Deborah Froh, Magdalen Gondor, Gerald Gong, Gavin Graff, Hugh Greville, Karen Hardy, David Hicks, Robert Hopkins, Michelle Howenstine, James Hughes, Kimberly Jones, Palinder Kamra, Jamshed Kanga, Thomas Keens, John Kolbe, Nathan Kraynack, Chris Landon, Yolanda Lillquist, Theodore Liou, Brian Lyttle, Karen S McCoy, Kathleen T McKie, John McNamara, Bennie McWilliams, Keith Meyer, Roger Michael, Peter Middleton, Susan Millard, Kathryn Moffett, Mark Montgomery, Judith Morton, Richard Moss, Craig Nakamura, Samya Nasr, Christopher Oermann, Martin Phillips, Claude Prestidge, Adrienne Prestridge, Adupa Rao, Felix Ratjen, Clement Ren, George Retsch-Bogart, Santiago Reyes, Eduardo Riff, Maria Riva, Dion Roberts, Phil Robinson, Michael Rock, Mark Rolfe, Jonathan Rosen, Ronald Rubenstein, David Schaeffer, Michael Schechter, H Joel Schmidt, Peter Scott, Mitzi Scotten, Greg Shay, Terry Spencer, Elizabeth Tullis, Kristin Van Hook, Lori Vanscoy, Pierre Vauthy, Isabel Virella-Lowell, Judith Voynow, Claire Wainwright, Patricia Walker, Michael Wall, James Wallace, Peter Wark, Daniel Weiner, Pearce Wilcox, Robert W Wilmott, John Wilson, Robert Zanni, Pamela Zeitlin, Felix Ratjen, Todd Durham, Tomas Navratil, Amy Schaberg, Frank J Accurso, Claire Wainwright, Matthew Barnes, Richard B Moss, TIGER-2 Study Investigator Group, Shawn Aaron, Richard Ahrens, Raouf Amin, Ran Anbar, Veena B Antony, Arthur Atlas, Scott Bell, Yves Berthiaume, Dorothy Bisberg, Phillip Black, Steven Boas, Anne Cairns, Hollis Chaney, Aaron S Chidekel, Bradley Chipps, James F Chmiel, John Paul Clancy, Barry Clements, Rubin Cohen, John Colombo, Paul Comber, Douglas Conrad, Peter Cooper, Maurice Cruz, Patrick Daigneault, Cori Daines, Joan DeCelie-Germana, Robin Deterding, Emily DiMango, Allen Dozor, Jordan Dunitz, Marie Egan, Cynthia Epstein, Robert Fink, Andreas Freitag, Deborah Froh, Magdalen Gondor, Gerald Gong, Gavin Graff, Hugh Greville, Karen Hardy, David Hicks, Robert Hopkins, Michelle Howenstine, James Hughes, Kimberly Jones, Palinder Kamra, Jamshed Kanga, Thomas Keens, John Kolbe, Nathan Kraynack, Chris Landon, Yolanda Lillquist, Theodore Liou, Brian Lyttle, Karen S McCoy, Kathleen T McKie, John McNamara, Bennie McWilliams, Keith Meyer, Roger Michael, Peter Middleton, Susan Millard, Kathryn Moffett, Mark Montgomery, Judith Morton, Richard Moss, Craig Nakamura, Samya Nasr, Christopher Oermann, Martin Phillips, Claude Prestidge, Adrienne Prestridge, Adupa Rao, Felix Ratjen, Clement Ren, George Retsch-Bogart, Santiago Reyes, Eduardo Riff, Maria Riva, Dion Roberts, Phil Robinson, Michael Rock, Mark Rolfe, Jonathan Rosen, Ronald Rubenstein, David Schaeffer, Michael Schechter, H Joel Schmidt, Peter Scott, Mitzi Scotten, Greg Shay, Terry Spencer, Elizabeth Tullis, Kristin Van Hook, Lori Vanscoy, Pierre Vauthy, Isabel Virella-Lowell, Judith Voynow, Claire Wainwright, Patricia Walker, Michael Wall, James Wallace, Peter Wark, Daniel Weiner, Pearce Wilcox, Robert W Wilmott, John Wilson, Robert Zanni, Pamela Zeitlin
Abstract
Rationale: Denufosol stimulates chloride secretion independent of the chloride channel which is dysfunctional in cystic fibrosis (CF) and therefore has the potential to benefit CF patients regardless of genotype.
Objectives: To assess the efficacy of denufosol in CF patients with mild lung function impairment age 5 years and older.
Methods: This multicenter, randomized, parallel group double-blind placebo-controlled trial was conducted at 102 CF care centers in Australia, Canada and the United States (NCT00625612) The active group (n=233) received 60 mg denufosol via inhalation three times daily The primary efficacy endpoint was change in FEV(1) in liters from Day 0 to week 48.
Measurements and main results: 685 patients were screened for the study and 466 patients (233 in each group) were randomized to study treatment. The adjusted mean change in FEV(1)was 40 mL for denufosol and 32 mL for placebo with a resulting treatment effect of 8 mL (95% CI -0.040, 0.056). The average rate of change in FEV(1) percent of predicted over 0 to 48 weeks was -3.04% for placebo vs. -2.30 for denufosol (a difference of 24% relative to placebo) among all patients. The incidence of pulmonary exacerbation was 26% vs. 21% for the placebo and denufosol groups with no differences in the time to first event. The study treatments were well tolerated and there was no evidence of systemic effects in any safety parameter assessed.
Conclusions: In patients with CF treatment with denufosol for 48 weeks did not improve pulmonary function or reduce the incidence of pulmonary exacerbations.
Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Source: PubMed