Long-term inhaled dry powder mannitol in cystic fibrosis: an international
randomized study.
Author(s): Aitken ML, Bellon G, De Boeck K, Flume PA, Fox HG, Geller DE, Haarman EG,
Hebestreit HU, Lapey A, Schou IM, Zuckerman JB, Charlton B; CF302 Investigators.
Collaborators: Alais ME, Bonina AJ, Ditondo JC, Lentini E, Marques I, Pinero R,
Segal E, Teper A, Lyttle B, Michael R, Rabin H, Casimir G, DeBoeck C, Deseger K,
Malfroot A, Bellon G, Bremont F, David V, Dubus JC, Durieu I, Foucaud P, Kessler
R, Leroy S, Marguet C, Munck A, Turck D, Weiss L, Fischer R, Hebestreit H,
Nahrlich L, Reithmuller J, Haarman E, Merkus P, Aitken M, Barnett B, Borowitz D,
Daines C, Dovey M, Flume P, Fornos P, Froh D, Geller D, Jain M, Jones K, Konig P,
Lapey A, Lapin C, McWilliams B, Meyer K, Murphy P, Oermann C, Royall J, Rulon E,
Salathe M, Schaeffer D, Schoumacher R, Wallace J, Willey-Courand DB, Williams R,
Zeitlin P, Zuckerman J.
Affiliation(s): University of Washington Medical Center, Seattle, WA 98195-6522, USA.
moira@u.washington.edu
Publication date & source: 2012, Am J Respir Crit Care Med. , 185(6):645-52
RATIONALE: New treatment strategies are needed to improve airway clearance and
reduce the morbidity and the time burden associated with cystic fibrosis (CF).
OBJECTIVES: To determine whether long-term treatment with inhaled mannitol, an
osmotic agent, improves lung function and morbidity.
METHODS: Double-blind, randomized, controlled trial of inhaled mannitol, 400 mg
twice a day (n = 192, "treated" group) or 50 mg twice a day (n = 126, "control"
group) for 26 weeks, followed by 26 weeks of open-label treatment.
MEASUREMENTS AND MAIN RESULTS: The primary endpoint was absolute change in FEV(1)
from baseline in treated versus control groups, averaged over the study period.
Secondary endpoints included other spirometric measurements, pulmonary
exacerbations, and hospitalization. Clinical, microbiologic, and laboratory
safety were assessed. The treated group had a mean improvement in FEV(1) of 105
ml (8.2% above baseline). The treated group had a relative improvement in FEV(1)
of 3.75% (P = 0.029) versus the control group. Adverse events and sputum
microbiology were similar in both treatment groups. Exacerbation rates were low,
but there were fewer in the treated group (hazard ratio, 0.74; 95% confidence
interval, 0.42-1.32; P = 0.31), although this was not statistically significant.
In the 26-week open-label extension study, FEV(1) was maintained in the original
treated group, and improved in the original control group to the same degree.
CONCLUSIONS: Inhaled mannitol, 400 mg twice a day, resulted in improved lung
function over 26 weeks, which was sustained after an additional 26 weeks of
treatment. The safety profile was also acceptable, demonstrating the potential
role for this chronic therapy for CF. Clinical trial registered with
www.clinicaltrials.gov (NCT 00630812).
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