TY - JOUR
T1 - Long-Term Inhaled Dry Powder Mannitol in Cystic Fibrosis An International Randomized Study
AU - Aitken, Moira L.
AU - Bellon, Gabriel
AU - de Boeck, Kris
AU - Flume, Patrick A.
AU - Fox, Howard G.
AU - Geller, David E.
AU - Haarman, Eric G.
AU - Hebestreit, Helge U.
AU - Lapey, Allen
AU - Schou, I. Manjula
AU - Zuckerman, Jonathan B.
AU - Charlton, Brett
PY - 2012
Y1 - 2012
N2 - 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 FEV1 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 FEV1 of 105 ml (8.2% above baseline). The treated group had a relative improvement in FEV1 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, FEV1 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)
AB - 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 FEV1 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 FEV1 of 105 ml (8.2% above baseline). The treated group had a relative improvement in FEV1 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, FEV1 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)
U2 - https://doi.org/10.1164/rccm.201109-1666OC
DO - https://doi.org/10.1164/rccm.201109-1666OC
M3 - Article
C2 - 22198974
SN - 1073-449X
VL - 185
SP - 645
EP - 652
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 6
ER -