Original Article
Pooled analysis of two large randomised phase III inhaled mannitol studies in cystic fibrosis,☆☆

https://doi.org/10.1016/j.jcf.2012.11.002Get rights and content
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Abstract

Background

To evaluate safety and efficacy of inhaled mannitol treatment in subgroups of a large global CF population.

Methods

Data were pooled from two multicentre, double-blind, randomised, controlled, parallel group phase III studies in which 600 patients inhaled either mannitol (400 mg) or control (mannitol 50 mg) twice a day for 26 weeks.

Results

Both the mean absolute change in FEV1 (mL) and relative change in FEV1 by % predicted from baseline for mannitol (400 mg) versus control were statistically significant (73.42 mL, 3.56%, both p < 0.001). Increases in FEV1 were observed irrespective of rhDNase use. Significant improvements in FEV1 occurred in adults but not children (6–11) or adolescents (aged 12–17). Pulmonary exacerbation incidence was reduced by 29% (p = 0.039) in the mannitol (400 mg) group.

Conclusions

Sustained six-month improvements in lung function and decreased pulmonary exacerbation incidence indicate that inhaled mannitol is an important additional drug in the treatment of CF.

Abbreviations

AE
adverse event
ASL
airway surface liquid
BID
twice a day
BMI
body mass index
CF
cystic fibrosis
CFTR
CF transmembrane conductance regulator
CI
confidence interval
DPI
dry powder inhaler
FEV1
forced expiratory volume in 1 second
FVC
forced vital capacity
GRAS
generally recognised as safe
HS
hypertonic saline
ITT
intent to treat
MCC
mucociliary clearance
MedDRA
medical dictionary for regulatory activities
MMRM
Mixed-effects model for repeated measures
MTT
mannitol tolerance test
PA
Pseudomonas aeruginosa
PDPE
protocol defined pulmonary exacerbation
PE
pulmonary exacerbation
SAE
serious adverse event
SD
standard deviation

Keywords

Cystic fibrosis
Mannitol dry powder
FEV1
Airway mucociliary clearance
Clinical study
Dry powder inhalers

Cited by (0)

This work was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London and the Cystic Fibrosis Foundation (CFF) and Therapeutic Development Network (TDN).

☆☆

Clinical trials registered with www.clinicaltrials.gov (NCT00446680, CF301 and NCT00630812, CF302).