A new study found that the combination of inhaled dry powder mannitol with standard therapy for cystic fibrosis resulted in maintained improvement in lung function for 12 months. In addition to being effective and safe, the easy administration of the treatment might help enhance adherence with treatment in individuals suffering with the condition. The study, supported by Pharmaxis Limited, is published online ahead of print publication in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
The researchers enrolled 318 patients to participate in the double-blind study. Participants were then randomly assigned to receive either 400mg bid inhaled mannitol or 50 mg big inhaled mannitol (control group) for 26 weeks, followed by an additional 26 weeks of open-label active treatment. The researchers chose 50 mg dose for the control group as they believed it would not be clinically effective, based on a previous dose escalation investigation. Mannitol was given in addition to typical concomitant therapy, such as inhaled antibiotics and recombinant human deoxyribonuclease.
Lead researcher Moira L Aitken, MD, professor of pulmonary and critical care medicine at the University of Washington Medical Center, explained:
"Patients in the treatment group showed a 106.5 mL mean improvement in forced expiratory volume in one second (FEV1), an 8.22 percent improvement from baseline, compared with a 52.4 mL improvement (4.47 percent) in the control group. Forced vital capacity increased 136.3 mL in the treatment group, compared with 65.0 mL in the control group. Treated patients also experienced fewer pulmonary exacerbations than controls."
Between the treatment and control groups the difference in absolute FEV1 reached statistical significance (p=0.059), while the difference in relative change from baseline FEV1 reached significance (p=0.029). Participants in the treatment group maintained FEV1 improvements during the 26-week open-label phase of the investigation. From the start of the investigation to during the open-label phase, mean FEV1 improved 84.0 mL (6.3%) in the control group.
Both groups experienced comparable rates of side effects. During the study phase, qualitative sputum microbiology was performed for Staphylococcus aureus and Pseudomonas aeruginosa, due to potential influence of mannitol on lung microbiology. In both groups the researchers did not observe any qualitative changes in microbiology results from baseline.
In both groups compliance to treatment was good, 85.2% of participants in the treatment group and 88.7% of those in the control group using 60% or more of the medication dispensed.
According to the researchers the primary end point for the investigation, the difference in absolute FEV1 between groups, did not achieve significance. They explain that use of a single baseline visit to establish baseline FEV1 values may be the cause of this. When the team calculated baseline FEV1 values as an average of FEV1 values over two baseline visits, as in previous clinical intervention investigations, the overall increase in absolute FEV1 in the treatment group was considerably greater (p=0.0008). Furthermore, the 50 mg dose patients received in the control group may have had some benefit, which restricted the absolute difference between the two groups.
Dr. Aitken concluded:
"In our patients with cystic fibrosis, treatment with inhaled mannitol resulted in sustained improvements in lung function over 12 months, with a favorable safety profile.
In addition, the dry-powder inhaler used to administer mannitol is small, portable, easy to use and doesn't require thorough cleaning and disinfection after each use, which may help patients better adhere to treatment. Our results support the use of inhaled mannitol for the daily management of cystic fibrosis."
Written by Grace Rattue