Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study

Abstract

This international phase III study of inhaled dry powder mannitol was a randomised, double-blind, 26-week study, followed by a further 26-week, open-label (OL) extension. 324 cystic fibrosis (CF) patients were randomised, in a 3:2 ratio, to mannitol (400 mg b.i.d.) and control groups. The primary efficacy end-point was to determine the change in forced expiratory volume in 1 s (FEV1) over the double-blind phase. Secondary end-points included changes in forced vital capacity and pulmonary exacerbations.A significant improvement in FEV1 was seen over 26 weeks (p,0.001) and was apparent by 6 weeks, irrespective of concomitant recombinant human deoxyribonuclease (rhDNase) use. At 26 weeks, there was a significant improvement in FEV1 of 92.9 mL for subjects receiving mannitol compared with controls (change from baseline 118.9 mL (6.5%) versus 26.0 mL (2.4%); p,0.001). Improvements in FEV1 were maintained up to 52 weeks in the OL part of the study. There was a 35.4% reduction in the incidence of having an exacerbation on mannitol (p50.045).The incidence of adverse events (AEs) was similar in both groups, although treatment-related AEs were higher in the mannitol compared with the control group. The most common mannitolrelated AEs were cough, haemoptysis and pharyngolaryngeal pain.Mannitol showed sustained, clinically meaningful benefit in airway function in CF, irrespective of concomitant rhDNase use. Mannitol appears to have an acceptable safety profile for patients with CF.

Tiotropium Respimat® in cystic fibrosis: Phase 3 and Pooled phase 2/3 randomized trials

“…However, in the phase 3 trial, patients ≤11years in the placebo group showed an improvement in percent-predicted FEV 1 AUC 0-4h over time, which suggests a learning effect during the trial among the younger patients, who were less skilled in performing spirometry. In a recent study of inhaled mannitol, a sustained, significant (p<0.001) improvement in FEV 1 was seen in the control group [12], but the improvement was not significant in another similarly designed study (p=0.059) in similar populations [13]. Interestingly, in the pooled analysis, significant improvements in the mannitol versus control group in FEV 1 occurred in patients aged ≥18 years old but not in younger participants [14].…”

Growth on mannitol-rich media elicits a genome-wide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner

“…However, the precise role played by EPS during infection of the CF lung remains unclear, and direct evidence for EPS production by BCC within the lung is currently lacking. The fact that mannitol promotes EPS biosynthesis has also gained further clinical relevance following the approval of a dry-powder preparation of mannitol for use as an inhaled osmolyte in CF patients (Jaques et al, 2008;Daviskas et al, 2010;Teper et al, 2011;Bilton et al, 2011). Since colonization with BCC was amongst the exclusion criteria for participation in the mannitol powder clinical trials, the impact of this osmolyte therapy on the course of infection in Burkholderia-infected patients has yet to be determined.…”

Quality of life in Hungarian patients with cystic fibrosis

“…A CF súlyosságának megítélésére az 1958-ben publikált, még napjainkban is egyszerűen és hitelesen alkalmazható pontrendszert használtuk [19]. Az összpont-szám négy fő területből adódik: általános aktivitás, fi zikális vizsgálat, tápláltsági állapot és radiológiai lelet.…”