French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group

Abstract

The effect of amiloride, a sodium channel blocker, has been evaluated in a multicenter randomized double-blind placebo-controlled trial in cystic fibrosis patients more than 5-years-old (n = 137) whose forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and forced mid-expiratory flow (FEF(25-75)) were not below 50%, 50%, and 30% of reference values, respectively. Patients were randomly allocated to two parallel groups. Sixty-four patients were chronically colonized with Pseudomonas aeruginosa; they received either amiloride or placebo as a nebulized solution three times daily for 6 months. Routine treatments were continued. Patients chronically colonized with Pseudomonas received nebulized colimycine twice a day for a month during the third and sixth months of treatment. Bronchopulmonary exacerbations were treated in the usual way. The effects of the amiloride treatment were assessed at the end of the 6-month treatment period. The effects on FVC and secondarily on FEV(1), FEF(25-75), the number of days on antibiotic therapy, the Shwachman score, a nutritional index (weight/height(2)), the change in sputum bacterial flora, and nocturnal cough were assessed. For the patients not chronically colonized with Pseudomonas, the effect of the treatment was also evaluated by counting chronic colonizations with pathogens appearing during the trial period. The present study failed to demonstrate any significant benefit of amiloride over placebo on FVC, FEV(1), and the other secondary endpoints in the studied population. Neither the chronically colonized, nor the noncolonized patients benefited. The confidence intervals of the differences between treatment groups indicated small differences that were most likely of no clinical significance. Complementary analyses taking into account the gender, the type of mutation, the subpopulations whose FVC and FEV(1) were below 80% of normal values at the beginning of the study, and also patients less than 10 years old, did not show any statistically or clinically significant improvements following amiloride therapy.