Dose-ranging study of riluzole in amyotrophic lateral sclerosis

摘要: Abstract Summary Background Amyotrophic lateral sclerosis (ALS) is a progressive disease with no effective treatment. In an initial study, riluzole decreased mortality and slowed muscle-strength deterioration in ALS patients. We have carried out double-blind, placebo-controlled, multicentre study to confirm those findings assess drug efficacy at different doses. Methods 959 patients clinically probable or definite of less than 5 years' duration were randomly assigned treatment placebo 50 mg, 100 200 mg daily; randomisation was stratified by centre site onset (bulbar limb). The primary outcome survival without tracheostomy. Secondary outcomes rates change functional measures (muscle strength, status, respiratory function, patient's assessments fasciculation, cramps, stiffness, tiredness). analysis the comparison dose intention-to-treat. Drug-effect on assessed before (log-rank test) after adjustment for known prognostic factors (Cox's model). Findings At end median follow-up 18 months, 122 (50·4%) placebo-treated 134 (56·8%) who received mg/day alive tracheostomy (unadjusted risk 0·79, p0·076; adjusted 0·65, p=0·002). groups receiving daily, 131 (55·3%) 141 (57·8%) (relative 0·76, p=0·04; 0·61, p=0·0004). There significant inverse response death. No scale discriminated between groups. most common adverse reactions asthenia, dizziness, gastrointestinal disorders, rises liver enzyme activities; they commonest dose. Interpretation Overall, safety results suggest that has best benefit-to-risk ratio. This confirms well tolerated lengthens ALS.