ALSRT 2001Low.

Methods	Amyotrophic Lateral Sclerosis riluzole‐tocopherol study (ALSRT). Randomised, double‐blind, placebo‐controlled trial with parallel group design (two intervention groups).
Participants	Country: France. Number of participants randomised: 288, 158 men and 130 women, mean age 64 years. Inclusion criteria: probable or definitive amyotrophic lateral sclerosis (ALS), according to El Escorial criteria, over 18 years of age at recruitment, to be able to fully understand the study information, have been treated with riluzole 950 mg b.i.d. for at least three months without presenting side effects. Exclusion criteria: signs of dementia and/or major psychiatric disorders, another concomitant serious disease, or handicap likely to interfere with their assessment of survival, forced vital capacity of less than 60%, monoclonal gammopathy, conduction blocks of motor nerves on electromyography, hepatic or renal disfunction, pregnancy or breast feeding, creatinine plasma concentration above 200 µM, alanine aminotransferase and/or aspartate transaminase activity greater than twice the upper limit of the normal range, known hepatic disease, taking drugs known to be hepatotoxic, enzyme‐inducing or enzyme‐inhibiting, taking vitamin E.
Interventions	Participants were randomly assigned to receive: group 1: vitamin E 500 mg plus riluzole 50 mg (n = 144); group 2: placebo (n = 144) plus riluzole 50 mg; one capsule (vitamin E) and one tablet (Riluzole) daily for one year.
Outcomes	The primary outcome measure was: change in functional status of each patient using the modified Norris limb scale. The secondary outcome measures were: survival (defined as the time to death or tracheostomy), bulbar function assessed with the Norris bulbar scale (total possible score 39) and manual muscle testing.
Notes	Compliance with treatment was checked by measuring the plasma vitamin E levels. Compliance with treatment good. In the vitamin E group, a highly significant increase in plasma levels of vitamin E was observed after 3 months of treatment. No losses to follow‐up. One hundred and forty‐six patients (74 in the placebo group and 72 in the alpha‐tocopherol group) did not complete the one‐year treatment period. Study agents were supplied by: alpha‐tocopherol (Toco 500R) Laboratories Rhone‐Poulenc Rorer (now trading under the name Laboratories Aventis); riluzole Rhone‐Poulenc Rorer. Additional information received through personal communication with the authors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Sequence generation was achieved using computer random number generation.
Allocation concealment (selection bias)	Low risk	Allocation was controlled by a central and independent randomisation unit, so that intervention allocations could not have been foreseen in advance of, or during, enrolment.
Blinding (performance bias and detection bias) All outcomes	Low risk	The trial was described as blinded, the parties that were blinded, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The numbers and reasons for dropouts and withdrawals in all intervention groups were described.
Selective reporting (reporting bias)	Low risk	Pre‐defined, or clinically relevant and reasonably expected outcomes are reported on.
Other bias	Low risk	The trial appears to be free of other components that could put it at risk of bias.