Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients.

BACKGROUND AND PURPOSE: The efficacy and safety of the neuroprotective drug clomethiazole was tested in a double blind placebo controlled trial in patients with a clinical diagnosis of acute hemispheric stroke. METHODS: Patients with symptom onset of /=60 points on the Barthel Index) at 90 days. RESULTS: A total of 1360 patients were included. In the main efficacy analysis (n=1353), 56.1% of patients taking clomethiazole and 54.8% of placebo patients reached relative functional independence. The difference was not statistically significant. An analysis of the effect of time since onset of symptoms showed no difference between the treatment groups. Clomethiazole was generally well tolerated and appeared safe in the population studied. Sedation was the most common adverse event, leading to treatment withdrawal that occurred in 15.6% of clomethiazole-treated patients compared with 4.2% of placebo-treated patients. In a subgroup classified before randomization as having total anterior circulation syndrome (TACS) (n=545, or 40% of all randomized patients), the percentage of those reaching relative functional independence was 40.8% on clomethiazole and 29.8% on placebo, a difference of approximately 11 percentage units. TACS patients have clinical symptoms suggesting a "large" stroke. CONCLUSIONS: Clomethiazole had no adverse or beneficial effect on long-term outcome for all patients but produced sedation. The hypothesis that clomethiazole is effective in patients with large strokes will be tested in a further study.

Enalapril in the long-term treatment of elderly hypertensives.

The long-term antihypertensive effects of enalapril were assessed for a period of up to 1 year in 44 elderly patients with mild-to-moderate essential hypertension. Following a 2-week placebo period, patients who were assigned to enalapril were followed for 6 weeks in a randomized clinical trial. In patients who benefited from enalapril, treatment was continued and subjects were followed for up to 1 year. Supine and standing systolic and diastolic blood pressures were significantly reduced throughout the 1-year period compared with baseline. The dosage of enalapril was increased from 10 to 20 mg daily in 12 patients; 8 required additional antihypertensive agents. Enalapril is effective in the long-term treatment of hypertension; no loss of antihypertensive agents. Enalapril is effective in the long-term treatment of hypertension; no loss of antihypertensive effect occurs.