Double-blind Placebo-controlled Multicenter Trial Research Articles

Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction.

Nimodipine is a 1,4-dihydropyridine derivative that shows a preferential cerebrovascular activity in experimental animals. Clinical data suggest that nimodipine has a beneficial effect on the neurologic outcome of patients suffering an acute ischemic stroke. Our double-blind placebo-controlled multicenter trial was designed to assess the effects of oral nimodipine on the mortality rate and neurologic outcome of patients with an acute ischemic stroke. One hundred sixty-four patients were randomly allocated to receive either nimodipine tablets (30 mg q.i.d.) or identical placebo tablets for 28 days. Treatment was always started less than or equal to 48 hours after the acute event. The Mathew Scale, slightly modified by Gelmers et al, was used for neurologic assessment. Mortality rate and neurologic outcome after 28 days were used as evaluation criteria. We considered 123 patients to be valid for the analysis of efficacy. Mortality rates did not differ significantly between groups. Neurologic outcome after 28 days of therapy did not differ between groups. However, when only those patients most likely to benefit from any intervention (Mathew Scale sum score of less than or equal to 65 at baseline) were analyzed separately in post hoc-defined subgroups, the nimodipine-treated subgroups showed a significantly better neurologic outcome. This result suggests that some patients with acute ischemic stroke will benefit from treatment with nimodipine tablets.

Antiarrhythmic Effects and Tolerability of Mexiletine in Patients with Suspected Acute Myocardial Infarction

The antiarrhythmic effects and tolerability of mexiletine 400mg administered intramuscularly to patients suspected of myocardial infarction before arrival at hospital, was evaluated in a randomised double-blind placebo-controlled multicentre trial. 99 patients received mexiletine, 97 placebo. In the mexiletine group, there was a slight, nonsignificant reduction in ‘significant arrhythmias’ [ventricular fibrillation, ventricular tachycardia or multifocal premature ventricular complexes (PVCs), or more than 10 PVCs/min] searched in continuous ECG recordings during patient transport. During the first 24 hours after admission to the coronary care unit, significantly more patients in the mexiletine group (28%) had signs of left ventricular failure than in the placebo group (15%). Mortality at 3 months was higher in the mexiletine group (20%) than in the placebo group (12.4%), but not significantly. Mexiletine serum concentrations on arrival at hospital and 3.5 hours after drug administration were in the commonly accepted therapeutic range. Intramuscular mexiletine 400mg does not appear suitable for the systematic prehospital prevention of ventricular arrhythmias in patients suspected of acute myocardial infarction.