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

Abstract

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 <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 <65 at baseline) were analyzed separately in post hoc-defined subgroups, the nimodipine-treated subgroup showed a significantly better neurologic outcome. This result suggests that some patients with acute ischemic stroke will benefit from treatment with nimodipine tablets.

A new model of temporary focal neocortical ischemia in the rat.

“…1 " 4 The other involves restoring cerebral blood flow (CBF) by using hemodilution 56 or fibrinolytic agents such as tissue plasminogen activator. 7 -10 With the expanded use of thrombolytic agents in clinical trials for stroke, animal models of temporary focal cerebral ischemia will assume added importance, not only to the study of reperfusion injury but also to the definition of ways in which this injury can be attenuated therapeutically.…”

Feasibility of Neuroprotective Agent Administration by Prehospital Personnel in an Urban Setting

“…These NAs have included N-methyl-D-aspartate antagonists, calcium channel blockers, sodium cell channel blockers, free-radical scavengers, and promoters of cell membrane repair. [15][16][17][18][19][20][21][22] Only 29 of the 178 studies limited patient enrollment to within 6 hours of symptom onset, and only 3 studies limited enrollment to Ͻ3 hours. The prolonged window of patient enrollment might be 1 reason why there have been such failures in so many clinical studies.…”

Untitled

“…Patients with low scores representing very severe deficit with a reduced level of consciousness, and patients with high scores representing minimal or localised deficit, are often excluded from further study because they are less likely to show a treatment effect. The results of drug studies can be readily compared when the same neurological scoring system is used: patients with a Mathew scale score of between 35 and 65 out of 100, indicating moderate deficit, showed a possible treatment benefit from nimodipine (Gelmers et al, 1988) and this was confirmed for patients with a Mathew score of less than 65 in a smaller study by Martinez-Vila et al (1990). However, numerous neurological scales are in use, such as the National Institutes of Health (NIH) motor scale, the Canadian Neurological Stroke Scale, and the Neurological or N-score, and diversity rather than conformity is the rule in stroke study.…”

“…For the purposes of drug treatment trials, the distribution and severity of stroke is often scored by more complex neurological examination scales (Brott et al, 1989a;Martinez-Vila et al, 1990;Paci et al, 1989;Trust Study Group, 1990). Patients with low scores representing very severe deficit with a reduced level of consciousness, and patients with high scores representing minimal or localised deficit, are often excluded from further study because they are less likely to show a treatment effect.…”