Cervene (Nalmefene) in acute ischemic stroke : final results of a phase III efficacy study. The Cervene Stroke Study Investigators

BACKGROUND AND PURPOSE: The goals of the present study were to assess the efficacy and safety of nalmefene (Cervene) in patients with acute (< or =6 hours) ischemic stroke and to investigate the safety of combined recombinant tissue plasminogen activator and nalmefene in a separate subset of patients. Nalmefene, an opioid antagonist with relative kappa receptor selectivity, has shown neuroprotective effects in multiple experimental central nervous system injury and ischemic models. Results from an earlier phase II study in patients with acute ischemic stroke suggested that nalmefene was safe and tolerable and may be effective for patients <70 years old. METHODS: This investigation was a phase III, placebo-controlled, double-blind, randomized study of a 24-hour infusion of nalmefene. Patients with acute ischemic stroke who had an onset of symptoms within 6 hours and a baseline score of > or =4 on the NIH Stroke Scale were randomized to receive either 60 mg nalmefene administered as a 10-mg bolus over 15 minutes and then a 50-mg infusion over 23.75 hours or placebo. The primary efficacy outcome was the proportion of patients achieving a score of > or =60 on the Barthel Index and a rating of "moderate disability" or better on the Glasgow Outcome Scale at 12 weeks. Assessments were performed at baseline (predose), hours 12 and 24, days 2 and 7, and week 12. RESULTS: A total of 368 patients were randomized at 42 centers, including 32 patients treated with recombinant tissue plasminogen activator and study drug. Nalmefene was well tolerated. Overall, there was no significant difference in 3-month functional outcome for nalmefene treatment compared with placebo on any of the planned analyses. A prospective secondary analysis also failed to find a treatment effect in patients <70 years old. CONCLUSIONS: Although nalmefene appears to be safe and well tolerated, this study failed to find any treatment benefit in stroke patients treated within 6 hours.     

Treatment of acute ischemic stroke. Open trial with continuous intravenous heparinization

To determine safety of early anticoagulation in patients with acute ischemic stroke, 150 consecutive patients were treated with continuous intravenous heparinization for one to 17 days (median, seven days) in an open trial. Fourteen patients had transient ischemic attacks and 136 patients had acute cerebral infarctions (Cls). None of the patients with transient ischemic attacks experienced untoward events. Of those with acute Cl, four patients (3%) suffered a new, or extension of, Cl; six patients (4.4%) suffered hemorrhagic complications, four patients (3%) died during treatment, and six patients (4%) died afterwards. Three of the deaths were related to treatment complications. Only 13 patients (8.6%) experienced fluctuation of deficit. Median hospitalization was 25.5 days. Recovery of function was good to excellent in 81% of the patients with acute Cl; 75% of the survivors were ambulatory, and about 66% of the patients had either a mild or a minimal neurologic deficit at discharge. The incidence of untoward events in patients with acute Cl was high enough (7.4%) for us to conclude that the efficacy of continuous intravenous heparinization in acute ischemic stroke should be established with controlled studies before its routine use can be recommended.     

The Clomethiazole Acute Stroke Study in hemorrhagic stroke (Class-H): Final results

Background and Purpose: Clomethiazole (CMZ) is a neuroprotectant that may improve outcome in patients with acute major strokes. In a previous study that included 94 hemorrhagic stroke patients (CLASS), a mortality reduction and functional outcome favorable to CMZ was seen. We sought to establish the safety of CMZ in acute hemorrhagic stroke patients and to determine whether a trial of medical therapy for cerebral hemorrhage was feasible. Methods: The safety of CMZ (n = 96) versus a placebo (n = 102) in hemorrhagic stroke patients was evaluated in a randomized, double-blind trial. Treatment began after a computed tomography (CT) scan confirmed the presence of hemorrhage and within 12 hours from symptom onset. Patients received 68 mg/kg of CMZ intravenously over 24 hours. Safety was assessed by collecting serious adverse events (SAE), including deaths up to 90 days after treatment. Functional and neurologic outcome were also monitored. Results: Hemorrhage volumes were found to be similar between groups (26 ± 56 mL CMZ v 26 ± 35 mL placebo). Sedation was reported as an adverse event during therapy in 55% of the CMZ patients versus 13% of the placebo patients. The number of SAE reports was 53 in the CMZ group and 46 in the placebo group. Differences on functional outcome measures were minor. Death within 90 days occurred in 19 CMZ patients versus 11 placebo patients (Odds Ratio [OR] 2.04; 95% confidence interval [CI] 0.92, 4.55; P = .08). After adjusting for baseline covariate imbalances, the mortality difference was less apparent (OR 1.82; 95% CI 0.69, 4.81; P = .23). Conclusions: The feasibility of performing neuroprotectant trials for acute cerebral hemorrhage patients has been established, but requires careful balancing of important predictive indicators, including baseline severity, hematoma location, presence of intraventricular blood, and possibly, coumadin use. The clinical experience to date has identified no specific major safety concerns with the use of CMZ in acute hemorrhagic stroke patients. Additional clinical trials will be required to confirm safety and establish the efficacy of CMZ in acute hemorrhagic stroke patients.     

GM1 ganglioside therapy in acute ischemic stroke. Italian Acute Stroke Study--Hemodilution + Drug

Eleven of 31 clinical centers participating in the Italian Acute Stroke Study--Hemodilution carried out a preliminary study on the effectiveness of ganglioside GM1 in acute stroke; 502 patients were randomized to GM1 (GM1, n = 121), GM1 plus hemodilution (GM1 + H, n = 128), placebo (P, n = 130), or placebo plus hemodilution (P + H, n = 123) groups less than or equal to 12 hours after onset of a hemispheric cerebral infarct. The patients were treated for 15 days and were evaluated on Days 21 and 120 after the onset of stroke. Intention-to-treat analysis failed to show any differences in neurologic deficit, mortality, or neurologic disability among the groups. Efficacy analysis showed a significantly higher degree of neurologic improvement in GM1 group patients compared with patients in the P group during the first 15 days. GM1-treated patients (GM1 and GM1 + H groups) showed a significantly higher degree of neurologic improvement during the first 10 days compared with the placebo-treated patients (P and P + H groups). These differences were no longer statistically significant at Day 120. Our results provide a rationale for the planning of a larger, multicenter trial of GM1 ganglioside in acute stroke.     

急性脑梗死早期OCSP分型研究☆

目的验证OCSP(OxfordshireCommunityStrokeProject)分型法在急性脑梗死临床中的使用价值.方法回顾分析我院近2年202例急性脑梗塞早期OCSP分型情况及影像学特征.结果OCSP分型与影像学结果有良好对应关系;我院急性脑梗死的亚型构成脑隙性脑梗塞占65.3%,部分前循环梗塞19.3%,完全前循环梗塞9.9%,后循环梗塞5.4%.结论OCSP法可用于急性脑梗死的早期分型、指导治疗、评估预后;我国急性脑梗死的亚型构成中轻型病例多,重型少.     

Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial

BACKGROUND: A multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of fasudil, a Rho-kinase inhibitor (RKI), in the treatment of acute ischemic stroke. METHODS: A total of 160 patients, who were able to receive drug treatment within 48 h of acute ischemic stroke onset were enrolled. Patients received either 60 mg fasudil or a placebo (saline) by intravenous injection over 60 min, twice daily for 14 days. The primary end points were neurological status at 2 weeks after the start of treatment, and clinical outcome at 1 month after the onset of symptoms. RESULTS: Fasudil treatment resulted in significantly greater improvements in both neurological functions (p=0.0013), and clinical outcome (p=0.0015). There were no serious adverse events reported in the fasudil group. The average trough value (12 h values) of active metabolite hydroxyfasudil, another RKI, in healthy elderly volunteers receiving 60 mg of fasudil was 0.077 microM-a concentration well above that needed to inhibit Rho-kinase (0.025-0.05 microM). CONCLUSION: Treatment with fasudil within 48 h of acute ischemic stroke onset significantly improved the patient's clinical outcome. This study found fasudil to be a useful and safe drug for patients with acute ischemic stroke. Further evaluations, for example, 3-month functional outcomes in a larger clinical trial, may help to define the efficacy of fasudil in acute ischemic stroke.