摘要
目的 在本协作组第一阶段研究基础上,通过改变降纤酶治疗剂量和时限,缩短治疗时间窗,探讨不同治疗方案下降纤酶治疗急性脑梗死的有效性及安全性。方法 多中心、随机、双盲、安慰剂对照研究。卒中症状发生在 12h以内的急性脑梗死患者被随机分配至分别接受降纤酶或安慰剂两个治疗组。降纤酶首剂量 15U,以后隔日 5U,共 4次,均加入生理盐水 250ml中,静脉滴注。安慰剂组静脉滴注生理盐水 250ml。主要有效终点是 3个月时的良好功能状态 (Barthel指数≥95 )及明显依赖生存状态(Barthel指数≤60);安全性终点为出血事件及病死率;次要评价指标包括发病14d时神经功能缺损评分及 1年时的卒中复发率。结果 自 2001年 9月至 2003年 7月在全国 46个中心共入选 1053例患者,降纤酶组和安慰剂组完成治疗全过程的比例相近 [ 80 5% ( 424 /527 )与86 9% (457 /526) ]。降纤酶组 3个月时达良好功能状态的比例明显高于安慰剂组 [ 52 2% ( 212 /406)与 42 8% (190 /443),P=0 007],明显依赖生存患者比例略低于安慰剂组 [27 7% (112 /406)与32 4% (143 /443),P=0 136]。6h以内开始治疗的患者中,达良好功能状态患者的比例两组间差异有统计学意义(P=0 001),明显依赖生存患者比例两组间差异也有统计学意义(P=0 022)。降纤酶组
Objective To evaluate the efficacy and safety of defibrase under different treatment protocol by changing dose, shortening therapeutic time window and increasing duration of treatment based on the first stage study of the Cooperative Group for Reassessment of Defibrase.Methods A multicenter, randomized, double-blind, placebo-controlled study was carried out. The patients with acute cerebral infarction within 12 hours of stroke onset were randomly allocated to receive either an initial intravenous infusion of defibrase 15 U or placebo 250 ml of normal saline, subsequent infusion 5 U or placebo were given on the 3rd, 5th, 7th, 9th day respectively. This treatment protocol was determined on two pretrials bases of 68 patients in 11 centers. The primary efficacy end points were functional status including favorable functional status (Barthel Index≥95) and obvious dependent survival status (Barthel Index≤60) at 3 months. The safety variables were bleeding events and mortality. The secondary efficacy end points included Chinese Stroke Neurological Functional Deficits Scale score at 14 days and recurrence rate of stroke at 1 year.Results Totally 1053 patients were enrolled at 46 centers from September 2001 to July 2003, and 527 patients were randomly assigned to receive defibrase and 526 to receive placebo. A similar proportion of patients in both groups completed a full course of treatment (80.5%(424/527) vs 86.9%(457/526)). There were a significantly greater proportion of favorable functional outcomes in defibrase treated patients than in placebo group at 3 months (52.2%(216/406) vs 42.8%(190/443),P=0.007), and the proportion of obvious dependent survival status was a little lower in defibrase group as compared with placebo group (27.7%(112/406) vs 32.4%(143/443),P=0.136). Much greater proportion of favorable functional outcomes were achieved in defibrase treated patients than in placebo group (63.5%(122/193) vs 45.7%(94/206),P=0.001) at 3 months in patients who were treated within 6 h of stroke onset, and there was also a significant difference in the proportion of obvious dependent survival patients between two groups (19.8%(38/193) vs 29.8%(61/206),P=0.022). The neurological functional deficits had more improvement in the defibrase group than in the placebo group at 14 days ( P=0.014), recurrence rate of stroke at 1 year was lower in the defibrase group comparing with placebo group (6.2%(23/369) vs 10.1%(40/397), P=0.053). There was a tendency to increase symptomatic intracranial hemorrhage (12 vs 8 patients, P=0.282) and risk to increase significantly extracranial bleeding events(20 vs 7 patients, P=0.006). A higher proportion of patients with intra- and extra- cranial hemorrhage in defibrase treated patients was seen in the patients with fibrinogen level<1.30 g/L than in those with fibrinogen≥1.30 g/L (10.6%(26/252) vs 3.8%(6/162)). The patients of death at 3 months were slightly more in the defibrase group than in the placebo group (7.3%(31/424) vs 4.8%(22/457),P=0.119).Conclusion The defibrase was effective to improve neurological function and ability of daily living for acute cerebral infarction within 12 h of symptoms onset. The effect was much better for acute cerebral infarction within 6 h of symptoms onset. There was a risk to increase intra- and extra-cranial hemorrhage during defibrase administration. The occurrence of bleeding events should be related to the plasma fibrinogen level.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2005年第1期11-16,共6页
Chinese Journal of Neurology
