纳美芬改善大面积脑梗死预后:随机对照前瞻性临床试验方案

Nalmefene improves prognosis in patients with a large cerebral infarction: study protocol for a randomized controlled prospective trial

背景:大脑中动脉主干梗死会造成大面积脑梗死,临床上常采用溶栓、降纤、血管扩张以及手术等方法进行治疗,但这些方法对患者预后的疗效存在争议。纳美芬是一种特异性吗啡受体阻断剂,具有神经保护作用。但是目前尚无其治疗大面积脑梗死有效性的临床研究。目的:以常规治疗为对照,观察纳美芬对大脑中动脉主干脑梗死患者的神经功能恢复作用。方法:随机对照前瞻性试验选取中国吉林大学第一医院收治的大脑中动脉主干梗死患者236例,随机分为对照组(n=116)和纳美芬组(n=120)。对照组采取常规治疗方法,纳美芬组在常规治疗基础上连续10 d静脉注射盐酸纳美芬注射液。试验以治疗结束后10 d时有效率作为主要评价指标。次要评价指标为:(1)治疗结束后10 d时的美国国立卫生院神经功能缺损评分;治疗前和治疗后10 d时的格拉斯哥昏迷评分;(3)治疗前和治疗5,10 d时对血清基质金属蛋白酶9水平;(4)治疗前和治疗10 d时头部行磁共振灌注成像检查结果。试验方案已在中国临床试验注册中心注册,注册号为Chi CTR-IOR-17013871。结果与结论:已完成的预试验结果显示,与对照组相比,治疗后纳美芬组患者美国国立卫生院神经功能缺损评分明显降低,治疗有效率增加,格拉斯哥昏迷评分明显升高,血清基质金属蛋白酶9水平下降,头部磁共振灌注病灶侧脑血流量和脑血容量明显增加,对比剂平均通过时间显著缩短。试验将为纳美芬联合常规治疗大面积脑梗死提供试验证据,为改善大面积脑梗死预后提供试验数据支持。

BACKGROUND:Occlusion of the middle cerebral artery trunk can cause large infarctions.Clinically,thrombolytic therapy,defibrillation,vasodilation,and surgery are often used to treat these large infarctions.However,the therapeutic efficacy of these therapeutic interventions in promoting prognosis remains controversial.Nalmefene,an opioid receptor antagonist,exhibits a neuroprotective effect.Few clinical studies are reported on the therapeutic efficacy of nalmefene in the treatment of large cerebral infarctions.OBJECTIVE:To investigate the therapeutic efficacy of nalmefene in restoring the neurologic function of patients with middle cerebral artery trunk infarction in comparison with conventional treatment as a control.METHODS:A total of236patients with middle cerebral artery trunk infarction who will receive treatment at the First Hospital of Jilin University,China will be randomly divided into a control group(n=116)and a nalmefene group(n=120).Patients in the control group will receive conventional treatment.Patients in the nalmefene group will receive10successive days of intravenous nalmefene hydrochloride injection based on conventional treatment.The primary outcome of this study is the effective rate at20days(10days after treatment).The secondary outcomes of this study include(1)the National Institutes of Health Stroke Scale(NIHSS)score at20days,used to evaluate neurologic function deficits;(2)Glasgow Coma Scale score at0(before treatment)and10days;(3)serum level of matrix metalloproteinase9at0,5and10days(before treatment and5and10days of treatment);(4)MRI perfusion imaging of the head at0and10days.This trial was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR-IOR-17013871).RESULTS AND CONCLUSION:Preliminary experiment results revealed that compared with the control group,NIHSS score was signficiantly decreased,effective rate was increased,Glasgow Coma Scale score was significantly increased,serum level of matrix metalloproteinase9was significantly decreased,cerebral blood flow and cerebral blood volume on the lesion side were signficiantly increased,and the mean transit time of contrast agent on the lesion side was significantly shortened in the nalmefene group.Findings from this study will provide clinical evidence for use of nalmefene in combination with conventional treatment for large cerebral infarctions and provide data support that this combined therapy can improve the prognosis in patients with large cerebral infarctions.