The optimal time window for the use and dosage of nimodipine for acute massive cerebral infarction: study protocol for a randomized controlled trial

Background: A neuroprotective effect of nimodipine on acute cerebral infarction has been confirmed, but there are few reports regarding the therapeutic effect of nimodipine on acute massive cerebral infarction. There is also no consensus on the optimal time window for the use and dosage of nimodipine. This trial is planned to answer these questions using a double-blind randomized controlled design.Methods/Design: This is a double-blind randomized controlled trial. The experiments will be conducted in the Department of Neurology, Central Hospital Affiliated to Shenyang Medical College of China. One hundred patients with acute massive cerebral infarction will be randomly assigned to a control group and a treatment group. Patients in the control and treatment groups will receive intravenous infusion of citicoline and intravenous infusion of nimodipine (10 mg/d) respectively, for 7 consecutive days. Simultaneously, to determine the appropriate time window for treatment with nimodipine, patients in the treatment group will be divided into four subgroups according to the time of nimodipine administration: < 3 hours, 3–6 hours, 6–24 hours, and > 24 hours. The main outcome measures are: the National Institutes of Health Stroke Scale and the Rankin scale will be used to assess the severity and recovery of neurological impairment, respectively. Cranial computed tomography and magnetic resonance imaging will be used to evaluate brain lesions and the Barthel index will be used to assess the activities of daily living. Secondary outcome measures are heart rate and blood pressure.Discussion: It is hoped that the experimental results can determine the best application time window and dosage of nimodipine for acute massive cerebral infarction.Trial registration: ClinicalTrials.gov identifier: NCT02248233; registered on 22 September 2014.

背景：尼莫地平（nimodipine）对急性脑梗死的神经保护作用已得到证实，但关于其对急性大面积脑梗死的治疗效果的报道甚少，且尼莫地平的最佳使用时机窗与给药剂量尚未达成共识。本试验拟采用双盲随机对照设计，旨在解答上述问题。

## 方法/研究设计
本研究为双盲随机对照试验，试验将在中国沈阳医学院附属中心医院神经内科开展。将100例急性大面积脑梗死患者随机分配至对照组与治疗组：对照组患者接受胞磷胆碱静脉输注，治疗组患者接受尼莫地平（10 mg/d）静脉输注，两组均连续给药7天。同时，为明确尼莫地平治疗的适宜时机窗，治疗组患者将根据尼莫地平给药时间分为四个亚组：<3小时、3~6小时、6~24小时及>24小时。
主要结局指标包括：采用美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale）评估神经功能缺损严重程度，采用Rankin量表评估神经功能恢复情况；采用头颅计算机断层扫描与磁共振成像评估脑部病变情况，采用巴氏指数（Barthel index）评估日常生活活动能力。次要结局指标为心率与血压。

## 讨论
本研究期望通过试验结果明确尼莫地平治疗急性大面积脑梗死的最佳应用时机窗与给药剂量。

## 试验注册
ClinicalTrials.gov 注册编号：NCT02248233；注册日期：2014年9月22日。