Hypothermia

在公认的神经保护策略中，低温一直被认为是最有效的。 了解缺血和再灌注的最新见解表明，低温可能是延长卒中治疗时间窗的理想方式。虽然冷却患者的困难限制了这种潜在有效疗法的测试，但最近的技术发展使我们能够对超过3小时的患者进行血管内冷却的I期临床试验。本研究的目的是确认血管内冷却器械的性能，并确定更大规模临床研究的参数， 例如样本大小和衡量指标。还将在这一有限的患者人群中评估低温治疗联合溶栓治疗卒中的初步有效性。为此，我们将实现两个具体目标： 1)描述在卒中后3至6小时内开始降温的卒中患者中低温的安全性特征。大量临床前数据支持有效低温的窗口可能长于3小时的假设。我们将确定冷却装置的安全性，并收集结局数据，用于估计较大的II期试验的样本量。 2)确定卒中发作后3至6小时内溶栓和低温联合使用的安全性。溶栓试验未能证明卒中发作后3小时后治疗的患者获益。然而，在每项试验中，都有获益的趋势，荟萃分析表明，在后期治疗的患者中有积极的，但效果很小。我们推测低温结合溶栓治疗对这类患者可能有效。我们将确定有创血管内冷却导管联合溶栓的安全性。我们将收集安全性和结局数据，以帮助设计更大规模的对照II期试验。

Among putative neuroprotection strategies, hypothermia has long been recognized as the most potent. Recent insights in understanding ischemia and reperfusion suggest that hypothermia may be an ideal modality for extending the stroke therapy time window. Although difficulties cooling patients limited testing of this potentially effective therapy, recent developments in technology allow us to mount a Phase 1 clinical trial of intravascular cooling for patients presenting beyond 3 hours. The purpose of this study is to confirm the performance of an endovascular cooling device and to establish the parameters for a larger clinical study, such as sample size and indices of measurement. Preliminary effectiveness of hypothermia treatment in combination with thrombolysis for stroke will also be evaluated in this limited patient population. To do this, we will address 2 specific aims: 1) Characterize the safety profile of hypothermia in stroke patients who initiate cooling between 3 and 6 hours after stroke. Substantial pre-clinical data supports the hypothesis that the window for effective hypothermia may be longer that 3 hours. We will establish safety of the cooling device, and collect outcome data to be used for estimating sample size in larger, Phase 2 trials. 2) Establish the safety of thrombolysis and hypothermia used together between 3 to 6 hours after stroke onset. Thrombolysis trials failed to demonstrate benefit to patients treated later that 3 hours following stroke onset. In each trial, however, there was a trend toward benefit, and meta-analyses suggest that there is a positive, but small effect in later treated patients. We hypothesize that hypothermia, combined with thrombolysis, may prove effective in such patients. We will establish the safety of invasive, endovascular-cooling catheter in combination with thrombolysis. We will collect safety and outcomes data to aid in the design of larger, controlled Phase 2 trial.