YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy)

Abstract

T he goal of hyperacute stroke therapy is to recanalize the occlusive artery as soon as possible. Once a cerebral artery is occluded, blood and oxygen supply rapidly decrease and the neuron, glia cell, and vascular elements are immediately impaired, which leads to permanent damage.1 Early spontaneous recanalization occurs and rescues the brain tissue from ischemia, which is the underlying cause of most transient ischemic attacks. Over the past 2 decades, intravenous Background and Purpose-We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. Methods-The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). Results-One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (P=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (P=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P=0.738). thrombolysis using tissue-type plasminogen activator (tPA) therapy was the only established therapy and the first-line treatment to recanalize an occluded artery. 2 In addition, for the past 2 years, an increasing number of endovascular therapy (EVT) studies have introduced a new era in recanalization therapy. Conclusions-The3 However, there are still many patients who do not achieve recanalization. Thus, every therapy that can increase the rate of early recanalization is truly needed.A large number of neuroprotective agents have reduced ischemic damage in experimental studies. One of the most expected agents to improve the outcome of stroke patients was NXY-059. 4 However, it failed to show clinical benefit in its second trial. In Japan, edaravone, a free radical scavenger and neuroprotectant, was approved by the Japanese Ministry of Health, Labour and Welfare in 2001 for the treatment of ischemic stroke, within 24 hours of onset.5 Edaravone suppresses free ...

Anti-Inflammatory Targets for the Treatment of Reperfusion Injury in Stroke

“…This study showed that combination therapy accelerated recanalization and reduced the incidence of cerebral hemorrhage ( 214 ). The YAMATO study was then carried out to determine whether early (vs. late) edaravone infusion promoted early recanalization and reduced complications, but failed to show any difference in outcome with either paradigm ( 215 ).…”

tPA Helpers in the Treatment of Acute Ischemic Stroke: Are They Ready for Clinical Use?

“…Investigators in the Tissue-Type Plasminogen Activator and Edaravone Combination Therapy (YAMATO) study [60] attempted to assess whether edaravone administration before or during tPA therapy can expedite the recanalization of occluded arteries. This was a multicenter, prospective, randomized, and open-label study.…”

Perspective Treatment Goals for Brain Protection in Case of Acute Ischemia

“…Метою нейропротекторної терапії є подовження періоду терапевтичного вікна, що дозволяє розширити можливості для проведення тромболітичної терапії, зменшити розміри інфаркту мозку та захистити церебральну паренхіму від реперфузійного ушкодження [7].…”

“…У зв'язку із цим перспективним напрямом лікування ішемічного інсульту може вважатися застосування фармакологічних препаратів, здатних включитися в систему захисту мозку від окислювального стресу, запобігати вільнорадикальним процесам і забезпечувати антиоксидантну дію. Утім, попри очевидну доцільність антиоксидантної терапії в разі гіпоксії та ішемії мозку і наявність численних експериментальних доказів її ефективності, наразі зберігається дефіцит доступних для широкої клінічної практики антиоксидантних засобів, до того ж терміни і схеми їх застосування остаточно не визначені [3,[4][5][6][7].…”