ISC 2015：TNK-tPA溶栓治疗轻型卒中的合适剂量（TEMPO-1研究）

国际卒中大会(ISC2015)公布的TEMPO-1研究表明，在伴有颅内动脉闭塞的轻型卒中患者中，利用替奈普酶(TNK-tPA)溶栓具有较好的安全性和可行性，并且0.25 mg/kg剂量实现的再通率较高。

此项多中心、前瞻性队列研究共纳入50例CTA显示颅内动脉闭塞的卒中患者，并分别给予TNK-tPA 0.1和0.25 mg/kg治疗。主要转归为症状性颅内(SICH)和颅外出血发生率。次要转归包括90天时完全性神经病学(NIHSS 0～1)和功能(mRS 0～1)恢复、4～8小时CTA显示再通以及少量出血。

结果显示，受试者中位基线NIHSS为2，中位年龄为71岁。颅内闭塞的血管分别为大脑中动脉M1段(MCA-M1，13);MCA-M2 (21); MCA-M3 (8);大脑后动脉P1段(PCA-P1 ，1), PCA-P2 (1);分支、椎动脉/PICA (3) 和不确定的 (3)。

在0.1 mg/kg组患者中，用药4～8小时后完全再通者为21.7%，部分再通者为26.1%，无再通者为52.2%。而在0.25 mg/kg组中，相应的比率分别为56.6%、13%和30.4%。0.25 mg/kg TNK-tPA治疗组有1例(2%)患者发生SICH。

90天致残和神经病学转归评估结果于大会时公布。

摘要：

Abstract 160: Final Results of the Thrombolysis for Minor Ischemic Stroke With Proven Acute Symptomatic Occlusion Using TNK-tPA (TEMPO-1) Trial

Abstract

Background: Minor stroke and TIA with an intracranial occlusion are associated with a 20-30% risk of neurological deterioration and subsequent disability. TNK-tPA compared to alteplase is easier to administer, has a longer half-life, higher fibrin specificity and possibly a lower rate of intracranial hemorrhage. Therefore, it may be an ideal thrombolytic agent for recanalization in this population.

Methods: TEMPO-1 was a multi-centre, prospective cohort, TNK-tPA dose-escalation, safety and feasibility trial. Patients with an NIHSS < 6, intracranial arterial occlusion on CTA, with no sign of well-evolved infarction who were treated within a 12h treatment window were enrolled. 50 patients were enrolled. The first 25 patients were treated at a dose of 0.1 mg/kg, and a second cohort of 25 patients treated at a dose of 0.25 mg/kg. Primary outcome was the rate of symptomatic intracranial (SICH) and extracranial hemorrhage. SICH was defined as a new ICH with ≥ 2 points worsening on the NIHSS. SITS-MOST definition of SICH was also assessed. Secondary outcomes include complete neurological (NIHSS 0-1) and functional (mRS 0-1) recovery at 90 days, recanalization at 4-8 h on CTA and minor bleeding.

Results: Median baseline NIHSS was 2 (SD 1.24) and median age was 71 years (SD 18). Site of intracranial occlusions were: MCA-M1 (13), MCA-M2 (21), MCA-M3 (8), PCA-P1 (1), PCA-P2 (1) branches, vertebral artery/PICA (3) and undetermined (3). There was one SICH seen [2% (1/50), CI95 0.5%-10.6%], which was in the 0.25mg/Kg dose tier. There were no SICH by the SITS-MOST definition. For the 0.1mg/Kg dose tier recanalization between 4-8 hours post drug was complete in 21.7%, partial in 26.1% and no recanalization was seen in 52.2%. For the 0.25mg/Kg dose tier recanalization between 4-8 hours post drug was complete in 56.6%, partial in 13% and no recanalization was seen in 30.4%. 90-day disability and neurological outcome assessment will be available at the time of the International Stroke Conference.

Conclusion: We have shown the safety and feasibility of thrombolysis with TNK-tPA in a minor stroke with intracranial occlusion population. Rates of recanalization are high in the 0.25mg/Kg tier and we have chosen this dose to proceed with a randomized controlled trial in this population.