CAROTID OCCLUSION SURGERY STUDY

PET测量的同侧氧摄取分数（OEF）增加是症状性颈动脉闭塞患者随后发生卒中的一个强有力的独立危险因素。圣路易斯颈动脉闭塞研究发现，OEF增加对同侧缺血性卒中的相对风险为7.3（95% CI 1.6 - 33.4），对应于42例OEF正常患者和39例OEF增加患者的同侧卒中两年发生率分别为5.3%和26.5%（p= 0.004）。在120天内出现半球症状的患者中，OEF正常的患者两年同侧卒中发生率为12%，OEF增加的患者为40%。既往PET研究表明，颞浅动脉与大脑中动脉（STA-MCA）的手术吻合可使OEF恢复正常。颈动脉闭塞手术研究（COSS）将检验以下假设：在最近（<120天）有症状的颈内动脉闭塞和OEF增加的患者中，将STA-MCA手术吻合术添加到最佳药物治疗中，可以减少40%的术后同侧缺血性卒中（致死性和非致死性），尽管有围手术期卒中和死亡。如果PET显示OEF增加，则将要求通过任何血管成像证实单侧颈动脉闭塞的临床合格患者同意接受PET和治疗随机化。如有必要，同意进行补充动脉造影，以确认闭塞或证明颅外和颅内血管。同意并符合动脉造影和PET标准的患者将以1：1的比例随机接受STA-MCA旁路手术，然后进行药物管理或仅进行药物管理。所有随机化患者将每隔3个月随访2年。手术组的主要终点是以下各项的组合：（1）术后30天（手术组）或随机化后30天（非手术组）所有卒中和死亡的发生率和（2）随机化后2年内同侧缺血性卒中的发生率。调整预期2年死亡率后，372例患者（每组186例）将提供90%的把握度来检测预期差异（40% vs. 24.2%）。91人已随机分组。假设25-30%的PET扫描将显示OEF增加，这将需要共招募1400例临床合格受试者进行PET。本提案涵盖本试验的第二个5年。

Ipsilateral increased oxygen extraction fraction (OEF) measured by PET is a powerful independent risk factor for subsequent stroke in patients with symptomatic carotid occlusion. The St. Louis Carotid Occlusion Study found that the relative risk conferred by increases OEF was 7.3 (95% Cl 1.6 - 33.4) for ipsilateral ischemic stroke corresponding to two year rates for ipsilateral stroke of 5.3% in 42 patients with normal OEF and 26.5% in 39 patients with increased OEF (p=.004). In patients with hemispheric symptoms within 120 days, the two year ipsilateral stroke rates were 12% in patients with normal OEF and 40% in patients with increased OEF. Previous PET studies have demonstrated that surgical anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA) can restore OEF to normal. The Carotid Occlusion Surgery Study (COSS) will test the hypothesis that STA-MCA surgical anastomosis when added to best medical therapy can reduce by 40%, despite perioperative stroke and death, subsequent ipsilateral ischemic stroke (fatal and non-fatal) at two years in patients with recent (<120 days) symptomatic internal carotid artery occlusion and increased OEF. Clinically eligible patients with unilateral carotid artery occlusion demonstrated by any vascular imaging will be asked to consent to PET and treatment randomization if PET shows increased OEF. If necessary, consent for a supplemental arteriogram to confirm occlusion or demonstrate that extracranial and intracranial vessels will be sought as well. Those who agree and meet both arteriographic and PET criteria will be randomized 1:1 to undergo STA-MCA bypass surgery followed by medical management or medical management alone. All randomized patients will be followed at three month intervals for two years. The primary endpoint in the surgical group is the combination of the following: (1) 30 day post-operative (surgical group) or post-randomization (non-surgical group) occurrence of all stroke and death and (2) the occurrence of ipsilateral ischemic stroke within two years of randomization. Adjusting for anticipated 2 year mortality, 372 patients (186 in each group) will provide 90% power to detect the anticipated difference (40% vs. 24.2%). 91 have been randomized. Assuming 25-30% of PET scans will demonstrate increased OEF, this will require enrolling a total of 1400 clinically eligible subjects for PET. This proposal covers the second 5 years of this trial.