CAROTID OCCLUSION SURGERY STUDY

描述（由申请人提供）：PET测量的同侧氧提取分数（OEF）增加是症状性颈动脉闭塞患者随后卒中的一个强大的独立危险因素。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% Cl 1.6 - 33.4)，对应于OEF正常的42例患者的同侧卒中两年发生率为5.3%，OEF增加的39例患者的同侧卒中发生率为26.5% （p= 0.004）。在120天内出现半球症状的患者中，OEF正常的患者两年内同侧卒中发生率为12%，OEF增加的患者为40%。先前的PET研究表明，手术吻合颞浅动脉与大脑中动脉（STA-MCA）可以使OEF恢复正常。颈动脉闭塞手术研究（COSS）将验证STA-MCA手术吻合在最佳药物治疗的基础上可以减少40%的假设，尽管围手术期卒中和死亡，但最近（<120天）症状性颈内动脉闭塞和OEF增加的患者在两年内发生的同侧缺血性卒中（致命和非致命）。临床符合条件的单侧颈动脉闭塞患者通过任何血管成像证明，如果PET显示OEF增加，将被要求同意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也将寻求。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搭桥手术，然后进行医疗管理或单独进行医疗管理。所有随机患者将每隔三个月随访两年。手术组的主要终点是以下指标的组合：(1)术后30天（手术组）或随机化后（非手术组）所有卒中和死亡的发生情况；(2)随机化后两年内同侧缺血性卒中的发生情况。调整预期的2年死亡率，372例患者（每组186例）将提供90%的能力来检测预期的差异（40%对24.2%）。91人被随机分配。假设25-30%的PET扫描显示OEF增加，这将需要招募1400名临床合格的受试者进行PET检查。本建议涵盖该试验的第二个5年。

DESCRIPTION (provided by applicant): 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.