Division of Vascular and Endovascular Surgery, Mayo Clinic, Rochester, MN.
Division of Vascular and Endovascular Surgery, Mayo Clinic, Rochester, MN.
J Vasc Surg. 2024 Feb;79(2):348-357.e2. doi: 10.1016/j.jvs.2023.10.040. Epub 2023 Oct 26.
Patients with chronic limb-threatening ischemia (CLTI) and no great saphenous vein to use as a conduit for arterial bypass have a high risk for amputation despite advances in medical and endovascular therapies. This report presents findings from a U.S. Food and Drug Administration (FDA) supported study of the Human Acellular Vessel (HAV) (Humacyte Inc.) used as a conduit for arterial bypass in patients with CLTI and inadequate or absent autologous conduit.
The HAV is a 6-mm, 40-cm vessel created from human vascular smooth muscle cells seeded onto a polyglycolic acid scaffold pulsed in a bioreactor for 8 weeks as cells proliferate and the scaffold dissolves. The resultant vessel is decellularized, creating a nonimmunogenic conduit composed of collagen, elastin, and extracellular matrix. The FDA issued an Investigational New Drug for an intermediate-sized, single-center study of the HAV under the agency's Expanded Access Program in patients with advanced CLTI and inadequate or absent autologous conduit. Technical results and clinical outcomes were analyzed and reported.
Between March 2021 and July 2023, 29 patients (20 males; mean age, 71 ± 11 years) underwent limb salvage operation using the HAV as a bypass conduit. Most patients had advanced CLTI (Rutherford class 5/6 in 72%; wound, ischemia, and foot infection stage 3/4 in 83%), and 97% had previously failed revascularization(s) of the extremity. Two HAVs were sewn together to attain the needed bypass length in 24 patients (83%). Bypasses were to tibial arteries in 23 patients (79%) and to the popliteal artery in 6 (21%). Technical success was 100%, and the 30-day mortality rate was 7% (2 patients). With 100% follow-up (median, 9.3 months), the limb salvage rate was 86% (25/29 patients). There were 16 reinterventions to restore secondary patency, of which 15 (94%) were successful. Primary and secondary patency of the HAV at 9 months were 59% and 71%, respectively.
The HAV has demonstrated short- to intermediate-term safety and efficacy as an arterial bypass conduit in a complex cohort of patients with limb-threatening ischemia and no autologous options. This experience using the FDA's Expanded Access Program provides real-world data to inform regulatory deliberations and future trials of the HAV, including the study of the vessel as a first-line bypass conduit in less severe cases of chronic limb ischemia.
尽管在医学和血管内治疗方面取得了进步，但患有慢性肢体威胁性缺血（CLTI）且没有大隐静脉可用于动脉旁路的患者，其截肢风险仍然很高。本报告介绍了美国食品和药物管理局（FDA）支持的一项研究结果，该研究使用 Human Acellular Vessel（HAV）（Humacyte Inc.）作为 CLTI 患者和自体导管不足或不存在的动脉旁路的导管。
HAV 是一种 6 毫米、40 厘米长的血管，由接种在生物反应器中的人血管平滑肌细胞制成，细胞在生物反应器中增殖 8 周，支架溶解。由此产生的血管去细胞化，形成由胶原蛋白、弹性蛋白和细胞外基质组成的非免疫原性导管。FDA 根据该机构的扩大准入计划，为 HAV 的一项中等规模、单中心研究发放了研究性新药，该研究纳入了晚期 CLTI 患者和自体导管不足或不存在的患者。分析并报告了技术结果和临床结局。
2021 年 3 月至 2023 年 7 月，29 名患者（20 名男性；平均年龄 71±11 岁）接受了使用 HAV 作为旁路移植物的肢体挽救手术。大多数患者患有晚期 CLTI（72%为 Rutherford 5/6 级；83%为创面、缺血和足部感染 3/4 期），97%的患者此前曾进行过肢体血运重建。24 名患者（83%）将 2 个 HAV 缝合在一起以获得所需的旁路长度。旁路至胫骨动脉 23 例（79%），至腘动脉 6 例（21%）。技术成功率为 100%，30 天死亡率为 7%（2 例）。在 100%的随访（中位随访时间 9.3 个月）中，肢体挽救率为 86%（29 例患者中的 25 例）。有 16 次再介入以恢复次要通畅性，其中 15 次（94%）成功。HAV 的初始和次要通畅率分别为 59%和 71%。
在没有自体选择的肢体威胁性缺血和复杂患者队列中，HAV 作为动脉旁路移植物具有短期至中期的安全性和有效性。本研究使用 FDA 的扩大准入计划提供了真实世界的数据，为 HAV 的监管审议和未来试验提供了信息，包括在慢性肢体缺血程度较轻的情况下将该血管作为一线旁路移植物的研究。
