Outcomes of lower extremity arterial bypass using the Human Acellular Vessel in patients with chronic limb-threatening ischemia

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Bypass; Chronic-limb threatening ischemia; Peripheral arterial disease; Tissue-engineered vascular graft; Vascular prosthesis.