Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass
Objective: The human acellular vessel (HAV) was evaluated for surgical bypass in a phase II study. The primary results at 24 months after implantation have been reported, and the patients will be evaluated for ≤10 years. Methods: In the present report, we have described the 6-year results of a prosp...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | JVS - Vascular Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666350322000803 |
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| author | Piotr Gutowski, MD, PhD Malgorzata Guziewicz, MD, PhD Marek Ilzecki, MD, PhD Arkadiusz Kazimierczak, MD, PhD Jeffrey H. Lawson, MD, PhD Heather L. Prichard, PhD Stanislaw Przywara, MD, PhD Rabih Samad, MD, PhD William Tente, MS Jakub Turek, MD Wojcieh Witkiewicz, MD, PhD Norbert Zapotoczny, MD Tomaz Zubilewicz, MD, PhD Laura E. Niklason, MD, PhD |
| author_facet | Piotr Gutowski, MD, PhD Malgorzata Guziewicz, MD, PhD Marek Ilzecki, MD, PhD Arkadiusz Kazimierczak, MD, PhD Jeffrey H. Lawson, MD, PhD Heather L. Prichard, PhD Stanislaw Przywara, MD, PhD Rabih Samad, MD, PhD William Tente, MS Jakub Turek, MD Wojcieh Witkiewicz, MD, PhD Norbert Zapotoczny, MD Tomaz Zubilewicz, MD, PhD Laura E. Niklason, MD, PhD |
| author_sort | Piotr Gutowski, MD, PhD |
| collection | DOAJ |
| description | Objective: The human acellular vessel (HAV) was evaluated for surgical bypass in a phase II study. The primary results at 24 months after implantation have been reported, and the patients will be evaluated for ≤10 years. Methods: In the present report, we have described the 6-year results of a prospective, open-label, single-treatment arm, multicenter study. Patients with advanced peripheral artery disease (PAD) requiring above-the-knee femoropopliteal bypass surgery without available autologous graft options had undergone implantation with the HAV, a bioengineered human tissue replacement blood vessel. The patients who completed the 24-month primary portion of the study will be evaluated for ≤10 years after implantation. The present mid-term analysis was performed at the 6-year milestone (72 months) for patients followed up for 24 to 72 months. Results: HAVs were implanted in 20 patients at three sites in Poland. Seven patients had discontinued the study before completing the 2-year portion of the study: four after graft occlusion had occurred and three who had died of causes deemed unrelated to the conduit, with the HAV reported as functional at their last visit. The primary results at 24 months showed primary, primary assisted, and secondary patency rates of 58%, 58%, and 74%, respectively. One vessel had developed a pseudoaneurysm deemed possibly iatrogenic; no other signs of structural failure were reported. No rejections or infections of the HAV occurred, and no patient had required amputation of the implanted limb. Of the 20 patients, 13 had completed the primary portion of the study; however, 1 patient had died shortly after 24 months. Of the remaining 12 patients, 3 died of causes unrelated to the HAV. One patient had required thrombectomy twice, with secondary patency achieved. No other interventions were recorded between 24 and 72 months. At 72 months, five patients had a patent HAV, including four patients with primary patency. For the entire study population from day 1 to month 72, the overall primary, primary assisted, and secondary patency rate estimated using Kaplan-Meier analysis was 44%, 45%, and 60% respectively, with censoring for death. No patient had experienced rejection or infection of the HAV, and no patient had required amputation of the implanted limb. Conclusions: The infection-resistant, off-the-shelf HAV could provide a durable alternative conduit in the arterial circuit setting to restore the lower extremity blood supply in patients with PAD, with remodeling into the recipient’s own vessel over time. The HAV is currently being evaluated in seven clinical trials to treat PAD, vascular trauma, and as a hemodialysis access conduit. : Clinical Relevance: Patients with peripheral artery disease who require surgical revascularization need options when autologous grafts are not available. The human acellular vessel (HAV) has been demonstrated to have characteristics similar to those of autologous vessels in terms of resistance to infection, mechanics, and a very low risk of rejection. Safety and performance were evaluated for ≤6 years after implantation of an HAV in a femoropopliteal position. Overall, the secondary patency rate estimated using the Kaplan-Meier method was 60% at 72 months, with 45% primary patency. No infection or rejection episodes had occurred with the HAV conduits. These data have demonstrated the durability of the HAV and suggest the occurrence of cellular remodeling by the host. |
| first_indexed | 2024-03-08T18:29:46Z |
| format | Article |
| id | doaj.art-7240c3fbd0244a0c826ab872a7c32cd1 |
| institution | Directory Open Access Journal |
| issn | 2666-3503 |
| language | English |
| last_indexed | 2024-03-08T18:29:46Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JVS - Vascular Science |
| spelling | doaj.art-7240c3fbd0244a0c826ab872a7c32cd12023-12-30T04:44:48ZengElsevierJVS - Vascular Science2666-35032023-01-014100092Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypassPiotr Gutowski, MD, PhD0Malgorzata Guziewicz, MD, PhD1Marek Ilzecki, MD, PhD2Arkadiusz Kazimierczak, MD, PhD3Jeffrey H. Lawson, MD, PhD4Heather L. Prichard, PhD5Stanislaw Przywara, MD, PhD6Rabih Samad, MD, PhD7William Tente, MS8Jakub Turek, MD9Wojcieh Witkiewicz, MD, PhD10Norbert Zapotoczny, MD11Tomaz Zubilewicz, MD, PhD12Laura E. Niklason, MD, PhD13Department of Vascular Surgery and Angiology, Pomeranian Medical University of Szczecin, Szczecin, PolandResearch and Development Centre, Department of Vascular Surgery, General Hospital, Wroclaw, PolandClinic of Vascular Surgery and Angiology, Medical University of Lublin, Lublin, PolandDepartment of Vascular Surgery and Angiology, Pomeranian Medical University of Szczecin, Szczecin, PolandHumacyte, Inc, Durham, NC; Department of Surgery, Duke University, Durham, NCHumacyte, Inc, Durham, NCClinic of Vascular Surgery and Angiology, Medical University of Lublin, Lublin, PolandDepartment of Vascular Surgery and Angiology, Pomeranian Medical University of Szczecin, Szczecin, PolandHumacyte, Inc, Durham, NCResearch and Development Centre, Department of Vascular Surgery, General Hospital, Wroclaw, PolandResearch and Development Centre, Department of Vascular Surgery, General Hospital, Wroclaw, PolandResearch and Development Centre, Department of Vascular Surgery, General Hospital, Wroclaw, PolandClinic of Vascular Surgery and Angiology, Medical University of Lublin, Lublin, PolandHumacyte, Inc, Durham, NC; Department of Anesthesia and Biomedical Engineering, Yale University, New Haven; Department of Biomedical Engineering, Yale University, New Haven, CT; Correspondence: Laura E. Niklason, MD, PhD, Humacyte, Inc, 2525 NC-54, Durham, NC 27713Objective: The human acellular vessel (HAV) was evaluated for surgical bypass in a phase II study. The primary results at 24 months after implantation have been reported, and the patients will be evaluated for ≤10 years. Methods: In the present report, we have described the 6-year results of a prospective, open-label, single-treatment arm, multicenter study. Patients with advanced peripheral artery disease (PAD) requiring above-the-knee femoropopliteal bypass surgery without available autologous graft options had undergone implantation with the HAV, a bioengineered human tissue replacement blood vessel. The patients who completed the 24-month primary portion of the study will be evaluated for ≤10 years after implantation. The present mid-term analysis was performed at the 6-year milestone (72 months) for patients followed up for 24 to 72 months. Results: HAVs were implanted in 20 patients at three sites in Poland. Seven patients had discontinued the study before completing the 2-year portion of the study: four after graft occlusion had occurred and three who had died of causes deemed unrelated to the conduit, with the HAV reported as functional at their last visit. The primary results at 24 months showed primary, primary assisted, and secondary patency rates of 58%, 58%, and 74%, respectively. One vessel had developed a pseudoaneurysm deemed possibly iatrogenic; no other signs of structural failure were reported. No rejections or infections of the HAV occurred, and no patient had required amputation of the implanted limb. Of the 20 patients, 13 had completed the primary portion of the study; however, 1 patient had died shortly after 24 months. Of the remaining 12 patients, 3 died of causes unrelated to the HAV. One patient had required thrombectomy twice, with secondary patency achieved. No other interventions were recorded between 24 and 72 months. At 72 months, five patients had a patent HAV, including four patients with primary patency. For the entire study population from day 1 to month 72, the overall primary, primary assisted, and secondary patency rate estimated using Kaplan-Meier analysis was 44%, 45%, and 60% respectively, with censoring for death. No patient had experienced rejection or infection of the HAV, and no patient had required amputation of the implanted limb. Conclusions: The infection-resistant, off-the-shelf HAV could provide a durable alternative conduit in the arterial circuit setting to restore the lower extremity blood supply in patients with PAD, with remodeling into the recipient’s own vessel over time. The HAV is currently being evaluated in seven clinical trials to treat PAD, vascular trauma, and as a hemodialysis access conduit. : Clinical Relevance: Patients with peripheral artery disease who require surgical revascularization need options when autologous grafts are not available. The human acellular vessel (HAV) has been demonstrated to have characteristics similar to those of autologous vessels in terms of resistance to infection, mechanics, and a very low risk of rejection. Safety and performance were evaluated for ≤6 years after implantation of an HAV in a femoropopliteal position. Overall, the secondary patency rate estimated using the Kaplan-Meier method was 60% at 72 months, with 45% primary patency. No infection or rejection episodes had occurred with the HAV conduits. These data have demonstrated the durability of the HAV and suggest the occurrence of cellular remodeling by the host.http://www.sciencedirect.com/science/article/pii/S2666350322000803Arterial reconstructionBioengineered blood vesselHuman acellular vesselLong-term outcomesPeripheral artery disease |
| spellingShingle | Piotr Gutowski, MD, PhD Malgorzata Guziewicz, MD, PhD Marek Ilzecki, MD, PhD Arkadiusz Kazimierczak, MD, PhD Jeffrey H. Lawson, MD, PhD Heather L. Prichard, PhD Stanislaw Przywara, MD, PhD Rabih Samad, MD, PhD William Tente, MS Jakub Turek, MD Wojcieh Witkiewicz, MD, PhD Norbert Zapotoczny, MD Tomaz Zubilewicz, MD, PhD Laura E. Niklason, MD, PhD Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass JVS - Vascular Science Arterial reconstruction Bioengineered blood vessel Human acellular vessel Long-term outcomes Peripheral artery disease |
| title | Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass |
| title_full | Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass |
| title_fullStr | Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass |
| title_full_unstemmed | Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass |
| title_short | Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass |
| title_sort | six year outcomes of a phase ii study of human tissue engineered blood vessels for peripheral arterial bypass |
| topic | Arterial reconstruction Bioengineered blood vessel Human acellular vessel Long-term outcomes Peripheral artery disease |
| url | http://www.sciencedirect.com/science/article/pii/S2666350322000803 |
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