TY - JOUR
T1 - Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease
T2 - Two phase 2 single-arm trials
AU - Lawson, Jeffrey H.
AU - Glickman, Marc H.
AU - Ilzecki, Marek
AU - Jakimowicz, Tomasz
AU - Jaroszynski, Andrzej
AU - Peden, Eric K.
AU - Pilgrim, Alison J.
AU - Prichard, Heather L.
AU - Guziewicz, Malgorzata
AU - Przywara, Stanisław
AU - Szmidt, Jacek
AU - Turek, Jakub
AU - Witkiewicz, Wojciech
AU - Zapotoczny, Norbert
AU - Zubilewicz, Tomasz
AU - Niklason, Laura E.
N1 - Funding Information:
This work was supported by Humacyte and by the US National Institutes of Health (R44 HL118736). We thank Michael Perelman and Shannon Dahl for assistance with manuscript preparation. William Tente and Juliana Blum assisted with site recruitment and regulatory documents. Justin Strader and Stuart Irwin oversaw graft manufacture, Robert Schutte developed the manufacturing system, and Maribel Santiago did histological analysis. Sally Wade provided editorial assistance.
Funding Information:
This work was supported by Humacyte and by the US National Institutes of Health (R44 HL118736). We thank Michael Perelman and Shannon Dahl for assistance with manuscript preparation.
Publisher Copyright:
© 2016 Elsevier Ltd.
PY - 2016/5/14
Y1 - 2016/5/14
N2 - Background For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. Methods We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. Findings Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47-72) of patients had primary patency, 73% (57-81) had primary assisted patency, and 97% (85-98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17-40) had primary patency, 38% (26-51) had primary assisted patency, and 89% (74-93) had secondary patency. Interpretation Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. Funding Humacyte and US National Institutes of Health.
AB - Background For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. Methods We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. Findings Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47-72) of patients had primary patency, 73% (57-81) had primary assisted patency, and 97% (85-98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17-40) had primary patency, 38% (26-51) had primary assisted patency, and 89% (74-93) had secondary patency. Interpretation Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. Funding Humacyte and US National Institutes of Health.
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U2 - 10.1016/S0140-6736(16)00557-2
DO - 10.1016/S0140-6736(16)00557-2
M3 - Article
C2 - 27203778
AN - SCOPUS:84967239634
VL - 387
SP - 2026
EP - 2034
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10032
ER -