Comparison of Humacyte's Human Acellular Vessel with ePTFE grafts V1.2
Research type
Research Study
Full title
An assessment of Humacyte's Human Acellular Vessel in Patients needing Renal Replacement Therapy: A Comparison with ePTFE Grafts as conduits for Hemodialysis
IRAS ID
203334
Contact name
Nicolas Inston
Contact email
Sponsor organisation
Humacyte
Eudract number
2015-003261-28
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 4 months, 1 days
Research summary
A Phase 3 comparative study to assess Humacyte's Human Acellular Vessel compared to ePTFE grafts in Patients needing renal replacement therapy. A total of 350 patients will be enrolled with a 1:1 randomization process, 175 patients with Human Acellular Vessel (HAV) and 175 with an expanded polytetrafluroethylene (ePTFE) graft. This is a multinational,multicentre, open label randomized two arm comparative study.
Lay Summary of Study Results:
A total of 355 adults (176 men and 179 women) with end-stage kidney disease participated in this trial. Participants, ranging in age from 19 to 88 years, required a vascular graft for hemodialysis. The study was conducted across six countries: Germany, Israel, Poland, Portugal, the United Kingdom, and the United States.The study did not demonstrate that the Human Acellular Vessel (HAV) was non-inferior to the synthetic ePTFE graft in terms of long-term use as a vascular access for hemodialysis. Both graft types showed similar durability, with low rates of failure (loss of secondary patency) up to 60 months after implantation.
Safety:
In this study, researchers found that the HAV conduit was associated with a higher rate of side effects than the ePTFE graft. Common side effects in the HAV group included thrombosis, vascular stenosis, and pseudoaneurysms. Serious side effects occurred in 55% of HAV patients compared to 47% in the ePTFE group, though none of the patient deaths during the study were linked to the grafts themselves.What Treatments did the participants receive?
Participants received either the Human Acellular Vessel (HAV), a biologically engineered vessel derived from human tissue, or the synthetic ePTFE graft, a commonly used plastic graft for vascular access.
No placebo was used in this trial.Participants were randomly assigned to one of the two treatment groups (HAV or ePTFE graft) using a computer program. This was an open-label study, meaning both the participants and the study staff knew which graft each participant received.
What medical problems (side effects) did the participants have?
Side effects related to the use of either the Human Acellular Vessel (HAV) or ePTFE graft were reported and included several at the vascular access site, such as thrombosis (blood clots), vascular stenosis (narrowing of blood vessels), and pseudoaneurysms (injury and blood leakage). Thrombosis was the most common, affecting 118 of 177 patients (67%) in the HAV group and 88 of 178 patients (49%) in the ePTFE group, indicating a possible causal relationship with the grafts used.Classified as life-threatening events, those requiring hospitalisation, resulting in lasting health issues, or deemed medically significant, SAEs were more frequent in the HAV group. A total of 97 out of 177 patients (55%) in the HAV group and 83 out of 178 patients (47%) in the ePTFE group experienced SAEs.
Thrombosis: 67% of HAV patients (118 out of 177) and 49% of ePTFE patients (88 out of 178).
Vascular Stenosis: 74% of HAV patients (131 out of 177) and 63% of ePTFE patients (112 out of 178).
Pseudoaneurysm: 40% of HAV patients (70 out of 177) and 19% of ePTFE patients (34 out of 178).
Haemorrhage (Bleeding): 17% of HAV patients (30 out of 177) and 15% of ePTFE patients (26 out of 178).
Haematoma (Bruise): 11% of HAV patients (19 out of 177) and 7% of ePTFE patients (13 out of 178).
Infection at the Vascular Access Site: 2% of HAV patients (4 out of 177) and 10% of ePTFE patients (17 out of 178).In total, 38% of HAV patients (68 out of 177) and 37% of ePTFE patients (65 out of 178) passed away during the study, with no deaths attributed to the grafts. Additionally, 18% of HAV patients (32 out of 177) and 16% of ePTFE patients (29 out of 178) discontinued the study due to symptoms.
Participants were divided into two groups. One group received the Human Acellular Vessel (HAV), a bioengineered graft derived from human tissue, while the other received the synthetic ePTFE graft, a plastic-based vascular access commonly used in haemodialysis.
The study had a neutral outcome. While the HAV did not demonstrate clear non-inferiority to the ePTFE graft based on the study's pre-specified analysis, both grafts provided similar long-term use for haemodialysis access.
The main goal was to measure the time from graft implantation until "loss of secondary patency," which is when the graft can no longer be used for dialysis. The study did not find HAV to be non-inferior to ePTFE in maintaining secondary patency over time.
Side Effect Profile: The study examined common side effects such as thrombosis, vascular stenosis, and pseudoaneurysm. It was observed that while the HAV had a higher rate of certain adverse events, the differences in the overall safety profiles of HAV and ePTFE were comparable.
Duration of Use: The average time each graft type was used for dialysis was similar, with HAV grafts averaging 764 days and ePTFE grafts averaging 801 days.
The study concluded neutrally, indicating that while HAV showed potential as an alternative to ePTFE for haemodialysis, there was insufficient evidence to confirm it performs as well as or better than ePTFE. Additional studies may help to clarify its effectiveness and safety compared to standard synthetic grafts.
A major limitation was that the study did not include enough participants to demonstrate conclusively that the HAV is non-inferior to ePTFE. Additionally, the study's design and the lower-than-expected rate of graft failure in the ePTFE group may have impacted the ability to detect meaningful differences between the two grafts. These factors limited the strength of the conclusions that could be drawn regarding the HAV's performance relative to ePTFE.
It is essential to understand that the outcome of this study reflects only one clinical trial. Results may vary in other studies, and additional research may help clarify the long-term effectiveness and safety of HAV grafts compared to standard synthetic grafts like ePTFE.
As with any medical treatment, patients should discuss these findings with their healthcare professional before making any changes to their treatment plan.
REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
16/WM/0215
Date of REC Opinion
14 Jul 2016
REC opinion
Further Information Favourable Opinion