Comparison of the Human Acellular Vessel (HAV) With ePTFE Grafts as Conduits for Hemodialysis

Phase 3

Completed

Conditions: Renal Failure
End Stage Renal Disease
Hemodialysis
Vascular Access

Interventions: Device: ePTFE graft
Biological: Human Acellular Vessel (HAV)

Registration Number: NCT02644941

Lead Sponsor: Humacyte, Inc.

Brief Summary: The main purpose of this study is to compare the Human Acellular Vessel (HAV) with ePTFE grafts when used for hemodialysis access.

Detailed Description: This is a Phase 3, prospective, multicenter, multinational, open-label, randomized, two-arm, comparative study. Subjects who sign informed consent would undergo study-specific screening assessments within 35 days from the day of informed consent.

Participants who consented were randomized to the HAV treatment arm of one of the two commercially available comparators.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 355

Inclusion Criteria

Subjects with ESRD who need placement of an AV graft in the arm.
Either on hemodialysis or expected to start hemodialysis within 12 weeks of study conduit implantation.
Suitable anatomy for implantation of straight or looped conduits in either the forearm or upper arm (not crossing the elbow).
Hemoglobin ≥8 g/dL and platelet count ≥100,000 cells/mm3 prior to Day 0 (within 35 days).
Other hematological and biochemical parameters within a range consistent with ESRD prior to Day 0 (within 35 days).
Adequate liver function prior to Day 0 (within 35 days).
Female subjects must be either:
- Of non-childbearing potential Or
- Must agree to use at least one form of birth control methods for the duration of the study.
Subject, or legal representative, able to communicate effectively with investigative staff, competent and willing to give written informed consent, and able to comply with entire study procedures including all scheduled follow-up visits.
Life expectancy of at least 1 year.

Exclusion Criteria

History or evidence of severe peripheral vascular disease in the intended arm for implantation.
Known or suspected central vein stenosis or conduit occlusion on the ipsilateral side of planned implantation, unless the stenosis is corrected prior to study conduit implantation.
Treatment with any investigational drug or device within 60 days prior to study entry (Day 0).
Cancer that is actively being treated with a cytotoxic agent.
Documented hyper-coagulable state.
Bleeding diathesis.
Active clinically significant immune-mediated disease, not controlled by maintenance immunosuppression.
High dose glucocorticoid therapy for treatment of autoimmune flare, or other inflammatory diseases is excluded.
Patients using glucocorticoids for immunosuppression post-transplant to prevent against transplanted allograft rejection in the period post allograft failure are excluded.
The following examples of immunosuppressive agents (or the like) are exclusionary for enrollment in this clinical trial:
tacrolimus or FK506 [Prograf]
mycophenolate mofetil [Cellcept],
cyclosporine [Sandimmune or Gengraf] i-Sirolimus administered systemically (Sirolimus in drug eluting stents is NOT an exclusion)
Anticipated renal transplant within 6 months.
Venous outflow from study conduit cannot be placed more centrally than the venous outflow of any previous failed access in that extremity.
Active local or systemic infection (white blood cells [WBC] > 15,000 cells/mm3 at Screening). If the infection resolves, the subject must be at least one week post resolution of that infection before implantation.
Known serious allergy to planned antiplatelet agent.
Pregnant women, or women intending to become pregnant during the course of the trial.
Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the study conduit.
Previous enrollment in this study or any other study with the HAV.
Employees of Humacyte and employees or relatives of the investigator.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ePTFE	ePTFE graft	The comparator (one of two commercially available 6mm ePTFE grafts) will be surgically implanted in the forearm or upper arm on Study Day 0.
Human Acellular Vessel (HAV)	Human Acellular Vessel (HAV)	The HAV is a tissue-engineered vascular conduit (6mm diameter) for hemodialysis access in patients with end-stage renal disease. It will be surgically implanted in the forearm or upper arm on Study Day 0.
Human Acellular Vessel (HAV)	Human Acellular Vessel (HAV)	HAV-tissue-engineered vascular conduit (6mm diameter)
ePTFE	ePTFE graft	One of two commercially available comparators (Bard Impra® and Gore PROPATEN®)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Loss of Secondary Patency	24 months post-implantation	1. Defined as 'the interval from the time of access placement until access abandonment', i.e., patent with or without interventions (Sidawy et al. 2002). 2. "Abandonment" defined as no remaining segment of the study conduit was incorporated into the vascular access circuit used for dialysis (conversely, if some portion of the study conduit was still being used for dialysis it was not considered abandoned).

Secondary Outcome Measures

Name	Time	Method
Study Conduit Abandonment	60 months post-implantation	No remaining segment of the study conduit is incorporated into the vascular access circuit used for dialysis.
Rate of Adjudicated Study Conduit Access Related Infections	24 months post-implantation	Adjudicated using the standard definition of access-related infections (CDC; 2013).
Access-related Infections	60 months post-implantation	Using Dialysis Event Surveillance Manual: CDC; 2013.
Participants With at Least 1 Intervention Required to Achieve/Maintain Secondary Patency	24 months post-implantation	Rate of intervention defined as the number of interventions per participant per year while conduit is patent (i.e., has not been abandoned). Number of successful interventions to achieve/maintain Secondary Patency.
Total Interventions Performed to Maintain Secondary Patency (Ballon Size Not > 6 Millimeters)	60 months post-implantation	Total number of interventions performed by treatment group stratified by any use of balloon size no \> 6 millimeters.
Total Interventions Performed to Maintain Secondary Patency (Balloon Size > 6 Millimeters)	60 months post-implantation	Total number of interventions performed by treatment group stratified by any use of balloon size greater than 6 millimeters.
Thrombosis of Study Access That Required Intervention	60 months post-implantation	Total number of thrombosis events (per each treatment group) that required an intervention to maintain the functionality of patent access
Pseudoaneurysm Formation	60 months post-implantation	Use of duplex ultrasound to assess the diameter of the lumen mid-conduit. The outcome measures data represents the total number of pseudoaneurysms.
Study Conduit Spontaneous Ruptures Due to Iatrogenic Injury	60 months post-implantation	Assessed by ultrasound
Anastomotic Bleeding or Rupture	60 months post-implantation	Assessed by ultrasound
Calculated Panel Reactive Antibody More Than 20% Change From Baseline	24 months post-implantation	Increase in Panel Reactive Antibody more than 20% (highly sensitized) from baseline
Mean Inner Diameter of Conduit (Millimeter)	60 months post-implantation	Duplex ultrasonography: diameter of the mid-conduit lumen
Number of Participants With Loss of Primary Patency	60 months post-implantation	Duplex ultrasound was used to assess study conduit patency. Loss of primary patency occurs when any intervention is performed on the conduit regardless of whether the conduit thrombosed.
Dialysis Efficiency as Measured by spKt/Vurea (Subset of Subjects)	2 to 18 Months post-implantation	Dialysis efficiency as assessed by spKt/Vurea (obtained from dialysis unit for a subset of subjects) will be summarized descriptively. The most recent available data prior to the study visits will be used for the analysis. Twenty sites provided at least 1 spKt/Vurea measurement. spKt/Vurea: measure of dialysis adequacy for a single hemodialysis treatment using the single pooled method.
Severity of Adverse Events	24 months post-implantation	Severity Assessment Standard 1. Mild: Events require minimal or no treatment and do not interfere with the subject's daily activities. 2. Moderate: Events result in a low level of inconvenience or concern with the therapeutic measures. May cause some interference with functioning. 3. Severe: Events interrupt a subject's usual daily activity and may require systemic drug therapy or other treatment. Severe events are usually incapacitating. 4. Life-threatening: Any adverse event that places the subject or participant, in the view of the investigator, at immediate risk of death from the reaction as it occurred, i.e., it does not include a reaction that, had it occurred in a more severe form, might have caused death. 5. Death: Death related to Adverse Event.
Number of Participants With at Least One Adverse Event	24 months post-implantation	Collection of all Adverse Events beginning on Day 0 after implantation up to 2 years post implantation (Month 24).
True Aneurysm Formation (Conduit Lumen Diameter >9 Millimeters)	60 months post-implantation	Assessed by ultrasound: at least a 50% increase over the 6 millimeter baseline

Trial Locations

Locations (38): General Surgery and Vascular Access
🇺🇸
Fresno, California, United States
University of California Irvine (UCI) Medical Center
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Irvine, California, United States
VA Sacramento Medical Center
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Mather, California, United States
University of South Florida
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Tampa, Florida, United States
University of Maryland Medical Center
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Baltimore, Maryland, United States
Michigan Cardiovascular Institute
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Flint, Michigan, United States
Washington University School of Medicine
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Saint Louis, Missouri, United States
Rutgers-New Jersey Medical School
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Newark, New Jersey, United States
The Cardiovascular Care Group
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Westfield, New Jersey, United States
Duke University Hospital
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Durham, North Carolina, United States
Medical University of South Carolina (MUSC)
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Orangeburg, South Carolina, United States
Baylor Scott and White Research Institute
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Dallas, Texas, United States
Yitzhak Shamir Medical Center - Assaf Harofeh
🇮🇱
Tzrifin, Israel
Samodzielny Publiczyn Centralny Szpital Klinziczny w Warszawie - Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
🇵🇱
Warszawa, Poland
Wojewódzki Szpital Specjalistyczny we Wrocławiu
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Wroclaw, Poland
Grupo de Estudos Vasculares
🇵🇹
Porto, Portugal
Queen Elizabeth Hospital Birmingham
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Birmingham, West Midlands, United Kingdom
Queen Elizabeth University Hospital Glasgow
🇬🇧
Glasgow, United Kingdom
Arizona Kidney Disease and Hypertension Center (AKDHC)
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Phoenix, Arizona, United States
Carondelet St. Mary's Hospital
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Tucson, Arizona, United States
Ladenheim Dialysis Access Center
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Fresno, California, United States
VA Long Beach Healthcare System
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Long Beach, California, United States
Balboa Nephrology
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San Diego, California, United States
Southwest Vascular Access Center
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Alsip, Illinois, United States
Brigham and Women's Hospital
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Boston, Massachusetts, United States
Greenwood Leflore Hospital
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Greenwood, Mississippi, United States
Kaiser Permanente
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Portland, Oregon, United States
University of Wisconsin
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Madison, Wisconsin, United States
Universitätsklinikmn Erlangen, Gefäßchirurgie - Chirurgisches Zentrum
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Erlangen, Bayern, Germany
Universitätsklinikum Frankfurt Klinik für Gefäß- und Endovascular-Chirurgie
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Frankfurt/Main, Hessen, Germany
The Chaim Sheba Medical Center
🇮🇱
Ramat Gan, Tel-Aviv, Israel
Hillel Jaffe Medical Center
🇮🇱
Hadera, Israel
Rambam Health Care Campus
🇮🇱
Haifa, Israel
Sharee Zedek Medical Center
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Jerusalem, Israel
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
🇵🇱
Poznan, Poland
Leicester General Hospital
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Leicester, East Midlands/ Leicestershire, United Kingdom
Guy´s Hospital, Kings´College London
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London, Greater London, United Kingdom
Leeds General Infirmary
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Leeds, United Kingdom