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

Humacyte, Inc.355 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

355

Conditions

Renal Failure End Stage Renal Disease Hemodialysis Vascular Access

Interventions

Human Acellular Vessel (HAV)BIOLOGICAL

HAV-tissue-engineered vascular conduit (6mm diameter)

ePTFE graftDEVICE

One of two commercially available comparators (Bard Impra® and Gore PROPATEN®)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (38)

Outcomes

Primary Outcomes

Number of Participants With Loss of Secondary Patency

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).

Time frame: 12 months post-implantation

Number of Participants With Loss of Secondary Patency

Time frame: 18 months post-implantation

Number of Participants With Loss of Secondary Patency

Time frame: 24 months post-implantation

Secondary Outcomes

Number of Participants With Loss of Primary Patency

Use of duplex ultrasonography to assess study conduit patency. Loss of primary patency occurs when any intervention is performed on the conduit regardless of whether the conduit thrombosed.

Time frame: 12 months post-implantation

Number of Participants With Loss of Primary Patency

Data from ClinicalTrials.gov

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Arizona Kidney Disease and Hypertension Center (AKDHC)

Phoenix, Arizona, United States

Carondelet St. Mary's Hospital

Tucson, Arizona, United States

Ladenheim Dialysis Access Center

Fresno, California, United States

General Surgery and Vascular Access

Fresno, California, United States

University of California Irvine (UCI) Medical Center

Irvine, California, United States

VA Long Beach Healthcare System

Long Beach, California, United States

VA Sacramento Medical Center

Mather, California, United States

Balboa Nephrology

San Diego, California, United States

University of South Florida

Tampa, Florida, United States

Southwest Vascular Access Center

Alsip, Illinois, United States

...and 28 more locations

Use of duplex ultrasonography to assess study conduit patency. Loss of primary patency occurs when any intervention is performed on the conduit regardless of whether the conduit thrombosed.

Time frame: 18 months post-implantation

Number of Participants With Loss of Primary Patency

Use of duplex ultrasonography to assess study conduit patency. Loss of primary patency occurs when any intervention is performed on the conduit regardless of whether the conduit thrombosed.

Time frame: 24 months post-implantation

Number of Participants With Loss of Primary Patency

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.

Time frame: 60 months post-implantation

Study Conduit Abandonment

No remaining segment of the study conduit is incorporated into the vascular access circuit used for dialysis.

Time frame: 24 months post-implantation

Study Conduit Abandonment

No remaining segment of the study conduit is incorporated into the vascular access circuit used for dialysis.

Time frame: 60 months post-implantation

Rate of Adjudicated Study Conduit Access Related Infections

Adjudicated using the standard definition of access-related infections (CDC; 2013).

Time frame: 24 months post-implantation

Access-related Infections

Using Dialysis Event Surveillance Manual: CDC; 2013.

Time frame: 60 months post-implantation

Participants With at Least 1 Intervention Required to Achieve/Maintain Secondary Patency

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.

Time frame: 24 months post-implantation

Total Interventions Performed to Maintain Secondary Patency (Ballon Size Not > 6 Millimeters)

Total number of interventions performed by treatment group stratified by any use of balloon size no \> 6 millimeters.

Time frame: 60 months post-implantation

Total Interventions Performed to Maintain Secondary Patency (Balloon Size > 6 Millimeters)

Total number of interventions performed by treatment group stratified by any use of balloon size greater than 6 millimeters.

Time frame: 60 months post-implantation

Thrombosis of Study Access That Required Intervention

Total number of thrombosis events (per each treatment group) that required an intervention to maintain the functionality of patent access

Time frame: 24 months post-implantation

Thrombosis of Study Access That Required Intervention

Total number of thrombosis events (per each treatment group) that required an intervention to maintain the functionality of patent access

Time frame: 60 months post-implantation

Dialysis Efficiency as Measured by spKt/Vurea (Subset of Subjects)

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.

Time frame: 2 to 18 Months post-implantation

Severity of Adverse Events

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.

Time frame: 24 months post-implantation

Number of Participants With at Least One Adverse Event

Collection of all Adverse Events beginning on Day 0 after implantation up to 2 years post implantation (Month 24).

Time frame: 24 months post-implantation

True Aneurysm Formation (Conduit Lumen Diameter >9 Millimeters)

Assessed by ultrasound: at least a 50% increase over the 6 millimeter baseline

Time frame: 24 months post-implantation

True Aneurysm Formation (Conduit Lumen Diameter >9 Millimeters)

Assessed by ultrasound: at least a 50% increase over the 6 millimeter baseline

Time frame: 60 months post-implantation

Pseudoaneurysm Formation

Use of duplex ultrasound to assess the diameter of the lumen mid-conduit. The outcome measures data represents the total number of pseudoaneurysms.

Time frame: 24 months post-implantation

Pseudoaneurysm Formation

Use of duplex ultrasound to assess the diameter of the lumen mid-conduit. The outcome measures data represents the total number of pseudoaneurysms.

Time frame: 60 months post-implantation

Study Conduit Spontaneous Ruptures Due to Iatrogenic Injury

Assessed by ultrasound

Time frame: 24 months post-implantation

Study Conduit Spontaneous Ruptures Due to Iatrogenic Injury

Assessed by ultrasound

Time frame: 60 months post-implantation

Anastomotic Bleeding or Rupture

Assessed by ultrasound

Time frame: 24 months post-implantation

Anastomotic Bleeding or Rupture

Assessed by ultrasound

Time frame: 60 months post-implantation

Calculated Panel Reactive Antibody More Than 20% Change From Baseline

Increase in Panel Reactive Antibody more than 20% (highly sensitized) from baseline

Time frame: 18 months post-implantation

Calculated Panel Reactive Antibody More Than 20% Change From Baseline

Increase in Panel Reactive Antibody more than 20% (highly sensitized) from baseline

Time frame: 24 months post-implantation

Mean Inner Diameter of Conduit (Millimeter)

Duplex ultrasonography: diameter of the mid-conduit lumen

Time frame: 12 months post-implantation

Mean Inner Diameter of Conduit (Millimeter)

Duplex ultrasonography: diameter of the mid-conduit lumen

Time frame: 24 months post-implantation

Mean Inner Diameter of Conduit (Millimeter)

Duplex ultrasonography: diameter of the mid-conduit lumen

Time frame: 60 months post-implantation