Clinical trial NCT05908084: To Compare the Efficacy and Safety of the ATEV With AVF in Female Patients With End-Stage Renal Disease Requiring Hemodialysis
Official title: A Phase 3 Randomized Study to Compare the Efficacy and Safety of the Humacyte Acellular Tissue Engineered Vessel (ATEV) With That of an Autogenous Arteriovenous Fistula (AVF) in Female Patients With End-Stage Renal Disease Requiring Hemodialysis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: End Stage Renal Disease (ESRD)
Keywords: hemodialysis (HD)
dialysis catheter
Lead sponsor: Humacyte, Inc.
Sponsor class: INDUSTRY
Collaborators: name: IQVIA Biotech
First posted: 2023-06-18
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized 1:1 to either the ATEV or the AVF treatment arm.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare the number of catheter-free days (CFD) and the rate and severity of any dialysis access-related infections between the ATEV and AVF groups over 12 months in patients with end-stage renal disease (ESRD) needing hemodialysis (HD).

Participants will be stratified by location of the vascular access (forearm versus upper arm) and by type of AVF creation procedure planned by the surgeon at randomization (1-stage AVF versus 2-stage AVF). The comparator is an upper extremity arterio-venous fistula (AVF) for HD access surgically created per the institution's Standard of Care (SoC).

Detailed description: This is a prospective, multicenter, randomized, two-arm, comparative Phase 3 study of female patients with ESRD, who are receiving clinically successful hemodialysis (HD) via a central venous dialysis catheter (DC).

Approximately 150 female patients will be randomized 1:1 to either the ATEV or the AVF treatment arm. Patients will be stratified by location of the vascular access (forearm versus upper arm) and by type of AVF creation procedure planned by the surgeon at randomization (1-stage AVF versus 2-stage AVF).

All patients will be followed through Month 12 regardless of SA patency status. Patients who have a patent SA at Month 12 will then be followed in the Long-Term Extension study for an additional 12 months with evaluation of exploratory long-term endpoints.

Eligibility criteria: Inclusion Criteria:

1. Female patients with ESRD, currently receiving hemodialysis via dialysis catheter and who are candidates for the creation of an AVF (see Inclusion Criterion #4 below) or implantation of an ATEV for HD access.
2. Patients who plan to undergo HD at a dialysis unit of a participating dialysis provider for at least 12 months after SA creation.
3. Patients aged ≥ 18 years at Screening.
4. Suitable anatomy for creation of a forearm or upper arm AVF and for implantation of straight, curved, or looped ATEV in either the forearm or upper arm.

   NOTE: Suitable anatomy will be determined by both physical examination and ultrasound imaging or vessel imaging modality in addition to consideration of all vascular sites available, prior access failure, future access sites and possibilities to preserve patients' future alternate accesses. Vessel mapping is the preferred method to assess the vascular anatomy, and will evaluate the following attributes during Screening:
   * Vein diameter
   * Arterial diameter
   * Presence of arterial calcification
   * Depth of the intended fistula conduit from the surface of the skin
   * Central vein patency
   * Previous vascular access location The ultimate decision of anatomic suitability belongs to the surgeon and/or the investigator.
5. Hemoglobin ≥ 7 g/dL and platelet count ≥ 100,000 /mm3
6. Patients must either:

   1. Be of non-childbearing potential, which is defined as post-menopausal (at least 1 year without menses prior to Screening) or documented surgically sterile (i.e., total hysterectomy or tubal ligation, or complete bilateral oophorectomy) at least 1 month prior to Screening.
   2. Or, if of childbearing potential:

   Must have a negative serum pregnancy test at Screening, and

   Must agree to use at least one form of the following birth control methods for the duration of the study:

   i. Established use of oral, injectable or implanted hormonal methods of contraception.

   ii. Placement of an intrauterine device or intrauterine system at least 5 days prior to Screening.

   iii. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/ gel/ film/ cream/ suppository.
7. Patient or their legal representative can communicate effectively with investigative staff, is competent and willing to give written informed consent, and able to comply with entire study procedures including all scheduled follow-up visits.
8. Life expectancy of at least 1 year confirmed by Charlson Comorbidity Index ≤ 9.

Exclusion Criteria:

1. Male sex at birth.
2. Planned AVF creation by means other than suture or vascular anastomotic clips (e.g., endovascular surgery or other anastomotic creation devices). Venous outflow from study access cannot be located more distally than the venous outflow of any previous failed access in that extremity.
3. Known serious allergy or intolerance to aspirin and alternative antiplatelet therapy.
4. Pregnancy, or women intending to become pregnant during the course of the trial.
5. Treatment with any investigational drug or device within 60 days or 5 half-lives after taking the last dose (whichever is longer) prior to study entry (Day 1) or ongoing participation in a clinical trial of an investigational product.
6. Documented hyper-coagulable state, as defined as either:

   1. Documented hyper-coagulable state, as defined as either: A biochemical diagnosis (e.g., Factor V Leiden, Protein C deficiency, etc.) - OR -
   2. A clinical history of thrombophilia as diagnosed by 2 or more spontaneous intravascular thrombotic events (e.g., deep vein thrombosis (DVT), pulmonary embolism (PE), etc.) within the previous 5 years.
7. Spontaneous or unexplained bleeding diathesis clinically documented within the last 5 years or a biochemical diagnosis (e.g., von Willebrand's disease, etc.).
8. Cancer actively being treated with a cytotoxic agent.
9. Planned or anticipated renal transplant within 6 months after randomization.
10. Any other condition that in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the SA.
11. Previous exposure to ATEV.
12. Any of the following within 8 weeks prior to screening: acute coronary syndrome, stroke or congestive heart failure NYHA Stage IV
13. Employees of Humacyte and employees or relatives of an investigator.

Primary outcomes:
measure: The number of catheter-free days since randomization to Month 12.
timeFrame: 12 months
measure: The rate of infections related to any HD access.
timeFrame: 12 months
Secondary outcomes:
measure: The number of catheter-free days since randomization to Month 6.
timeFrame: 6 months
measure: The number of days of the study access (SA) functional patency
timeFrame: 12 months
measure: The rate of the study access (SA) secondary patency
timeFrame: 6 - 12 months
measure: The number of days from the study access (SA) maturation to abandonment
timeFrame: 12 months
measure: The rate of complications related to any HD access after the study access (SA) creation.
timeFrame: 12 months
Other outcomes:
measure: Incidence rate of HD access-related interventions
timeFrame: 12 months
measure: The number of days from randomization to first day of functional dialysis
timeFrame: 12 months
measure: Incidence rate of Study Access (SA) abandonment
timeFrame: 12 months
measure: Health-related quality of life (HRQoL) of patients (a scale from 0 to 45, with higher scores meaning best outcome)
timeFrame: 12 months
measure: Vascular Access Questionnaire (VAQ) score (range 0-68 with higher scores mean worst outcome).
timeFrame: 12 months
measure: The incidence rate of aneurysm or pseudoaneurysm
timeFrame: 12 months
measure: The incidence rate of adverse events (AEs)
timeFrame: 12 months
Locations:
city: Scottsdale
country: United States
facility: Honor Health Scottsdale Shea Medical Center
state: Arizona
city: El Centro
country: United States
facility: El Centro Regional Medical Center
state: California
city: La Jolla
country: United States
facility: Jacob's Medical Center at UC San Diego Health
state: California
city: Denver
country: United States
facility: Denver Health and Hospital Authority
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Brooksville
country: United States
facility: Access Research Institute
state: Florida
city: Gainesville
country: United States
facility: University of FL Health Heart and Vascular Hospital
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: American Access Care of Miami, LLC
state: Florida
city: Tampa
country: United States
facility: USF Health South Tampa
state: Florida
city: Atlanta
country: United States
facility: Georgia Nephrology
state: Georgia
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Bloomington
country: United States
facility: IU Health Bloomington Hospital
state: Indiana
city: Baltimore
country: United States
facility: John Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Newark
country: United States
facility: Rutgers University_Medical
state: New Jersey
city: Paterson
country: United States
facility: St.Joseph's University Medical Center
state: New Jersey
city: Pennington
country: United States
facility: Capital Health Medical Center- Hopewell
state: New Jersey
city: Flushing
country: United States
facility: New York-Presbyterian Queens_The Lang Center for Research & Education
state: New York
city: Valhalla
country: United States
facility: Ambulatory Care Pavilion Westchester Medical Center
state: New York
city: Charlotte
country: United States
facility: Surgical Specialists of Charlotte
state: North Carolina
city: Durham
country: United States
facility: Duke Regional Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine_Atrium Health Wake Forest Baptist
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Austin
country: United States
facility: Dell Seton Medical Center at The University of Texas at Austin
state: Texas
city: Lubbock
country: United States
facility: Dr. Ruben Villa__Nephrology
state: Texas
city: Lubbock
country: United States
facility: Cataract & Surgery Center Lubbock
state: Texas
city: San Antonio
country: United States
facility: San Antonio Vascular and Endovascular Clinic PLLC
state: Texas
city: San Antonio
country: United States
facility: The San Antonio Vascular and Endovascular Clinic
state: Texas
Study officials:
References: