An Efficacy and Safety Study of SRM003 in the Treatment of Subjects Undergoing Placement of an Arteriovenous Graft to Facilitate Hemodialysis Access

A Phase 2, Single-blind, Randomized, Controlled, Multi-center Study to Evaluate the Efficacy and Safety of SRM003 (Vascugel®) in the Treatment of Subjects With Vascular Injury Resulting From Arteriovenous Graft Surgery for Hemodialysis Access

A study to evaluate the efficacy of SRM003 treatment versus participating sites' standard practice treatment in extending the duration of primary patency after arteriovenous graft surgery in subjects with end-stage renal disease.

It is hypothesized that when placed outside the blood vessel, the seeded SRM003 gelatin matrix containing endothelial cells can provide a continuous supply of multiple growth regulatory compounds to the underlying cells within the blood vessel, while being protected from the effects of blood flow in the vessel(s) or complications resulting from being in direct contact with the point of injury.

Study Overview

• Status: Terminated
• Conditions: Arteriovenous Graft
• Intervention / Treatment: Biological: SRM003; Other: Participating Site's standard practice

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • AKDHC Medical Research Services
    • Tucson, Arizona, United States, 85745
      • Tucson Vascular Consultants
  • California
    • Fresno, California, United States, 93710
      • Ladenheim Dialysis Access Center
    • La Mesa, California, United States, 91942
      • California Institute of Renal Research
    • Long Beach, California, United States, 90822
      • VA Long Beach Health Care System Pharmacy
    • Los Angeles, California, United States, 90025
      • The Regents University of California Los Angeles
    • San Diego, California, United States, 92123
      • California Institute of Renal Research
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8042
      • Yale University School of Medicine
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
  • Illinois
    • Peoria, Illinois, United States, 61603
      • Illinois Kidney Disease & Hypertension Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Baptist Medical Center, Clinical Trials Unit
    • Shreveport, Louisiana, United States, 71130
      • Louisiana State University Health Science Center Shreveport
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center Pharmacy
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Renaissance Renal Research Institute, LLC
    • Petoskey, Michigan, United States, 49770
      • McLaren Northern Michigan Hospital-NISUS Research
    • Southfield, Michigan, United States, 48075
      • Providence Hospital, Research Dept.
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Reno, Nevada, United States, 89511
      • Sierra Nevada Nephrology Consultants
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Johnson City, New York, United States, 13790
      • United Health Services
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine Lab
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Nephrology Associates, PA
    • Greenville, North Carolina, United States, 27834
      • ECU Department of Nephrology and Hypertension
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Research/USD-Fargo
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Physicians Company
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Toledo, Ohio, United States, 43560
      • Toledo Hospital
  • Oregon
    • Milwaukie, Oregon, United States, 97267
      • Kaiser Permanente Northwest
    • Portland, Oregon, United States, 97210
      • Northwest Renal Clinic, Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University School of Medicine
    • Philadelphia, Pennsylvania, United States, 19118
      • Delaware Valley Nephrology and Hypertension Associates, PC
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine, Perelman Center for Advanced Medicine
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • SC Nephrology & Hypertension Center, Inc.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Hospital Pharmacy
    • Nashville, Tennessee, United States, 37205
      • Nephrology Associates, P.C.
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine ICTR
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care Renal Service
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Vascular Specialists
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject must be 18 years of age or older at the time of signing and dating informed consent (no upper age limit), can be male or female.
2. Subject who is of child bearing potential must agree to use adequate contraception for 6 months after randomization.
3. Subject must be currently undergoing hemodialysis or anticipating the start of hemodialysis and must require a new permanent prosthetic expanded polytetrafluoroethylene AVG placed in the upper extremity.
4. Subject must have a life expectancy of at least 78 weeks after randomization.
5. Subject must be able to understand and be willing to complete all study requirements.

Exclusion Criteria:

1. Subject is currently on an active organ transplant list from a deceased donor or is undergoing assessment and expects to be placed on the active organ or bone marrow transplant list within the next 78 weeks from surgery, or expects to receive a living donor organ or bone marrow within the next 78 weeks and is unwilling to change transplant list status to "hold" for 3 months after randomization.
2. Subject has had more than 3 access placement surgeries (defined as a new access, not a revision) in the target limb.
3. Subject has medical conditions and diseases that may cause non-compliance with the protocol
4. Subject has a known allergy to bovine/porcine products or collagen/gelatin products.
5. Subject has a history of intravenous drug use within 6 months prior to screening
6. Subject is morbidly obese, defined as having a body mass index >40.
7. Pregnant or nursing woman, or plans to become pregnant during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: SRM003	Biological: SRM003; One time implant (3 SRM003 pieces) on surgery day.; Other Names: Allogeneic human aortic endothelial cells cultured in a gelatin matrix (Gelfoam®).
OTHER: Participating Site's standard practice	Other: Participating Site's standard practice; Subjects will receive sites' standard practice treatment during the surgical procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Loss of Unassisted Primary Patency	Unassisted primary patency (intervention--free access survival) was defined as the duration of time in days from the date of randomization (arteriovenous graft [AVG] placement) until the first date of (a) any intervention designed to establish, maintain, or restore patency, (b) occlusion (commonly due to thrombosis), or (c) access abandonment. Assessment of AVG patency was evaluated during physical examination of the subject's AVG at each visit and through ongoing AVG monitoring and surveillance according to each participating site's standard practice. It was recommended to follow the National Kidney Foundation Kidney guidelines (National Kidney Foundation 2006) on appropriate management and treatment of AVG complications to improve the function and longevity of the vascular access.	Up to 78 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Loss of Assisted Primary Patency	Assisted primary patency (thrombosis--free access survival) was defined as the duration of time in days from the date of randomization (AVG placement) until the first date of (a) occlusion (commonly due to thrombosis) or (b) access abandonment. Assessment of AVG patency was evaluated during physical examination of the subject's AVG at each visit and through ongoing AVG monitoring and surveillance according to each participating site's standard practice. It was recommended to follow the National Kidney Foundation Kidney guidelines (National Kidney Foundation 2006) on appropriate management and treatment of AVG complications to improve the function and longevity of the vascular access.	Up to 78 weeks after surgery
Percentage of Participants With Loss of Secondary Patency	Secondary patency (access survival until abandonment) was defined as the duration of time in days from the date of randomization (AVG placement) until the date of access abandonment. Assessment of AVG patency was evaluated during physical examination of the subject's AVG at each visit and through ongoing AVG monitoring and surveillance according to each participating site's standard practice. It was recommended to follow the National Kidney Foundation Kidney guidelines (National Kidney Foundation 2006) on appropriate management and treatment of AVG complications to improve the function and longevity of the vascular access.	Up to 78 weeks after surgery
Number of Interventions to Establish, Maintain, or Restore Patency	The total numbers of interventions to establish, maintain, or restore patency was assessed at the Week 26 visit.	26 weeks after surgery

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 28, 2013
• Primary Completion (ACTUAL): October 23, 2014
• Study Completion (ACTUAL): October 23, 2014

Study Registration Dates

• First Submitted: March 5, 2013
• First Submitted That Met QC Criteria: March 6, 2013
• First Posted (ESTIMATE): March 7, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 8, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hemodialysis Access; Vascular Injury; Arteriovenous Graft Surgery
• Additional Relevant MeSH Terms: Hemostatics; Coagulants; Gelatin Sponge, Absorbable
• Other Study ID Numbers: AVG01-SRM003