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

A Phase 2, Single-blind, Randomized, Controlled, Multi-center Study to Evaluate the Efficacy and Safety of SRM003 (Vascugel®) in Improving the Rate of Arteriovenous Fistula Maturation and Use in Subjects Undergoing Surgery for Creation of an Arteriovenous Fistula for Hemodialysis Access

A study to evaluate the efficacy of SRM003 treatment versus participating sites' standard practice treatment in improving the rate of AVF maturation and use in subjects with end-stage renal disease undergoing surgery for creation of an AVF to facilitate hemodialysis access.

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: Completed
• Conditions: Arteriovenous Fistula
• Intervention / Treatment: Biological: SRM003; Other: Participating Site's standard practice

• Study Type: Interventional
• Enrollment (Actual): 64
• 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
  • Washington
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center
  • 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, suitable access for the AVF creation in the upper extremity.
4. Subject must have a life expectancy of at least 26 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 26 weeks from surgery, or expects to receive a living donor organ or bone marrow within the next 26 weeks and is unwilling to change transplant list status to "hold" for 3 months after randomization.
2. Subject has had more than 1 access placement surgery (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 Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SRM003; One time implant (2 SRM003 pieces) on surgery day. Post-surgery, up to 26 weeks follow-up for assessment of efficacy/safety.	Biological: SRM003; One time implant (2 SRM003 pieces) on surgery day.; Other Names: Allogeneic human aortic endothelial cells cultured in a gelatin matrix (Gelfoam®).
Other: Participating Site's standard practice; Subjects will receive sites' standard practice treatment during the surgical procedure.	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 Arteriovenous Fistula (AVF) Maturation by Week 12 Visit Based on Hemodialysis or Color-flow Doppler Ultrasound (CDUS) And Vascular Access Examination	Maturation based on CDUS was assessed in a continuous fashion and was defined by the following criteria: presence of bruit throughout systole and diastole at least 8 centimeters (cm) proximal to the venous anastomosis, blood flow through the outflow vein of at least 500 milliliters (ml) per minute, and a lumen diameter of the outflow vein at least 4 mm. Maturation was determined by CDUS and vascular access examination or by first use of the AVF for hemodialysis based on investigator-reported use. Participants who discontinued prior to the Week 12 visit without assessment of maturity were considered treatment failures.	12 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With AVF Maturation by Week 26 Visit Based on Hemodialysis or CDUS And Vascular Access Examination	Maturation based on CDUS was assessed in a continuous fashion and was defined by the following criteria: presence of bruit throughout systole and diastole at least 8 centimeters (cm) proximal to the venous anastomosis, blood flow through the outflow vein of at least 500 milliliters (ml) per minute, and a lumen diameter of the outflow vein at least 4 mm. Maturation was determined by CDUS and vascular access examination or by first use of the AVF for hemodialysis based on investigator-reported use. Participants who discontinued prior to the Week 26 visit without assessment of maturity were considered treatment failures.	26 weeks after surgery
Time to AVF Maturation Based on Hemodialysis or CDUS and Vascular Access Examination	Time to AVF maturation was defined as the duration of time (in days) from the date of randomization (AVF creation) to the date of maturation, where the date of maturation corresponds to the earlier of either the date of the first use of the study AVF for hemodialysis as determined by the investigator following discussion with the participant, or the date the AVF meets all of the following 3 criteria as determined through CDUS and vascular access examination: presence of bruit throughout systole and diastole at least 8 centimeters proximal to the venous anastomosis, blood flow through the outflow vein of at least 500 milliliters (ml) per minute, and a lumen diameter of the outflow vein at least 4 mm. Participants who died, underwent a kidney transplant, or were either lost to follow-up or did not mature during the study follow-up were censored at the time of death, time of transplant, or time of last visit, respectively.	Up to 26 weeks after surgery
Percentage of Participants With Loss of Unassisted Primary Patency	The time to loss of unassisted primary patency (intervention--free access survival) was defined as the duration of time in days from the date of randomization (AVF creation) 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.	Up to 26 weeks after surgery
Percentage of Participants With Loss of Assisted Primary Patency	The time to loss of assisted primary patency (thrombosis--free access survival) was defined as the duration of time in days from the date of randomization (AVF creation) until the first date of (a) occlusion (commonly due to thrombosis) or (b) access abandonment.	Up to 26 weeks after surgery
Percentage of Participants With Loss of Secondary Patency	The time to loss of secondary patency (access survival until abandonment) was defined as the duration of time in days from the date of randomization (AVF creation) until the date of access abandonment.	Up to 26 weeks after surgery
Change From Week 1 in Average Vascular Access Lumen Diameter Using CDUS	B-mode lumen diameter measurements were obtained in the outflow vein as 3 separate images for each location: at 1, 3, and 5 centimeter into the vein and from the toe of the venous anastomosis. The average of lumen diameter measurements obtained at 1, 3, and 5 cm from the anastomosis was used for this endpoint.	1, 12, and 26 weeks after surgery
Percentage of Participants With Clinical Success Based on First Use of The Study AVF For Hemodialysis	Clinical success was defined as the ability to undergo hemodialysis using the AVF. The date of clinical success corresponded to the date of the first use of the study AVF for hemodialysis as determined by the investigator, following discussion with the subject. Clinical success was assessed in a continuous fashion and, once achieved, the AVF was considered a clinical success at that and all subsequent time points. The date of clinical success based on the first use of the AVF for hemodialysis was compared with the dates of each study visit (Week 12 and Week 26); for study visits occurring prior to the date of clinical success based on the first use of the AVF for hemodialysis, the subject was counted as a nonsuccess and for study visits occurring on or after the date of maturation based on the first use of the AVF for hemodialysis, the subject was counted as a success.	12 and 26 weeks after surgery
Number of Interventions to Establish, Maintain, or Restore Patency	The total number of interventions to establish, maintain, or restore patency was recorded for each participant.	12 and 26 weeks after surgery

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2013
• Primary Completion (Actual): October 27, 2014
• Study Completion (Actual): October 27, 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 Fistula Surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Pathological Conditions, Anatomical; Cardiovascular Abnormalities; Vascular Malformations; Arteriovenous Malformations; Vascular Fistula; Fistula; Arteriovenous Fistula; Hemostatics; Coagulants; Gelatin Sponge, Absorbable
• Other Study ID Numbers: AVF01-SRM003