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

Phase 2

Completed

Conditions: Arteriovenous Fistula

Interventions: Biological: SRM003
Other: Participating Site's standard practice

Registration Number: NCT01806545

Lead Sponsor: Shire

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 64

Inclusion Criteria

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.
Subject who is of child bearing potential must agree to use adequate contraception for 6 months after randomization.
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.
Subject must have a life expectancy of at least 26 weeks after randomization.
Subject must be able to understand and be willing to complete all study requirements.

Exclusion Criteria

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.
Subject has had more than 1 access placement surgery (defined as a new access, not a revision) in the target limb.
Subject has medical conditions and diseases that may cause non-compliance with the protocol
Subject has a known allergy to bovine/porcine products or collagen/gelatin products.
Subject has a history of intravenous drug use within 6 months prior to screening
Subject is morbidly obese, defined as having a body mass index >40.
Pregnant or nursing woman, or plans to become pregnant during the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SRM003	SRM003	One time implant (2 SRM003 pieces) on surgery day. Post-surgery, up to 26 weeks follow-up for assessment of efficacy/safety.
Participating Site's standard practice	Participating Site's standard practice	Subjects will receive sites' standard practice treatment during the surgical procedure.

Primary Outcome Measures

Name	Time	Method
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	12 weeks after surgery	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Success Based on First Use of The Study AVF For Hemodialysis	12 and 26 weeks after surgery	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.
Percentage of Participants With Loss of Unassisted Primary Patency	Up to 26 weeks after surgery	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.
Percentage of Participants With AVF Maturation by Week 26 Visit Based on Hemodialysis or CDUS And Vascular Access Examination	26 weeks after surgery	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.
Time to AVF Maturation Based on Hemodialysis or CDUS and Vascular Access Examination	Up to 26 weeks after surgery	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.
Percentage of Participants With Loss of Assisted Primary Patency	Up to 26 weeks after surgery	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.
Percentage of Participants With Loss of Secondary Patency	Up to 26 weeks after surgery	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.
Change From Week 1 in Average Vascular Access Lumen Diameter Using CDUS	1, 12, and 26 weeks after surgery	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.
Number of Interventions to Establish, Maintain, or Restore Patency	12 and 26 weeks after surgery	The total number of interventions to establish, maintain, or restore patency was recorded for each participant.

Trial Locations

Locations (46): Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States
Ochsner Baptist Medical Center, Clinical Trials Unit
🇺🇸
New Orleans, Louisiana, United States
McLaren Northern Michigan Hospital-NISUS Research
🇺🇸
Petoskey, Michigan, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
SC Nephrology & Hypertension Center, Inc.
🇺🇸
Orangeburg, South Carolina, United States
University of Wisconsin
🇺🇸
Madison, Wisconsin, United States
Louisiana State University Health Science Center Shreveport
🇺🇸
Shreveport, Louisiana, United States
ECU Department of Nephrology and Hypertension
🇺🇸
Greenville, North Carolina, United States
Delaware Valley Nephrology and Hypertension Associates, PC
🇺🇸
Philadelphia, Pennsylvania, United States
Erlanger Hospital Pharmacy
🇺🇸
Chattanooga, Tennessee, United States
Fletcher Allen Health Care Renal Service
🇺🇸
Burlington, Vermont, United States
University of Cincinnati Physicians Company
🇺🇸
Cincinnati, Ohio, United States
Baylor College of Medicine ICTR
🇺🇸
Houston, Texas, United States
Ladenheim Dialysis Access Center
🇺🇸
Fresno, California, United States
University of Louisville
🇺🇸
Louisville, Kentucky, United States
Baystate Medical Center Pharmacy
🇺🇸
Springfield, Massachusetts, United States
Mount Sinai School of Medicine Lab
🇺🇸
New York, New York, United States
The Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Penn Medicine, Perelman Center for Advanced Medicine
🇺🇸
Philadelphia, Pennsylvania, United States
Sentara Vascular Specialists
🇺🇸
Norfolk, Virginia, United States
Akdhc Medical Research Services
🇺🇸
Phoenix, Arizona, United States
California Institute of Renal Research
🇺🇸
San Diego, California, United States
Renaissance Renal Research Institute, LLC
🇺🇸
Detroit, Michigan, United States
The Ohio State University
🇺🇸
Columbus, Ohio, United States
Nephrology Associates, P.C.
🇺🇸
Nashville, Tennessee, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Sanford Research/USD-Fargo
🇺🇸
Fargo, North Dakota, United States
Georgia Regents University
🇺🇸
Augusta, Georgia, United States
Illinois Kidney Disease & Hypertension Center
🇺🇸
Peoria, Illinois, United States
Tucson Vascular Consultants
🇺🇸
Tucson, Arizona, United States
Kaiser Permanente Northwest
🇺🇸
Milwaukie, Oregon, United States
Sierra Nevada Nephrology Consultants
🇺🇸
Reno, Nevada, United States
United Health Services
🇺🇸
Johnson City, New York, United States
The Regents University of California Los Angeles
🇺🇸
Los Angeles, California, United States
VA Long Beach Health Care System Pharmacy
🇺🇸
Long Beach, California, United States
Providence Hospital, Research Dept.
🇺🇸
Southfield, Michigan, United States
Wenatchee Valley Medical Center
🇺🇸
Wenatchee, Washington, United States
Toledo Hospital
🇺🇸
Toledo, Ohio, United States
Clinical Research Consultants, LLC
🇺🇸
Kansas City, Missouri, United States
University of California, San Francisco
🇺🇸
San Francisco, California, United States
Metrolina Nephrology Associates, PA
🇺🇸
Charlotte, North Carolina, United States
Temple University School of Medicine
🇺🇸
Philadelphia, Pennsylvania, United States
University of Colorado Denver
🇺🇸
Aurora, Colorado, United States
Tampa General Hospital
🇺🇸
Tampa, Florida, United States
Northwest Renal Clinic, Inc.
🇺🇸
Portland, Oregon, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States