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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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<

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 Summary:
Sponsor: Shire

Current Primary Outcome: 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 [ Time Frame: 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.


Original Primary Outcome: To compare the time to arteriovenous fistula maturation for arteriovenous fistulas treated with SRM003 with those treated with participating sites' standard practice. [ Time Frame: Up to 26 weeks ]

Current Secondary Outcome:

  • Percentage of Participants With AVF Maturation by Week 26 Visit Based on Hemodialysis or CDUS And Vascular Access Examination [ Time Frame: 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 [ Time Frame: 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 Unassisted Primary Patency [ Time Frame: 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 Loss of Assisted Primary Patency [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • Percentage of Participants With Clinical Success Based on First Use of The Study AVF For Hemodialysis [ Time Frame: 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.
  • Number of Interventions to Establish, Maintain, or Restore Patency [ Time Frame: 12 and 26 weeks after surgery ]
    The total number of interventions to establish, maintain, or restore patency was recorded for each participant.


Original Secondary Outcome: To compare the overall duration of patency for AVFs treated with SRM003 with that for AVFs treated with participating sites' standard practice. [ Time Frame: Up to 26 weeks ]

Information By: Shire

Dates:
Date Received: March 5, 2013
Date Started: March 2013
Date Completion:
Last Updated: November 20, 2015
Last Verified: November 2015