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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Arteriovenous Graft

Intervention / Treatment
-----------------
* Biological: SRM003
* Other: Participating Site's standard practice


Participation Criteria
=================
Eligibility Criteria
-----------------
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 prosthetic expanded polytetrafluoroethylene AVG placed in the upper extremity. Subject must have a life expectancy of at least 78 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 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. Subject has had more than 3 access placement surgeries (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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vascular Injury, Arteriovenous Graft Surgery, Hemodialysis Access