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

• SRM003 (Biological), also known as Allogeneic human aortic endothelial cells cultured in a gelatin matrix (Gelfoam®).: One time implant (3 SRM003 pieces) on surgery day.
• Participating Site's standard practice (Other): Subjects will receive sites' standard practice treatment during the surgical procedure

Primary outcomes

• Percentage of Participants With Loss of Unassisted Primary Patency [Up to 78 weeks after surgery]: 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.

Secondary outcomes

• Percentage of Participants With Loss of Assisted Primary Patency [Up to 78 weeks after surgery]: 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.
• Percentage of Participants With Loss of Secondary Patency [Up to 78 weeks after surgery]: 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.
• Number of Interventions to Establish, Maintain, or Restore Patency [26 weeks after surgery]: The total numbers of interventions to establish, maintain, or restore patency was assessed at the Week 26 visit.

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Percentage of Participants With Loss of Unassisted Primary Patency (Primary), Number, percentage of participants: Participating Site's Standard Practice 35.7; SRM003 66.7 (p 0.138)
• Percentage of Participants With Loss of Assisted Primary Patency (Secondary), Number, percentage of participants: Participating Site's Standard Practice 28.6; SRM003 55.6 (p 0.312)
• Percentage of Participants With Loss of Secondary Patency (Secondary), Number, percentage of participants: Participating Site's Standard Practice 7.1; SRM003 27.8 (p 0.093)
• Number of Interventions to Establish, Maintain, or Restore Patency (Secondary), Mean, interventions: Participating Site's Standard Practice 0.7 +/- 2.16; SRM003 0.9 +/- 1.00

Adverse events

Serious adverse events by term

Other adverse events by term

32 more terms not shown.

Limitations and caveats: Study was discontinued early due to Sponsor decision.

• Study Director, Study director, Takeda