Arteriovenous Graft
Conditions
Keywords
Vascular Injury, Arteriovenous Graft Surgery, Hemodialysis Access
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.
Interventions
BIOLOGICALSRM003
One time implant (3 SRM003 pieces) on surgery day.
Subjects will receive sites' standard practice treatment during the surgical procedure
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participating Site's Standard Practice Participants received the site's standard practice treatment during the surgical procedure. Post-surgery, each participant was to undergo 78 weeks of follow-up for assessment of efficacy and safety. | 14 |
| SRM003 Participants received a single application of 3 sponges at the time of the AVG placement: 1 sponge was wrapped around the venous anastomosis; another sponge was placed longitudinally on the vein segment, immediately distal to the venous anastomosis; and the remaining sponge was wrapped around the arterial anastomosis. Subjects were not permitted to undergo additional applications with SRM003 sponges after the initial application. After surgery, subjects were to undergo assessments during the 78-week follow-up period. | 18 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Other unspecified | 1 | 0 |
| Overall Study | Study terminated by sponsor | 9 | 14 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Participating Site's Standard Practice | SRM003 | Total |
|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 10 | 60.9 years STANDARD_DEVIATION 7.9 | 61.7 years STANDARD_DEVIATION 8.8 |
| Age, Customized <65 years | 9 Participants | 12 Participants | 21 Participants |
| Age, Customized ≥65 years | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 18 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 14 | 17 / 18 |
| serious Total, serious adverse events | 10 / 14 | 10 / 18 |
Outcome results
Primary
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.
Time frame: Up to 78 weeks after surgery
Population: The Intent to-Treat (ITT) population, defined as all randomly assigned participants regardless of the treatment received or having post-baseline outcome data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participating Site's Standard Practice | Percentage of Participants With Loss of Unassisted Primary Patency | 35.7 percentage of participants |
| SRM003 | Percentage of Participants With Loss of Unassisted Primary Patency | 66.7 percentage of participants |
Comparison: Analysis of time to loss of patencyp-value: 0.138Log Rank
Secondary
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.
Time frame: 26 weeks after surgery
Population: The ITT population, defined as all randomly assigned participants regardless of the treatment received or having post-baseline outcome data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participating Site's Standard Practice | Number of Interventions to Establish, Maintain, or Restore Patency | 0.7 interventions | Standard Deviation 2.16 |
| SRM003 | Number of Interventions to Establish, Maintain, or Restore Patency | 0.9 interventions | Standard Deviation 1 |
95% CI: [-0.942, 1.402]
Secondary
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.
Time frame: Up to 78 weeks after surgery
Population: The ITT population, defined as all randomly assigned participants regardless of the treatment received or having post-baseline outcome data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participating Site's Standard Practice | Percentage of Participants With Loss of Assisted Primary Patency | 28.6 percentage of participants |
| SRM003 | Percentage of Participants With Loss of Assisted Primary Patency | 55.6 percentage of participants |
Comparison: Analysis of time to loss of patencyp-value: 0.312Log Rank
Secondary
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.
Time frame: Up to 78 weeks after surgery
Population: The ITT population, defined as all randomly assigned participants regardless of the treatment received or having post-baseline outcome data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participating Site's Standard Practice | Percentage of Participants With Loss of Secondary Patency | 7.1 percentage of participants |
| SRM003 | Percentage of Participants With Loss of Secondary Patency | 27.8 percentage of participants |
Comparison: Analysis of time to loss of patencyp-value: 0.093Log Rank