Arteriovenous Fistula, Chronic Kidney Failure, Complication of Hemodialysis, Complication of Renal Dialysis, End Stage Kidney Disease, End Stage Renal Disease, ESRD, Vascular Access Complication
Conditions
Keywords
Dialysis, End Stage Renal Disease, End Stage Kidney Disease, ESRD, Chronic Kidney Failure, Chronic Renal Failure, Chronic Kidney Disease, Hemodialysis, Vascular Access, Arteriovenous Fistula, AV Fistula, AVF, Nephrology, Vascular Surgery, Dialysis Access
Brief summary
The objective of this study is to evaluate efficacy and safety outcomes following use of the Sirolimus-eluting Collagen Implant (SeCI) in subjects undergoing surgical creation of an AV fistula for vascular access (index procedure).
Detailed description
The objective of this study is to evaluate efficacy and safety outcomes following use of the Sirolimus-eluting Collagen Implant (SeCI) in subjects undergoing surgical creation of an AV fistula for vascular access (index procedure). Following successful creation of the AV fistula, the cohort randomized to the treatment group will receive the SeCI; the control group will not receive an implant. The primary hypothesis is that the proportion of subjects that meet requirements for fistula suitability for dialysis six months following the index procedure will be higher in the treatment group in comparison to the control group.
Interventions
DRUGSirolimus
A single dose of sirolimus delivered locally
PROCEDUREAV Fistula Surgery
AV Fistula Surgery
DEVICESirolimus-eluting Collagen Implant (SeCI)
SeCI placed at and around the site of the anastomosis of an AV fistula, immediately following completion of a successful AV fistula surgery.
Sponsors
Vascular Therapies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Currently on hemodialysis for ≤12 months or expected to initiate hemodialysis within approximately 6 months of the creation of the AV fistula. * Vascular anatomy suitable for creation of the AV fistula, determined by pre procedure duplex ultrasound * Successful creation of a single stage radiocephalic or brachiocephalic end to side fistula
Exclusion criteria
* Prior AV access created on the limb where the fistula surgery is planned * ST-elevation MI or cerebrovascular accident within 30 days of the index procedure * Known hypersensitivity to the following: sirolimus, beef or bovine collagen * Hypotension with systolic blood pressures \<100 mm Hg at the time of screening * Known or suspected active infection at the time of the AV fistula surgery * Known to be HIV positive * Prisoner, mentally incompetent, and/or alcohol or drug abuser
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fistula Suitability for Dialysis at 6 Months (FSD6) | 6 months | For subjects who are on hemodialysis by day 150, suitability for dialysis will be determined by the ability to use the fistula for dialysis using 2-needles with a mean dialysis machine blood pump speed of ≥300 mL/min for two-thirds of the dialysis sessions during a 30 day suitability ascertainment period that begins 150 days after fistula creation. For subjects who are not on hemodialysis on day of enrollment and who do not initiate hemodialysis by day 150, suitability for dialysis will be determined by a vascular ultrasound performed at the 6 month follow up visit. Suitability for dialysis will be defined as a fistula with an access vein diameter (AVD) of ≥6 mm (internal diameter) and an access blood flow of ≥500 mL/min. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sirogen Participants received single administration of Sirolimus-eluting Collagen Implant (Sirogen) at the time of AV fistula surgery | 125 |
| Control Participants underwent AV fistula surgery without an implant | 118 |
| Run-in Participants received single administration of Sirolimus-eluting Collagen Implant (Sirogen) at the time of AV fistula surgery. The first subject enrolled by a participating surgeon was a run-in subject; run-in subjects were part of the randomized set; all run-in subjects receive Sirogen. | 26 |
| Total | 269 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Death | 8 | 4 | 2 |
| Overall Study | Lost to Follow-up | 2 | 4 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 7 | 2 |
Baseline characteristics
| Characteristic | Sirogen | Total | Run-in | Control |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 100 Participants | 13 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 74 Participants | 169 Participants | 13 Participants | 82 Participants |
| Age, Continuous | 59.7 years STANDARD_DEVIATION 14.9 | 59.0 years STANDARD_DEVIATION 14.7 | 61.4 years STANDARD_DEVIATION 17.3 | 57.7 years STANDARD_DEVIATION 13.9 |
| Kidney Disease Status at Enrollment Chronic kidney disease | 33 Participants | 70 Participants | 1 Participants | 36 Participants |
| Kidney Disease Status at Enrollment End stage renal disease | 92 Participants | 199 Participants | 25 Participants | 82 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 12 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 69 Participants | 8 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 84 Participants | 180 Participants | 15 Participants | 81 Participants |
| Region of Enrollment United States | 125 participants | 269 participants | 26 participants | 118 participants |
| Sex: Female, Male Female | 28 Participants | 57 Participants | 6 Participants | 23 Participants |
| Sex: Female, Male Male | 97 Participants | 212 Participants | 20 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 127 | 4 / 116 | 2 / 26 |
| other Total, other adverse events | 115 / 127 | 101 / 116 | 24 / 26 |
| serious Total, serious adverse events | 56 / 127 | 55 / 116 | 15 / 26 |
Outcome results
Primary
Fistula Suitability for Dialysis at 6 Months (FSD6)
For subjects who are on hemodialysis by day 150, suitability for dialysis will be determined by the ability to use the fistula for dialysis using 2-needles with a mean dialysis machine blood pump speed of ≥300 mL/min for two-thirds of the dialysis sessions during a 30 day suitability ascertainment period that begins 150 days after fistula creation. For subjects who are not on hemodialysis on day of enrollment and who do not initiate hemodialysis by day 150, suitability for dialysis will be determined by a vascular ultrasound performed at the 6 month follow up visit. Suitability for dialysis will be defined as a fistula with an access vein diameter (AVD) of ≥6 mm (internal diameter) and an access blood flow of ≥500 mL/min.
Time frame: 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sirogen | Fistula Suitability for Dialysis at 6 Months (FSD6) | Met FSD6 criteria | 74 Participants |
| Sirogen | Fistula Suitability for Dialysis at 6 Months (FSD6) | Did not meet FSD6 criteria | 43 Participants |
| Sirogen | Fistula Suitability for Dialysis at 6 Months (FSD6) | Indeterminant FSD6 | 8 Participants |
| Control | Fistula Suitability for Dialysis at 6 Months (FSD6) | Indeterminant FSD6 | 7 Participants |
| Control | Fistula Suitability for Dialysis at 6 Months (FSD6) | Met FSD6 criteria | 76 Participants |
| Control | Fistula Suitability for Dialysis at 6 Months (FSD6) | Did not meet FSD6 criteria | 35 Participants |
| Run-in | Fistula Suitability for Dialysis at 6 Months (FSD6) | Did not meet FSD6 criteria | 5 Participants |
| Run-in | Fistula Suitability for Dialysis at 6 Months (FSD6) | Met FSD6 criteria | 21 Participants |
| Run-in | Fistula Suitability for Dialysis at 6 Months (FSD6) | Indeterminant FSD6 | 0 Participants |
p-value: 0.2942Regression, Logistic