Stenosis of Vascular Prosthetic Devices, Implants and Grafts
Conditions
Keywords
Hemodialysis, Vascular Prosthesis, Stenosis, End-stage Renal Disease (ESRD)
Brief summary
The purpose of this study is to confirm the long-term safety and effectiveness of the FLAIR Endovascular Stent Graft for treatment of stenoses at the venous anastomosis of ePTFE or other synthetic arteriovenous (AV) access grafts.
Detailed description
The purpose of the study is to compare efficacy data on subjects randomized to treatment with percutaneous transluminal angioplasty (PTA) and the FLAIR™ Endovascular Stent Graft versus subjects randomized to treatment with PTA only.
Interventions
Treatment of stenoses with primary PTA and placement of the FLAIR Endovascular Stent Graft
PROCEDUREPTA
Treatment of stenoses with PTA only
Sponsors
C. R. Bard
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject must be either a male or non-pregnant female greater than or equal to 21 years of age * Subject is willing to comply with the protocol requirements and can be contacted by telephone * Subject has a synthetic AV access graft located in an arm that has been implanted for greater than or equal to 30 days and has undergone at least one successful dialysis session prior to the index procedure * Angiographic evidence (per the institution's standard) is available to indicate that the subject has a stenosis greater than or equal to 50% located at the graft-vein anastomosis of subject's synthetic AV access graft * The target lesion is estimated to be less than or equal to 7 cm in length (by angiography) * The entire target lesion is located within 7 cm of the graft-vein anastomosis, as verified by angiography, such that approximately 1 cm of the FLAIR™ Endovascular Stent Graft will extend into non-diseased vein and approximately 1 cm but no more than 2 cm of the FLAIR™ Endovascular Stent Graft will extend into the non-diseased AV graft * Full expansion of an appropriately sized angioplasty balloon, in the operator's judgment, can be achieved during primary angioplasty * Graft diameter at the deployment site is between 5 mm and 8 mm as verified by angiography
Exclusion criteria
* The subject has a life expectancy of \< 25 months. * The target lesion has had a corresponding thrombosis treated less than or equal to 7 days prior to the index procedure. * A previously placed stent and/or stent graft located in the treatment area is present. Treatment area includes the entire target lesion and 1 cm of landing zone into both non-diseased AV graft and non-diseased vein. * The subject has an infected AV access graft or uncontrolled systemic infection. * The presence of additional lesion(s) in the access circuit less than or equal to 3 cm from the edges of the target lesion that was treated less than or equal to 30 days prior to index procedure. * The presence of additional lesion(s) in the access circuit \> 3 cm from the edges of the primary lesion that are greater than or equal to 30% stenosed. Note: Subjects may be included if the additional lesions(s) can be successfully treated with a final residual stenosis of \< 30% prior to the index procedure. * The location of the target lesion would require that the FLAIR™ Endovascular Stent Graft be deployed fully across the elbow joint (radiographically identified by a combination of the humeroulnar joint and the humeroradial joint). * The location of the target lesion would require that the FLAIR™ Endovascular Stent Graft cross an angle (between the inflow vein and synthetic AV access graft) that is \> 90 degrees. * The subject has an uncontrolled blood coagulation disorder. * The subject has a known allergy or sensitivity to contrast media which cannot be adequately pre-medicated. * The subject has a known hypersensitivity to nickel-titanium. * Subjects who are currently enrolled or who plan to enroll in other investigations that conflict with follow-up testing or confounds data in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ACPP Was Defined as the Interval Following the Index Procedure Until the Next Access Thrombosis or Reintervention. | 12 months | To demonstrate that the post intervention Access Circuit Primary Patency (ACPP) of FLAIR™ is superior to that of PTA at 12 months post study procedure. |
| The Index of Patency Function (IPF) [the Average Number of Months Between Interventions] of FLAIR™ is Not Inferior to That of PTA at 12 Months Post Study Procedure. | 12 months | The IPF is summarized was defined as the time from the index study procedure to complete graft abandonment divided by the number of visits for a reintervention performed on the arteriovenous (AV) access circuit in order to maintain vascular access for hemodialysis. |
| The Number of Participants With Device and/or Procedure Related Adverse Events at 12 Months Post Study Procedure. | 12 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Procedural Success | Patient Follow-Up | Procedural success was a secondary endpoint without hypothesis testing and is therefore summarized descriptively. Procedural success is defined as anatomic success and at least one indicator of hemodynamic or clinical success. |
| Analysis of Proportion of Serious Adverse Events Classified as Device and/or Procedure-Related Through 30 Days Post-Procedure | Patient Follow-Up | The incidence of device-related and procedure-related serious adverse events (SAEs) from the index procedure through 30 days post procedure is summarized. The purpose of this analysis was to assess the effectiveness of the Bard Peripheral Vascular (BPV) clinician training program. |
| Demonstrate Non-inferiority of FLAIR Safety in Terms of Serious Adverse Events at 12 Months | 12 months | Serious Adverse Events at 12 months are reported for all 270 subjects. |
| Access Circuit Primary Patency (ACCP) at 24 Months Procedure Until the Next Access Thrombosis or Reintervention. | 24 months | Access Circuit Primary Patency (ACPP) was defined as the interval following the index procedure until the next access thrombosis or reintervention at 24 months. |
| To Estimate Safety at 24 Months. | 24 months | To estimate the percentage of participants without safety issues through 24 months. |
| To Assess the Number of Re-interventions to the Access Circuit Until Graft Abandonment or Through 12 Months Post-index Procedure | Patient Follow-Up | The estimated number of re-interventions to the access circuit until graft abandonment or through 12 months post-index procedure was a secondary endpoint without hypothesis testing and is therefore summarized descriptively. |
| Post-intervention Secondary Patency at 24 Months | 24 months | Postintervention secondary patency \[PSP; referred to as Access Circuit Cumulative Patency (ACCP) in the pivotal trial\] was the interval following the treatment procedure until the access circuit was surgically declotted, revised, or abandoned because of inability to treat the original stenosis. |
| Index of Patency Function (IPF) [the Average Number of Months Between Interventions] Rates of FLAIR™ and PTA at at 24 Months. | 24 months | The IPF is summarized was defined as the time from the index study procedure to complete graft abandonment divided by the number of visits for a reintervention performed on the AV access circuit in order to maintain vascular access for hemodialysis. |
| Post-Intervention Assisted Primary Patency at 6 Months | 6 month follow up | Postintervention assisted primary patency (PAPP) was defined as the interval after the index/study procedure until access thrombosis or a surgical intervention that excluded the treated lesion from the access circuit. |
| Post-intervention Secondary Patency at 6 Months | 6 month follow-up | Postintervention secondary patency \[PSP; referred to as Access Circuit Cumulative Patency (ACCP) in the pivotal trial\] was the interval following the treatment procedure until the access circuit was surgically declotted, revised, or abandoned because of inability to treat the original stenosis. |
| Post-Intervention Assisted Primary Patency at 24 Months | 24 month follow up | Postintervention assisted primary patency (PAPP) was defined as the interval after the index/study procedure until access thrombosis or a surgical intervention that excluded the treated lesion from the access circuit. |
| Post-Intervention Assisted Primary Patency at 12 Months | 12 months | Postintervention assisted primary patency (PAPP) was defined as the interval after the index/study procedure until access thrombosis or a surgical intervention that excluded the treated lesion from the access circuit. |
| Post-intervention Secondary Patency (PSP) at 12 Months | 12 months | Postintervention secondary patency \[PSP; referred to as Access Circuit Cumulative Patency (ACCP) in the pivotal trial\] was the interval following the treatment procedure until the access circuit was surgically declotted, revised, or abandoned because of inability to treat the original stenosis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FLAIR FLAIR Endovascular Stent Graft
FLAIR Endovascular Stent Graft: Treatment of stenoses with primary PTA and placement of the FLAIR Endovascular Stent Graft | 138 |
| PTA Only Percutaneous Transluminal Angioplasty
PTA: Treatment of stenoses with PTA only | 132 |
| Total | 270 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Experience | 1 | 0 |
| Overall Study | Death | 37 | 36 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | FLAIR | PTA Only | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 73 Participants | 63 Participants | 136 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 69 Participants | 134 Participants |
| Age, Continuous | 64 years | 63 years | 63.5 years |
| Region of Enrollment United States | 138 participants | 132 participants | 270 participants |
| Sex: Female, Male Female | 87 Participants | 86 Participants | 173 Participants |
| Sex: Female, Male Male | 51 Participants | 46 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 128 / 138 | 127 / 132 |
| serious Total, serious adverse events | 84 / 138 | 87 / 132 |
Outcome results
Primary
ACPP Was Defined as the Interval Following the Index Procedure Until the Next Access Thrombosis or Reintervention.
To demonstrate that the post intervention Access Circuit Primary Patency (ACPP) of FLAIR™ is superior to that of PTA at 12 months post study procedure.
Time frame: 12 months
Population: All patients who were enrolled in the study were included in the analysis in the treatment group to which they were randomized, regardless of the intervention that they actually incurred (an intent-to-treat analysis).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | ACPP Was Defined as the Interval Following the Index Procedure Until the Next Access Thrombosis or Reintervention. | 0.240 proportion of participants |
| PTA Only | ACPP Was Defined as the Interval Following the Index Procedure Until the Next Access Thrombosis or Reintervention. | 0.110 proportion of participants |
Primary
The Index of Patency Function (IPF) [the Average Number of Months Between Interventions] of FLAIR™ is Not Inferior to That of PTA at 12 Months Post Study Procedure.
The IPF is summarized was defined as the time from the index study procedure to complete graft abandonment divided by the number of visits for a reintervention performed on the arteriovenous (AV) access circuit in order to maintain vascular access for hemodialysis.
Time frame: 12 months
Population: All patients who were enrolled in the study will participate in the analysis in the treatment group to which they were randomized, regardless of the intervention that they actually incurred (an intent-to-treat analysis).Blackwelder t-test testing non-inferiority of the FLAIR® group to that of PTA.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FLAIR | The Index of Patency Function (IPF) [the Average Number of Months Between Interventions] of FLAIR™ is Not Inferior to That of PTA at 12 Months Post Study Procedure. | 5.2 Months/intervention | Standard Deviation 4.08 |
| PTA Only | The Index of Patency Function (IPF) [the Average Number of Months Between Interventions] of FLAIR™ is Not Inferior to That of PTA at 12 Months Post Study Procedure. | 4.4 Months/intervention | Standard Deviation 3.51 |
Primary
The Number of Participants With Device and/or Procedure Related Adverse Events at 12 Months Post Study Procedure.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | The Number of Participants With Device and/or Procedure Related Adverse Events at 12 Months Post Study Procedure. | 128 Number of Participants with Device and/o |
| PTA Only | The Number of Participants With Device and/or Procedure Related Adverse Events at 12 Months Post Study Procedure. | 130 Number of Participants with Device and/o |
Secondary
Access Circuit Primary Patency (ACCP) at 24 Months Procedure Until the Next Access Thrombosis or Reintervention.
Access Circuit Primary Patency (ACPP) was defined as the interval following the index procedure until the next access thrombosis or reintervention at 24 months.
Time frame: 24 months
Population: All patients who were enrolled in the study were included in the analysis in the treatment group to which they were randomized, regardless of the intervention that they actually incurred (an intent-to-treat analysis).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Access Circuit Primary Patency (ACCP) at 24 Months Procedure Until the Next Access Thrombosis or Reintervention. | 0.095 proportion of participants |
| PTA Only | Access Circuit Primary Patency (ACCP) at 24 Months Procedure Until the Next Access Thrombosis or Reintervention. | 0.055 proportion of participants |
Secondary
Analysis of Proportion of Serious Adverse Events Classified as Device and/or Procedure-Related Through 30 Days Post-Procedure
The incidence of device-related and procedure-related serious adverse events (SAEs) from the index procedure through 30 days post procedure is summarized. The purpose of this analysis was to assess the effectiveness of the Bard Peripheral Vascular (BPV) clinician training program.
Time frame: Patient Follow-Up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Analysis of Proportion of Serious Adverse Events Classified as Device and/or Procedure-Related Through 30 Days Post-Procedure | 2 events |
| PTA Only | Analysis of Proportion of Serious Adverse Events Classified as Device and/or Procedure-Related Through 30 Days Post-Procedure | 0 events |
Secondary
Demonstrate Non-inferiority of FLAIR Safety in Terms of Serious Adverse Events at 12 Months
Serious Adverse Events at 12 months are reported for all 270 subjects.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Demonstrate Non-inferiority of FLAIR Safety in Terms of Serious Adverse Events at 12 Months | 60.9 percentage of participants with serious |
| PTA Only | Demonstrate Non-inferiority of FLAIR Safety in Terms of Serious Adverse Events at 12 Months | 65.9 percentage of participants with serious |
p-value: 0.449Fisher Exact
Secondary
Index of Patency Function (IPF) [the Average Number of Months Between Interventions] Rates of FLAIR™ and PTA at at 24 Months.
The IPF is summarized was defined as the time from the index study procedure to complete graft abandonment divided by the number of visits for a reintervention performed on the AV access circuit in order to maintain vascular access for hemodialysis.
Time frame: 24 months
Population: All patients who were enrolled in the study will participate in the analysis in the treatment group to which they were randomized, regardless of the intervention that they actually incurred (an intent-to-treat analysis).Blackwelder t-test testing non-inferiority of the FLAIR® group to that of PTA.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FLAIR | Index of Patency Function (IPF) [the Average Number of Months Between Interventions] Rates of FLAIR™ and PTA at at 24 Months. | 7.1 Months/intervention | Standard Deviation 7.04 |
| PTA Only | Index of Patency Function (IPF) [the Average Number of Months Between Interventions] Rates of FLAIR™ and PTA at at 24 Months. | 5.3 Months/intervention | Standard Deviation 5.22 |
Secondary
Post-Intervention Assisted Primary Patency at 12 Months
Postintervention assisted primary patency (PAPP) was defined as the interval after the index/study procedure until access thrombosis or a surgical intervention that excluded the treated lesion from the access circuit.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Post-Intervention Assisted Primary Patency at 12 Months | 0.497 proportion of participants |
| PTA Only | Post-Intervention Assisted Primary Patency at 12 Months | 0.563 proportion of participants |
Secondary
Post-Intervention Assisted Primary Patency at 24 Months
Postintervention assisted primary patency (PAPP) was defined as the interval after the index/study procedure until access thrombosis or a surgical intervention that excluded the treated lesion from the access circuit.
Time frame: 24 month follow up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Post-Intervention Assisted Primary Patency at 24 Months | 0.384 proportion of participants |
| PTA Only | Post-Intervention Assisted Primary Patency at 24 Months | 0.406 proportion of participants |
Secondary
Post-Intervention Assisted Primary Patency at 6 Months
Postintervention assisted primary patency (PAPP) was defined as the interval after the index/study procedure until access thrombosis or a surgical intervention that excluded the treated lesion from the access circuit.
Time frame: 6 month follow up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Post-Intervention Assisted Primary Patency at 6 Months | 0.596 proportion of participants |
| PTA Only | Post-Intervention Assisted Primary Patency at 6 Months | 0.656 proportion of participants |
Secondary
Post-intervention Secondary Patency at 24 Months
Postintervention secondary patency \[PSP; referred to as Access Circuit Cumulative Patency (ACCP) in the pivotal trial\] was the interval following the treatment procedure until the access circuit was surgically declotted, revised, or abandoned because of inability to treat the original stenosis.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Post-intervention Secondary Patency at 24 Months | 0.518 proportion of participants |
| PTA Only | Post-intervention Secondary Patency at 24 Months | 0.574 proportion of participants |
Secondary
Post-intervention Secondary Patency at 6 Months
Postintervention secondary patency \[PSP; referred to as Access Circuit Cumulative Patency (ACCP) in the pivotal trial\] was the interval following the treatment procedure until the access circuit was surgically declotted, revised, or abandoned because of inability to treat the original stenosis.
Time frame: 6 month follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Post-intervention Secondary Patency at 6 Months | 0.748 proportion of participants |
| PTA Only | Post-intervention Secondary Patency at 6 Months | 0.793 proportion of participants |
Secondary
Post-intervention Secondary Patency (PSP) at 12 Months
Postintervention secondary patency \[PSP; referred to as Access Circuit Cumulative Patency (ACCP) in the pivotal trial\] was the interval following the treatment procedure until the access circuit was surgically declotted, revised, or abandoned because of inability to treat the original stenosis.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Post-intervention Secondary Patency (PSP) at 12 Months | 0.653 proportion of participants |
| PTA Only | Post-intervention Secondary Patency (PSP) at 12 Months | 0.710 proportion of participants |
Secondary
Procedural Success
Procedural success was a secondary endpoint without hypothesis testing and is therefore summarized descriptively. Procedural success is defined as anatomic success and at least one indicator of hemodynamic or clinical success.
Time frame: Patient Follow-Up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Procedural Success | 81.2 Percentage of Participants |
| PTA Only | Procedural Success | 75.0 Percentage of Participants |
Secondary
To Assess the Number of Re-interventions to the Access Circuit Until Graft Abandonment or Through 12 Months Post-index Procedure
The estimated number of re-interventions to the access circuit until graft abandonment or through 12 months post-index procedure was a secondary endpoint without hypothesis testing and is therefore summarized descriptively.
Time frame: Patient Follow-Up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FLAIR | To Assess the Number of Re-interventions to the Access Circuit Until Graft Abandonment or Through 12 Months Post-index Procedure | 1.9 reinterventions | Standard Deviation 2.18 |
| PTA Only | To Assess the Number of Re-interventions to the Access Circuit Until Graft Abandonment or Through 12 Months Post-index Procedure | 2.4 reinterventions | Standard Deviation 2.31 |
Secondary
To Estimate Safety at 24 Months.
To estimate the percentage of participants without safety issues through 24 months.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | To Estimate Safety at 24 Months. | 10.9 percentage of participants |
| PTA Only | To Estimate Safety at 24 Months. | 3 percentage of participants |
Post Hoc
Treatment Area Primary Patency (TAPP) at 12 Months.
TAPP is defined as patency (open to blood flow) after the study index procedure until reintervention in the treatment area (within 5mm proximal or 5mm distal to the study device or index balloon angioplasty treated area), or thrombotic occlusion that involved the treatment area.
Time frame: 12 months follow up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Treatment Area Primary Patency (TAPP) at 12 Months. | 0.476 proportion of participants |
| PTA Only | Treatment Area Primary Patency (TAPP) at 12 Months. | 0.248 proportion of participants |
Post Hoc
Treatment Area Primary Patency (TAPP) at 24 Months.
TAPP is defined as patency (open to blood flow) after the study index procedure until reintervention in the treatment area (within 5mm proximal or 5mm distal to the study device or index balloon angioplasty treated area), or thrombotic occlusion that involved the treatment area.
Time frame: 24 months follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FLAIR | Treatment Area Primary Patency (TAPP) at 24 Months. | 0.269 proportion of participants |
| PTA Only | Treatment Area Primary Patency (TAPP) at 24 Months. | 0.135 proportion of participants |