Hypertension, Renal, Renal Artery Obstruction
Conditions
Brief summary
The purpose of this study is to determine whether the Herculink Elite Renal Stent System is safe and effective in the treatment of renal artery stenosis in patients with less than optimal angioplasty results and uncontrolled hypertension. CAUTION: The Herculink Elite Renal Stent System Is An Investigational Device. Limited by Federal (U.S.) Law to Investigational Use Only.
Detailed description
To evaluate the safety and effectiveness of the RX Herculink Elite Renal Stent System in the treatment of suboptimal post-procedural percutaneous transluminal angioplasty (PTA) of atherosclerotic de novo or restenotic renal artery stenosis in patients with uncontrolled hypertension. CAUTION: The Herculink Elite Renal Stent System Is An Investigational Device. Limited by Federal (U.S.) Law to Investigational Use Only.
Interventions
DEVICEHerculink Elite Renal Stent System
This is a prospective, non-randomized, single arm, multi-center study to evaluate the safety and effectiveness of the RX Herculink Elite Renal Stent System in patients with sub-optimal renal PTA results in de novo or restenotic renal artery lesions. Patients who satisfy the inclusion/exclusion criteria will be enrolled at sites in the United States. Patients will have follow up visits for evaluation.
Sponsors
Abbott Medical Devices
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Clinical Inclusion Criteria: * Subject is ≥18 years of age. * Subject and subject's physician agree to have the subject return for all required contact following study enrollment. * Subject has been informed of the nature of the study, and has provided written informed consent, approved by the appropriate Institutional Review Board (IRB) of the respective clinical site. * Subject is a candidate for renal artery stenting. * Subject has uncontrolled systolic hypertension (systolic Blood Pressure\[SBP\] ≥140 mmHg), or uncontrolled diastolic hypertension (diastolic BP \[DBP\] ≥90 mmHg), or a combination of both in the presence of at least two (2) or more antihypertensive medications. * Subject has a baseline serum Creatinine of \<2.5mg/dl Angiographic Inclusion Criteria * Subject has either unilateral or bilateral de novo or restenotic after Percutaneous Transluminal Angioplasty (PTA) (in-stent restenosis excluded) atherosclerotic lesion(s). If bilateral lesions are to be treated, the most severe lesion must be successfully treated without complications before progressing to treat the second lesion. Treatment of bilateral lesions is to occur in the same procedural event. * Renal stenosis must be visually estimated to be ≥60% by angiography. * Subject has a suboptimal PTA result, defined as one of the following: * ≥50% residual stenosis * 10 mm Hg mean gradient or 20 mm Hg peak systolic gradient across the target lesion * A flow-limiting dissection (NHLBI grade D) or TIMI flow \<3 * Renal stenosis must be visually estimated to be within 10 mm of the aortic renal border by angiography. * Target vessel reference diameter must be visually estimated to be ≥4mm and ≤7mm by angiography * Target lesion length must be visually estimated to be ≤15mm (including dissection) by angiography. * Expected ability to deliver the stent to the lesion (absence of excessive tortuosity or calcification). * Expected ability to fully expand the stent. Clinical
Exclusion criteria
* Subject has known hypersensitivity or contraindication to cobalt chromium or standard intraprocedure anticoagulant(s); subject has sensitivity to contrast which cannot be adequately pre-treated with medication. * Subject has known allergy or contraindication to clopidogrel (Plavix) or aspirin. * Subject has known bleeding disorder or hypercoagulable disorder, or will refuse blood transfusions. * Subject has suffered a gastrointestinal (GI) bleed within 30 days before the index procedure that would interfere with antiplatelet therapy. * Subject has renal insufficiency defined as serum Creatinine \>2.5 mg/dl. * Subject has any immunosuppressive disorder, access site infection, or acute systemic infection due to any cause. * Subject has other medical illnesses (e.g., cancer, end-stage congestive heart failure) that may cause the subject to be non-compliant with protocol requirements, confound the data interpretation, or is associated with a life expectancy of less than three years. * Subject has any medical illnesses that would make them unlikely to respond to treatment (e.g., sickle cell nephropathy/sickle cell disease, scleroderma, arteriolar nephrosclerosis, hemolytic-uremic syndrome and vasculitis). * Subject has had a Q-wave MI within 30 days before index procedure. * Subject has had a stroke or TIA within 30 days before index procedure. * Subject has a history of congestive heart failure and has a previously documented LVEF ≤25%. * Subject is normotensive or has adequate control of hypertension (SBP \<140 mmHg and DBP \<90 mm Hg) utilizing diet control and/or medication regimen involving only one antihypertensive medication. * Subject has acute thrombophlebitis or deep vein thrombosis. * Subject is actively participating in another drug or device trial and has not completed the required protocol follow-up period. Subject may be enrolled only once in this study (Protocol # 05-102) and may not participate in any other clinical trial during the follow-up period. * Subject is unable to understand and cooperate with study procedures or provide informed consent. * Subject is unable to return for follow-up visits (distance, etc). * Subject is pregnant. * Subject has undergone vascular surgery (CABG, AAA repair, AF bypass) and has not fully recovered from the effects of surgery (\<3 months). * Subject has planned staged treatment of bilateral renal artery stenosis. * Subject has had prior surgical intervention to the target artery, or has undergone previous stent placement in the target lesion. * Target lesion is located in a transplanted kidney. * Kidney to be treated is \<8 cm as determined by duplex ultrasound report, CTA report, or MRA report within 180 days before procedure. If kidney size is documented by more than one method, e.g. CTA and ultrasound, and one of the methods is duplex ultrasound, the kidney size as documented by duplex ultrasound shall be used to determine study eligibility. * Subject has planned additional ancillary procedure(s) during renal stenting procedure. Angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Binary Restenosis Rate | 9 months | Determined by duplex ultrasound or angiogram. Reported as the percentage of participants with occurance of binary restenosis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ipsilateral Nephrectomy | 30 days | Ipsilateral: Situated on or affecting the same side as treated. Nephrectomy: Removal of the affected kidney |
| Embolic Events Resulting in Kidney Damage | 30 days | Percentage of participants with an embolic event resulting in kidney damage. |
| Event Free Rate of Clinically Indicated Target Lesion Revascularization (TLR) | 9 months | Event Free percentage: Defined as percentage of participants free from this event. |
| 9 Month Blood Pressure (Systolic) | Baseline (Pre-Procedure) and 9 months | As compared to baseline (pre-procedure). Blood pressure measurements at 9 months. |
| 9 Month Blood Pressure (Diastolic) | 9 months and baseline | As compared to baseline. See Population description. |
| Acute Device Success | From beginning of index procedure to end of index proceedure. | Acute device success is defined as, on a per device basis, the achievement of successful delivery of the assigned device(s)as intended to the designated location. |
| Acute Procedure Success | From beginning of index proceedure to end of index proceedure. | Attainment of a final result of \< 30% residual stenosis, as determined by the Angiographic Core Lab. |
| Death for Any Reason | 30 days | — |
| Primary Patency | 9 months | Defined as \<60% stenosis without prior re-intervention, as determined by duplex ultrasound or angiogram. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. |
| Secondary Patency Rate of <60% Stenosis of the Target Lesion | 9 months | As determined by duplex ultrasound or angiography regardless of PTA, stenting, or bypass since index procedure. Rate reported as a percentage of participants with this condition. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. |
| 9 Month Anti-hypertensive Medication In-take, 1 Medication | 9 months | Number of Anti-Hypertensive Medications taken-baseline compared to follow up, Per Subject Analysis (Intent-to-Treat Population), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. |
| 9 Month Anti-hypertensive Medication In-take, 2 Medications | 9 months | Number of Anti-Hypertensive Medications taken-baseline compared to follow up, Per Subject Analysis (Intent-to-Treat Population)), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. |
| 9 Month Anti-hypertensive Medication In-take, 3 Medications | 9 months | Number of Anti-Hypertensive Medications taken-baseline compared to follow up, Per Subject Analysis (Intent-to-Treat Population)), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. |
| 9 mo in Anti-hypertensive Medication In-take, ≥ 4 Medications | 9 months | Number of Anti-Hypertensive Medications taken at follow up compared to baseline, Per Subject Analysis (Intent-to-Treat Population)), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. |
| Renal Function (Measured by sCr) | 9 months | sCR= Serum Creatinine, per subject analysis. ITT. Renal function (measured by sCr) @ baseline: 1.2mg/dL (1.2, 1.3). The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. |
| Acute Clinical Success | From beginning of index proceedure to end of index proceedure. | Procedure success without Major Adverse Events (MAE)or access site event requiring surgical or percutaneous intervention prior to hospital discharge. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. |
Countries
United States
Participant flow
Recruitment details
All subjects admitted for percutaneous renal artery revascularization were considered for enrollment at sites throughout the USA. Dates of enrollment: August 31, 2007 through October 02, 2009.
Pre-assignment details
Subjects required to have documented uncontrolled hypertension (SBP at least 140 mmHg or DBP at least 90 mmHg, or both) in the presence of at least two (2) or more antihypertensive medications, all clinical eligibility criteria had to have been met and sujects had to sign the informed consent form. Intent to treat (ITT) population.
Participants by arm
| Arm | Count |
|---|---|
| RX Herculink Elite To evaluate the safety and effectiveness of the RX Herculink Elite Renal Stent System in the treatment of suboptimal post-procedural percutaneous transluminal angioplasty (PTA) of atherosclerotic de novo or restenotic renal artery stenosis in patients with uncontrolled hypertension. | 202 |
| Total | 202 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | 30 day f/u, only non-study stent used | 3 |
| Overall Study | Death | 5 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | RX Herculink Elite |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 163 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Age Continuous | 72.1 years STANDARD_DEVIATION 9.4 |
| Region of Enrollment United States | 202 participants |
| Sex: Female, Male Female | 126 Participants |
| Sex: Female, Male Male | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 145 / 199 |
| serious Total, serious adverse events | 83 / 199 |
Outcome results
Primary
Binary Restenosis Rate
Determined by duplex ultrasound or angiogram. Reported as the percentage of participants with occurance of binary restenosis.
Time frame: 9 months
Population: Subject total reflects those who were evaluable at the time of analysis. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. Only a certain number of patients were required to have angiographic follow-up to provide this endpoint information.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Binary Restenosis Rate | 10.5 Percentage of lesions |
Comparison: objective is to demonstrate the binary restenosis rate at 9 months is \< 28.6% OPC. Assumptions for the primary endpoint analysis:~* H0: Restenosis Rate ≥ 28.6%~* HA: Restenosis Rate \< 28.6%~* Assumed binary restenosis rate = 20%~* Power = 80%~* One-sided type I error = 5%~With the above assumptions, 161 samples would be required. To account for approximately 20% lost to follow-up rate, 202 subjects will be enrolled in the study. The sample size calculation was performed using PASS 2005.p-value: <0.00011-sided exact binomial test
Secondary
9 mo in Anti-hypertensive Medication In-take, ≥ 4 Medications
Number of Anti-Hypertensive Medications taken at follow up compared to baseline, Per Subject Analysis (Intent-to-Treat Population)), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
Time frame: 9 months
Population: Patients with baseline Anti-Hypertensive medication intake equal to or greater than 4 Medications: 39.6%
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | 9 mo in Anti-hypertensive Medication In-take, ≥ 4 Medications | 37.4 percentage of participants |
Secondary
9 Month Anti-hypertensive Medication In-take, 1 Medication
Number of Anti-Hypertensive Medications taken-baseline compared to follow up, Per Subject Analysis (Intent-to-Treat Population), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
Time frame: 9 months
Population: Patients with baseline Anti-Hypertensive medication intake equal to 1 medication: 0.5%
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | 9 Month Anti-hypertensive Medication In-take, 1 Medication | 4.6 percentage of participants |
Secondary
9 Month Anti-hypertensive Medication In-take, 2 Medications
Number of Anti-Hypertensive Medications taken-baseline compared to follow up, Per Subject Analysis (Intent-to-Treat Population)), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
Time frame: 9 months
Population: Patients with baseline Anti-Hypertensive medication intake equal to 2 medications: 29.2%
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | 9 Month Anti-hypertensive Medication In-take, 2 Medications | 29.3 percentage of participants |
Secondary
9 Month Anti-hypertensive Medication In-take, 3 Medications
Number of Anti-Hypertensive Medications taken-baseline compared to follow up, Per Subject Analysis (Intent-to-Treat Population)), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
Time frame: 9 months
Population: Patients with baseline Anti-Hypertensive medication intake equal to 3 Medications: 30.7%
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | 9 Month Anti-hypertensive Medication In-take, 3 Medications | 28.2 percentage of participants |
Secondary
9 Month Blood Pressure (Diastolic)
As compared to baseline. See Population description.
Time frame: 9 months and baseline
Population: The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| RX Herculink Elite | 9 Month Blood Pressure (Diastolic) | 9 month Diastolic Blood Pressure | 75.4 mmHg |
| RX Herculink Elite | 9 Month Blood Pressure (Diastolic) | Baseline Diastolic Blood Pressure | 77.7 mmHg |
Secondary
9 Month Blood Pressure (Systolic)
As compared to baseline (pre-procedure). Blood pressure measurements at 9 months.
Time frame: Baseline (Pre-Procedure) and 9 months
Population: The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| RX Herculink Elite | 9 Month Blood Pressure (Systolic) | 9 month Systolic Blood Pressure | 145.3 mmHg |
| RX Herculink Elite | 9 Month Blood Pressure (Systolic) | Baseline (Pre-Procedure) Systolic Blood Pressure | 162.3 mmHg |
Secondary
Acute Clinical Success
Procedure success without Major Adverse Events (MAE)or access site event requiring surgical or percutaneous intervention prior to hospital discharge. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
Time frame: From beginning of index proceedure to end of index proceedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Acute Clinical Success | 98 percentage of participants |
Secondary
Acute Device Success
Acute device success is defined as, on a per device basis, the achievement of successful delivery of the assigned device(s)as intended to the designated location.
Time frame: From beginning of index procedure to end of index proceedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Acute Device Success | 96.0 percentage of devices |
Secondary
Acute Procedure Success
Attainment of a final result of \< 30% residual stenosis, as determined by the Angiographic Core Lab.
Time frame: From beginning of index proceedure to end of index proceedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Acute Procedure Success | 99.2 percentage of participants |
Secondary
Death for Any Reason
Time frame: 30 days
Population: Non-Hierarchical Subject Counts, Per Subject Analysis (Intent-to-Treat Population). The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Death for Any Reason | 0.5 percentage of participants |
Secondary
Embolic Events Resulting in Kidney Damage
Percentage of participants with an embolic event resulting in kidney damage.
Time frame: 30 days
Population: The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Embolic Events Resulting in Kidney Damage | 1.0 Percentage of participants |
Secondary
Event Free Rate of Clinically Indicated Target Lesion Revascularization (TLR)
Event Free percentage: Defined as percentage of participants free from this event.
Time frame: 9 months
Population: The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Event Free Rate of Clinically Indicated Target Lesion Revascularization (TLR) | 96.9 Event Free Percentage |
Secondary
Ipsilateral Nephrectomy
Ipsilateral: Situated on or affecting the same side as treated. Nephrectomy: Removal of the affected kidney
Time frame: 30 days
Population: intention to treat (ITT). The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Ipsilateral Nephrectomy | 0 percentage of participants |
Secondary
Primary Patency
Defined as \<60% stenosis without prior re-intervention, as determined by duplex ultrasound or angiogram. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
Time frame: 9 months
Population: Subject total reflects those who were evaluable at the time of analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Primary Patency | 88 percentage of participants |
Secondary
Renal Function (Measured by sCr)
sCR= Serum Creatinine, per subject analysis. ITT. Renal function (measured by sCr) @ baseline: 1.2mg/dL (1.2, 1.3). The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
Time frame: 9 months
Population: Subject total reflects those who were evaluable at the time of analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX Herculink Elite | Renal Function (Measured by sCr) | 1.3 mg/dL | 95% Confidence Interval 0.6 |
Secondary
Secondary Patency Rate of <60% Stenosis of the Target Lesion
As determined by duplex ultrasound or angiography regardless of PTA, stenting, or bypass since index procedure. Rate reported as a percentage of participants with this condition. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician.
Time frame: 9 months
Population: Subject total reflects those who were evaluable at the time of analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RX Herculink Elite | Secondary Patency Rate of <60% Stenosis of the Target Lesion | 95.2 percentage of participants |