Hypertension, Renovascular, Renal Artery Stenosis
Conditions
Keywords
Renal Artery Stenosis, Renal Artery Obstruction, Renovascular Hypertension, Resistant Hypertension, Renal Revascularization, Atherosclerotic Renal Artery Stenosis, Atherosclerotic Renal Artery Stenosis (ARAS), Renal Artery Stenosis (RAS), Uncontrolled hypertension, Hypertension, Systolic blood pressure, Blood pressure
Brief summary
The purpose of this trial is to test how well the iCAST™ RX Stent works in patients diagnosed with atherosclerotic renal artery stenosis and whether or not increased blood flow by the stent will help to control blood pressure.
Detailed description
This is a prospective, single-arm, multicenter clinical trial that will take place at up to 25 US/ Outside US (OUS) sites. Primary endpoints have been determined to show the safety, effectiveness, and clinical outcomes of the iCAST™ RX Stent System. Safety and effectiveness will be evaluated based on the primary patency rate at 9-months on a per lesion basis evaluated against a performance goal of published studies with bare-metal stents. The primary clinical endpoint will assess the improvement in Systolic Blood Pressure (SBP) at 9-months as compared to baseline Systolic Blood Pressure. Eligible subjects will undergo a two-week Medical Documentation Screening period to confirm resistant hypertension (SBP ≥ 155mmHg) while on maximum tolerable doses of ≥ three anti-hypertensive medications from at least three distinct classes of drugs, one of which must be a diuretic. There must be documented clinical evidence to support likelihood of angiographic findings \> 80% whether it is Duplex Ultrasound (DUS), Computed Tomography angiogram (CTa), Magnetic Resonance angiogram (MRa) or other medical evidence. After meeting screening and clinical eligibility criteria, subjects will undergo a baseline assessment for angiographic eligibility. After angiographic documentation of a ≥ 80% renal artery stenosis or Fraction Flow Reserve (FFR) \< 0.8 is confirmed, the subject may be enrolled in the trial by placement of the investigational device. The 9-month visit will include a follow-up DUS of the target renal artery. If the DUS is non-diagnostic due to an imaging problem, such as overlying bowel gas or body habitus, a second DUS may be attempted. If the DUS is indicative of ≥ 60% stenosis as determined by the core laboratory, or the second DUS remains non-diagnostic, a contrast angiogram will be used to assess the degree of restenosis of the covered stent(s). Clinical follow-up visits will be required for all enrolled subjects at 30-days, 9-months, 12-months, 24-months, and 36-months. A 6-month and 18-month visit will occur via telephone to collect medication usage and Adverse Events (AEs) only. The 36-month clinic office visit will be required as the final safety visit.
Interventions
DEVICEiCAST™ Rx Stent System
All enrolled subjects will undergo primary stenting of the target lesion(s) by placement of the iCAST™ RX Stent System.
Sponsors
Atrium Medical Corporation
Study design
Allocation
NA
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 Inclusion Criteria: 1. Age ≥ 18 at the time of informed consent. 2. Subject or subject's legal representative have been informed of the nature of the trial, agrees to participate, and has signed an Institutional Review Board (IRB)/Ethics Committee (EC) approved Informed Consent Form (ICF). 3. Subjects that have bilateral kidneys or a solitary functioning kidney with Renal Artery Stenosis in at least one kidney and an average Systolic Blood Pressure (SBP) ≥ 155mmHg. 4. Subject has a history of maximum tolerable dose of ≥ 3 anti-hypertensive medications of different classes, one of which must be a diuretic (for at least two weeks prior to Medical Documentation Screening period). a. A documented history for a minimum of 3 months showing reasonable and aggressive efforts to manage hypertension prior to consent. This must include the use of a broad variety of medications that have been used and failed or not tolerated. 5. Subject must have documented clinical evidence to support likelihood of angiographic findings \> 80% whether it is DUS, CTa, MRa or other medical evidence. 6. New York Heart Association (NYHA) class I, II, or III the time of trial enrollment. Note: When a subject has bilateral Renal Artery Stenosis both of which require stenting, it is recommended to treat both kidneys with an iCAST™ RX Stent System during the index procedure. In the event that a subject needs a renal stenting procedure staged for renal protection, it is important that the Investigator treats the second renal artery with an iCAST™ RX Stent System after 30 days of the index procedure. If subjects with bilateral stenosis have only one lesion that meets protocol inclusion criteria that lesion should be treated per protocol. The recommendation is to NOT treat the second non-qualifying lesion, however if the operator feels strongly it is indicated, then they should treat per standard of care after 30-days post index procedure in order to comply with
Exclusion criteria
#10. Subjects with flash pulmonary edema are allowed into the trial should they meet all other Inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Patency | 9 months | Primary patency rate at 9 months was defined as continuous patency without the occurrence of a total occlusion of the original lesion, without a re-intervention to treat a partial or total occlusion of the stented segment, or bypass of the stented segment due to clinically-driven restenosis or occlusion. |
| Systolic Blood Pressure | Baseline and 9 months | Change in systolic blood pressure (SBP) at 9 months as compared to baseline SBP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Procedural Success | Day of Procedure, prior to hospital discharge | Acute procedural success is defined as technical success without the occurrence of MAE prior to hospital discharge. |
| Target Lesion Revascularization (TLR) | 9 months | Target Lesion Revascularization (TLR) is measured as the proportion of subjects-lesions that require a clinically-driven reintervention of the target lesion through 9 months. a. A clinically-driven TLR is defined as a TLR (percutaneous balloon angioplasty (PTA), bare metal stent or repeat covered stent deployment, or surgical bypass) due to documented recurrent hypertension from 30-days post-procedure level and/or deterioration in renal function from baseline value, associated with angiographic core laboratory adjudication of a ≥ 60% diameter covered stent restenosis. |
| Rate of Incidental TLR | 9 months | The rate of incidental TLR is the rate of TLRs not meeting the definition of a clinically-driven TLR. |
| Systolic Blood Pressure (SBP) Control | Baseline and 30 days | The change in SBP from baseline to 30 days |
| Procedure-Related Major Adverse Events (MAE) | 30 days, 9 months | The occurence of procedure-related MAEs is reported as a percentage of subjects with MAE. Inclusive of: 1. Procedure- or device-related occurrence of death 2. Q-Wave myocardial infarction (MI) 3. Clinically driven target lesion revascularization (TLR) 4. Significant embolic events defined as unanticipated kidney/bowel infarct, clinically driven by symptoms of abdominal or back pain and confirmed with CT scan or open surgery; lower extremity ulceration or gangrene; or kidney failure. |
| Secondary Patency Rate | 9 months | Secondary patency rate at 9 months after a clinically-driven TLR which restores patency after total occlusion. |
| Change in Number of Anti-Hypertensive Medications | Baseline and 9 months | Change in number of anti-hypertensive medications as compared to baseline. |
| Change in Renal Function | Baseline and 30 days | Renal function compared to baseline as measured by estimated Glomerular Filtration Rate (eGFR) at 30 days. |
| SBP Control | Baseline and 9 months | The change in SBP from baseline to 9 months |
| Technical Success | Day of Procedure | Technical success is defined as successful delivery and deployment of the iCAST™ RX Stent System with ≤ 30% residual angiographic stenosis after covered stent deployment (including post-dilatation) assessed via quantitative vascular analysis (QVA) by an independent core laboratory. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| iCAST™ RX Stent System All enrolled subjects, defined as patients that underwent primary stenting of the target lesion(s) by placement of the iCAST™ RX Stent System. | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | iCAST™ RX Stent System |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 52 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 71.7 years STANDARD_DEVIATION 10.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of Qualifying Lesions Bilateral | 14 Participants |
| Number of Qualifying Lesions Unilateral | 54 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 53 Participants |
| Region of Enrollment United States | 68 Participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 33 Participants |
| Systolic Blood Pressure | 166.2 mmHg STANDARD_DEVIATION 12.19 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 68 |
| other Total, other adverse events | 12 / 68 |
| serious Total, serious adverse events | 40 / 68 |
Outcome results
Primary
Primary Patency
Primary patency rate at 9 months was defined as continuous patency without the occurrence of a total occlusion of the original lesion, without a re-intervention to treat a partial or total occlusion of the stented segment, or bypass of the stented segment due to clinically-driven restenosis or occlusion.
Time frame: 9 months
Population: Subset of enrolled subjects with available duplex ultrasound or angiography assessment within the 9-month visit window.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| iCAST™ RX Stent System | Primary Patency | 66 Subject-lesions |
Comparison: The original Performance Goal of 70% patency rate was derived from a thorough literature review of trials with renal bare metal stent placement. Other assumptions included a determination of samples size based upon a one-sided alpha of 0.025 and desired power of 87%, and assumption of 10% attrition. The null hypothesis was that the incidence of primary patency at 9 months is less than or equal to 70%.p-value: <0.0001one-sided exact
Primary
Systolic Blood Pressure
Change in systolic blood pressure (SBP) at 9 months as compared to baseline SBP.
Time frame: Baseline and 9 months
Population: Subset of enrolled subjects with available blood pressure data at baseline and 9 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iCAST™ RX Stent System | Systolic Blood Pressure | 15.7 mmHg | Standard Deviation 21.2 |
Comparison: The primary endpoint of systolic blood pressure was analyzed according to the Performance Goal of a decrease in systolic blood pressure of 10 mmHg between procedure and 9 months.p-value: 0.0192t-test, 1 sided
Secondary
Acute Procedural Success
Acute procedural success is defined as technical success without the occurrence of MAE prior to hospital discharge.
Time frame: Day of Procedure, prior to hospital discharge
Population: All enrolled subjects, defined as patients that underwent primary stenting of the target lesion(s) by placement of the iCAST™ RX Stent System. Note that analysis is per subject lesion with available angiography.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| iCAST™ RX Stent System | Acute Procedural Success | 81 Subject-lesions |
Secondary
Change in Number of Anti-Hypertensive Medications
Change in number of anti-hypertensive medications as compared to baseline.
Time frame: Baseline and 9 months
Population: Subset of enrolled subjects with available medication information.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iCAST™ RX Stent System | Change in Number of Anti-Hypertensive Medications | -0.1 Number of Anti-hypertensive Medications | Standard Deviation 0.76 |
Secondary
Change in Renal Function
Renal function compared to baseline as measured by estimated Glomerular Filtration Rate (eGFR) at 9 months.
Time frame: Baseline and 9 months
Population: Subset of enrolled subjects with available eGFR measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iCAST™ RX Stent System | Change in Renal Function | -1.9964 eGFR mL/min/1.73 m^2 | Standard Deviation 13.42781 |
Secondary
Change in Renal Function
Renal function compared to baseline as measured by estimated Glomerular Filtration Rate (eGFR) at 30 days.
Time frame: Baseline and 30 days
Population: Subset of enrolled subjects with available eGFR measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iCAST™ RX Stent System | Change in Renal Function | -0.5520 eGFR mL/min/1.73 m^2 | Standard Deviation 8.42795 |
Secondary
Procedure-Related Major Adverse Events (MAE)
The occurence of procedure-related MAEs is reported as a percentage of subjects with MAE. Inclusive of: 1. Procedure- or device-related occurrence of death 2. Q-Wave myocardial infarction (MI) 3. Clinically driven target lesion revascularization (TLR) 4. Significant embolic events defined as unanticipated kidney/bowel infarct, clinically driven by symptoms of abdominal or back pain and confirmed with CT scan or open surgery; lower extremity ulceration or gangrene; or kidney failure.
Time frame: 30 days, 9 months
Population: All enrolled subjects, defined as patients that underwent primary stenting of the target lesion(s) by placement of the iCAST™ RX Stent System.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| iCAST™ RX Stent System | Procedure-Related Major Adverse Events (MAE) | Overall subjects experiencing MAE | 5 Participants |
| iCAST™ RX Stent System | Procedure-Related Major Adverse Events (MAE) | MAE within 30 days | 0 Participants |
| iCAST™ RX Stent System | Procedure-Related Major Adverse Events (MAE) | MAE within 9 months | 2 Participants |
Secondary
Rate of Incidental TLR
The rate of incidental TLR is the rate of TLRs not meeting the definition of a clinically-driven TLR.
Time frame: 9 months
Population: All enrolled subjects, defined as patients that underwent primary stenting of the target lesion(s) by placement of the iCAST™ RX Stent System. Note that analysis is per subject lesion.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| iCAST™ RX Stent System | Rate of Incidental TLR | 2 Subject-lesions |
Secondary
SBP Control
The change in SBP from baseline to 9 months
Time frame: Baseline and 9 months
Population: Subset of enrolled subjects with available blood pressure measurements at both time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iCAST™ RX Stent System | SBP Control | -15.7 mmHg | Standard Deviation 21.2 |
Secondary
Secondary Patency Rate
Secondary patency rate at 9 months after a clinically-driven TLR which restores patency after total occlusion.
Time frame: 9 months
Population: All enrolled subjects, defined as patients that underwent primary stenting of the target lesion(s) by placement of the iCAST™ RX Stent System. Note that analysis is per subject lesion.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| iCAST™ RX Stent System | Secondary Patency Rate | 3 Subject-lesions |
Secondary
Systolic Blood Pressure (SBP) Control
The change in SBP from baseline to 30 days
Time frame: Baseline and 30 days
Population: Subset of enrolled subjects with available blood pressure measurements at both time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iCAST™ RX Stent System | Systolic Blood Pressure (SBP) Control | -13.6 mmHg | Standard Deviation 18.83 |
Secondary
Target Lesion Revascularization (TLR)
Target Lesion Revascularization (TLR) is measured as the proportion of subjects-lesions that require a clinically-driven reintervention of the target lesion through 9 months. a. A clinically-driven TLR is defined as a TLR (percutaneous balloon angioplasty (PTA), bare metal stent or repeat covered stent deployment, or surgical bypass) due to documented recurrent hypertension from 30-days post-procedure level and/or deterioration in renal function from baseline value, associated with angiographic core laboratory adjudication of a ≥ 60% diameter covered stent restenosis.
Time frame: 9 months
Population: All enrolled subjects, defined as patients that underwent primary stenting of the target lesion(s) by placement of the iCAST™ RX Stent System. Note that analysis is per subject lesion.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| iCAST™ RX Stent System | Target Lesion Revascularization (TLR) | 3 Subject-lesions |
Secondary
Technical Success
Technical success is defined as successful delivery and deployment of the iCAST™ RX Stent System with ≤ 30% residual angiographic stenosis after covered stent deployment (including post-dilatation) assessed via quantitative vascular analysis (QVA) by an independent core laboratory.
Time frame: Day of Procedure
Population: All enrolled subjects, defined as patients that underwent primary stenting of the target lesion(s) by placement of the iCAST™ RX Stent System. Note that analysis is per subject lesion with available angiography.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| iCAST™ RX Stent System | Technical Success | 81 Subject-lesions |