|
|
| General |
| Study Status |
Study Pending |
Application Number /
Requirement Number |
P220023 / PAS002 |
| Date Original Protocol Accepted |
02/05/2024
|
| Date Current Protocol Accepted |
|
| Study Name |
(US GPS) New Enrollment Registry Study
|
| Device Name |
Paradise® Ultrasound Renal Denervation System
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
Objective Performance Criterion
|
| Analysis Type |
Analytical
|
| Study Population |
Transit. Adolescent A (distinctively) : 18-21 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
The Global GPS Registry is designed to evaluate real- world use of the Paradise System in up to 3000 patients at up to 300 clinical centers worldwide. The US GPS Study is the independently powered arm of the GPS Registry. The US GPS study is a multi-center, single-arm post market study and US GPS is designed with similarities in safety reporting and data collection to the overall Global GPS study, which facilitates potential pooling of safety and efficacy data. The US GPS study will include two cohorts: 3. Approximately 30 subjects currently enrolled in the RADIANCE Continued Access Protocol (CAP). 4. Prospective patients treated as per the approved labeling; There is no randomization for prospectively treated patients. The objective of the Global GPS Registry, including the US arm of the Global Paradise System Post Approval Study (US GPS) is to evaluate the real-world use of the Paradise System as per approved labeling. In addition, US GPS will collect data in patient populations underrepresented within the RADIANCE clinical program.
|
| Study Population |
Hypertension patients in whom lifestyle modifications and antihypertensive medications do not adequately control BP identified from the general population by the enrolling center. Patients must meet all inclusion criteria and none of the contraindications for use of the Paradise System, per the Instructions for Use (IFU). Subjects enrolled in the RADIANCE CAP study will be transferred to the US GPS study after completion of their 12-month follow-up visit in the RADIANCE CAP study, to complete the remainder of the long-term annual follow-up visits under the post approval study protocol. Inclusion criteria Patients who meet all of the following inclusion criteria and non of the exclusion criteria should be given consideration • Signed and dated study informed consent • Documented history of hypertension • Documented history of current or prior antihypertensive medication(s) • Mean seated office systolic BP at screening greater than or equal to 140 mmHg • Mean pre-procedure home systolic BP of greater than or equal to 135 mmHg • Estimated glomerular filtration rate (eGFR) of greater than or equal to 30 mL/min/m2 RADIANCE CAP patients must provide signed and dated informed consent for inclusion in long-term follow-up. No other criteria are required for inclusion. Exclusion Criteria Exclusion from the US GPS study will follow the contraindications documented in the approved IFU. The following contraindications listed in the IFU may be determined at the time of procedure prior to treatment: • Renal arteries with diameter < 3mm and > 8mm • Renal artery with fibromuscular dysplasia (FMD) • Stented renal artery • Renal artery aneurysm • Renal artery diameter stenosis >30% • Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter Additional exclusion criteria are: • Patient lacks appropriate renal anatomy for any treatment with the Paradise Catheter • Patient under the age of 18 years old at the time of consent • Patient is pregnant • Patients with transplanted kidney • Presence of abnormal kidney (or secreting adrenal) tumors
|
| Sample Size |
Number of subjects:
The US GPS will enroll a total of 1000 subjects.
Study Sites
Up to 100 clinical sites in the USA will be enrolled. A minimum of 20% and a maximum of 40% of the total sites will have prior ultrasound RDN experience.
The total number of treated patients at a single center will be limited to a maximum of 20% of the total study sample size to prevent any single center from unduly influencing study outcomes.
The US GPS will enroll patients within the following subgroups, at least
.
• 250 evaluable female
• 150 evaluable Black/African Americans
• 100 evaluable Hispanic
• 50 evaluable Asian (or other)
In addition, enrollment of at least 50 subjects will also be targeted
• Elderly (persons = 65yrs old)
• Heart failure (NYHA Class II-IV with any ejection fraction)
Number of subjects:
The US GPS will enroll a total of 1000 subjects.
Study Sites
Up to 100 clinical sites in the USA will be enrolled. A minimum of 20% and a maximum of 40% of the total sites will have prior ultrasound RDN experience.
The total number of treated patients at a single center will be limited to a maximum of 20% of the total study sample size to prevent any single center from unduly influencing study outcomes.
The US GPS will enroll patients within the following subgroups, at least
.
• 250 evaluable female
• 150 evaluable Black/African Americans
• 100 evaluable Hispanic
• 50 evaluable Asian (or other)
In addition, enrollment of at least 50 subjects will also be targeted
• Elderly (persons = 65yrs old)
• Heart failure (NYHA Class II-IV with any ejection fraction)
• Type 2 Diabetes
• Stage 3 chronic kidney disease (eGFR<60; but >30)
• Atrial arrhythmias (documented history of AT/AF)
• Orthostatic hypertension at screening (increase in office BP when standing as compared with sitting of =20 mmHg systolic and/or =10 mmHg diastolic)
Effectiveness Assumptions
Effectiveness: BP reduction. A total sample size of 1000 patients, with up to approximately 15% attrition for an evaluable sample size of 850 patients, will provide adequate power for a range of plausible effect sizes of interest for the BP reduction endpoint.
With a -5 mmHg lower confidence bound, the minimum mean difference required would be -6.9 mmHg assuming an enrolled sample size of 1,000 patients and a standard deviation of 20.
Effectiveness: Subject Responder
For the responder co-primary endpoint, assuming a true responder rate of 57%, an evaluable sample size will also provide approximately 82% power.
The assumed responder rate of 55% is based on the expectation that response in a real-world patient population may be lower than the response rate observed in the controlled clinical study population.
Safety Assumptions
The proposed sample size of 1000 enrolled patients would allow 95% probability of detecting clinical events with an occurrence rate as low as 0.3%.
|
| Key Study Endpoints |
Primary Effectiveness Endpoints
Two co-primary endpoints will be evaluated for primary effectiveness.
Co-Primary Endpoint #1: Group mean home Systolic BP
reduction at 3 months
Co-Primary Endpoint #2: Subject Responder at 3 months
A subject will be defined as a responder if they achieve any of the following:
• Control in home BP (defined as systolic BP <130 mmHg) at 3 months and/or
• Absolute reduction in home systolic BP fall = 5 mmHg at 3 months and/or
• Reduction in medication burden measured using defined daily dose (DDD)*
*Where a meaningful outcome will be considered a change in the cumulative medication burden (DDD) of at least 0.3
Durability of Effectiveness
To evaluate the durability of effectiveness of the Paradise system, both endpoints above will be evaluated at 12 months post procedure.
Secondary Effectiveness Assessments from [baseline to 1, 3, 6, 12, 24, 36, 48 & 60 months] include
• Change in mean home systolic/diastolic blood pressure in mmHg
• Change in mean office systolic/diastolic blood pressure in mmHg
• Change in home and office heart rate
• Change in home and office pules pressure
• Change in the number and/ or dosage and/or type of antihypertensive medications taken
• Change in patient reported outcomes
Other Secondary Effectiveness Assessments
• Percentage of patients who are controlled as measured by various cut points of home BP (control to be assessed as both < 130 mmHg systolic and <135 mmHg systolic) office BP (control to also be assessed as <130 mmHg and <140 mmHg systolic)
• Percentage of patients who demonstrate a reduction in home systolic BP of = 5mmHg, = 10 mmHg and = 15 mmHg at 3, 6, 12, 24, 36, 48 and 60 months compared to baseline
• Percentage of patients who demonstrate a reduction in office systolic BP of = 5mmHg, = 10 mmHg and = 15 mmHg at 3, 6, 12, 24, 36, 48 and 60 months compared to baseline
• Change in home and office heart rate at 1, 3, 6, 12, 24, 36, 48 and 60 months compared to baseline
Safety Endpoints (Secondary Endpoints)
Data to be presented as an incidence rate from > 30 days post procedure and annually:
• Death from any cause
• Hospitalization for
o Major cardiovascular or hemodynamic events
o Hypertensive crisis or symptomatic hypotension
• New onset stroke; TIA, CVA or other major cerebrovascular event
• Acute myocardial infarction
• Coronary revascularization
• Major vascular complications
• Kidney-related adverse events
• Adverse drug reaction due to antihypertensive medication
|
| Follow-up Visits and Length of Follow-up |
Prospectively enrolled patients will be followed at 1, 3, 6, 12, 24-, 36-, 48- and 60-months post procedure. Screening, treatment, 1-, 3- & 12-month follow-up visits will be done in office. Six (6), 24-, 36-, 48- and 60-month visits may be conducted remotely.
|
|
