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| General |
| Study Status |
Study Pending |
Application Number /
Requirement Number |
P220026 / PAS002 |
| Date Original Protocol Accepted |
02/15/2024
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| Date Current Protocol Accepted |
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| Study Name |
SPYRAL AFFIRM PAS: New Enrollment Registry Study
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| Device Name |
Symplicity Spyral™ Renal Denervation System
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Analytical
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| Study Population |
Transit. Adolescent A (distinctively) : 18-21 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
The SPYRAL AFFIRM study is a multi-center, international, prospective, interventional, single arm study designed to investigate renal denervation in a real-world population with a focus on the safety, efficacy, and durability of the procedure in subjects with varying severity of hypertension and associated comorbidities. The SPYRAL AFFIRM study will evaluate the long-term safety, efficacy, and durability of the Symplicity Spyral system in the full population and several subgroups. The data will be used to complement data from the SPYRAL PIVOTAL-SPYRAL HTN-OFF MED trial, SPYRAL HTN-ON MED trial, as well as the Global SYMPLICITY Registry
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| Study Population |
The study population will consist of two cohorts:
a) Main Cohort: The SPYRAL AFFIRM Main Cohort will consist of all subjects consented to the AFFIRM study who undergo the renal denervation procedure once enrolled.
• ABPM Subset: The SPYRAL AFFIRM study will also collect ABPM data for the first 250 Main Cohort subjects who have a initial valid ABPM at baseline.
b) Continuation Cohort: SPYRAL AFFIRM sites that also participate in the SPYRAL PIVOTAL-SPYRAL HTN-OFF MED and/or SPYRAL HTN-ON MED studies can enroll subjects initially randomized to the treatment arm and successfully treated via the renal denervation procedure for continued follow up through 60 months after the renal denervation procedure they received in the aforementioned studies. All subjects that meet the criteria above are eligible to be consented for continued follow up in the SPYRAL AFFIRM study within one week (+ or -) of exit from the prior study.
All subjects in the Main Cohort, must meet all Inclusion and no Exclusion criteria prior to undergoing the RDN procedure.
For subjects in the Continuation Cohort, all Inclusion/Exclusion criteria will need to have been met at the time of their initial procedure in the SPYRAL PIVOTAL- SPYRAL-HTN OFF MED or SPYRAL HTN-ON MED study participation.
Intent-to-Treat (ITT): all subjects who signed and dated informed consent form, met the enrollment criteria and the renal denervation therapy is delivered (i.e., the catheter is delivered through the guide catheter with the intention to provide the renal denervation treatment). This will be the primary analysis set for this study.
Per-Protocol (PP): The ITT population excluding subjects who do not meet certain key entry criteria. The analysis of the primary endpoint will be repeated for PP set as a secondary analysis.
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| Sample Size |
Number of subjects:
Approximately 1300 subjects will be treated in the study, with a minimum of 700 subjects from the US.
A minimum number of subjects (US & Non-US) will be enrolled in the following key subgroups: 300 females, 200 Black Americans (US only), 150 age >65, 50 subjects with Type 2 diabetes, 75 subjects with eGFR<60 ml/min/1.73m2 and 100 subjects of Hispanic
ethnicity.
Continuation Cohort: Up to 100 eligible RDN treated subjects who participated in the SPYRAL PIVOTAL-SPYRAL HTN-OFF MED and
SPYRAL HTN-ON MED clinical trials, at sites that are participating in the AFFIRM study, will continue to be followed through 60 months post RDN procedure.
Assumptions for sample size estimation:
The change in office SBP at 6 months is expected to be -8.7 mmHg (US IDE studies) with a standard deviation of 20 mmHg. The performance goal is set at -6.0 mmHg, which represents 69% of the expected reduction of the primary endpoint in this subgroup (US cohort) and is chosen to represent a clinically meaningful blood pressure reduction.
A one-sided Alpha = 0.025 level of significance, an evaluable sample size of 550 treated subjects yields 88% power to reject the null hypothesis in favor of the alternative.
Approximately 1300 subjects will be treated in the study of
which a minimum of 700 will be from the US.
The total study sample size will be up to 1400 (including 100 Continuation cohort). PASS 2021 one sample t-test was used for the sample size calculation.
Number of sites: Main Cohort: The study is expected to be conducted at approximately 100 study sites.
Sites location: Greater than 50% of sites will be in the United Sates with additional sites in OUS.
To ensure distribution of subjects across sites and geographies, an investigative site may enroll up to 10% of the total study sample.
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| Key Study Endpoints |
Effectiveness Endpoints
Primary: Office Systolic Blood Pressure (SBP) change at 6 months
The primary endpoint will be compared to the prespecified performance goal at 6 months for the subjects treated in the US.
Efficacy objectives will be evaluated for all Main Cohort subjects and for US subjects in the Main Cohort at each follow up visit based on subject cohort assignment.
Secondary Endpoints:
• Change in OBP from baseline at 3, 12, 24, 36, 48 and 60-months post-procedure
• Change in home blood pressure (HBP) from baseline at 3, 6, 12, 24, 36 months post-procedure (Main Cohort only)
• Change in 24-hour blood pressure from baseline including day and night independently (ABPM Subset & Continuation Cohort) at 3, 6, 12, 24, 36, 48 and 60-months post-procedure
• Change in OBP, HBP and 24-hour blood pressure from baseline will be assessed in each of the subgroups as applicable:
• Percent of subjects achieving blood pressure target reduction and control of =140 mmHg as measured by OBP, HBP and ABPM
• Time subject’s blood pressure is controlled through 36-month follow-up or study exit
• Characterization of anti-hypertensive medication burden over time
• Change from baseline in quality of life as measured by the EQ-5D instrument, and change in patients’ HTN health status measures
• Evaluation of laboratory and clinical characteristics for predictors of response to renal denervation
• Percent of subjects requiring repeat renal denervation
• Evaluation of blood pressure as measured by OBP, HBP and ABPM, adjusting for anti-hypertensive medication burden through 36- months
Safety Endpoints (Secondary Endpoints)
Secondary:
(for all Main Cohort subjects and the Continuation Cohort
• Incidence of major adverse events (MAE) at 3, 6, 12, 24, 36, 48 and 60-months post procedure:
• Composite safety objective (All-cause mortality, End-stage renal disease, Significant embolic event, Renal artery perforation requiring intervention etc.)
• greater than or equal to 40% decline in eGFR from baseline
• Incidence of increase in serum creatinine >50% from baseline
• Incidence of myocardial infarction
• Incidence of stroke
• Renal artery re-intervention
• Major bleeding according to TIMI definition (i.e. intracranial hemorrhage, greater than or equal to5g/dl decrease in hemoglobin concentration, a greater than or equal to 15% absolute decrease in hematocrit, or death due to bleeding within 7 days of the procedure)
• Slope of eGFR
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| Follow-up Visits and Length of Follow-up |
3 years post procedure
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