SPYRAL HTN-ON MED Study

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that renal denervation decreases blood pressure and is safe when studied in the presence of up to three standard antihypertensive medications.

Official Title
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Global Clinical Study of Renal Denervation With the Symplicity Spyral™ Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension on Standard Medical Therapy (SPYRAL HTN-ON MED)

Conditions
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Hypertension, Vascular Diseases, Cardiovascular Diseases

Intervention / Treatment
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* Device: Symplicity Spyral™ multi-electrode renal denervation system
* Procedure: Sham Procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individual has office systolic blood pressure (SBP) ≥ 150 mmHg and <180 mmHg and a diastolic blood pressure (DBP) ≥ 90 mmHg when receiving a medication regimen of one, two, or three antihypertensive medication classes. Individual has 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average SBP ≥ 140 mmHg and < 170 mmHg. Exclusion Criteria: Individual lacks appropriate renal artery anatomy. Individual has estimated glomerular filtration rate (eGFR) of <45. Individual has type 1 diabetes mellitus or poorly-controlled type 2 diabetes mellitus. Individual has one or more episodes of orthostatic hypotension. Individual requires chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea. Individual has primary pulmonary hypertension. Individual is pregnant, nursing or planning to become pregnant. Individual has frequent intermittent or chronic pain that results in treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for two or more days per week over the month prior to enrollment Individual has stable or unstable angina within 3 months of enrollment, myocardial infarction within 3 months of enrollment; heart failure, cerebrovascular accident or transient ischemic attack, or atrial fibrillation at any time. Individual works night shifts.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Renal Denervation<br>Renal angiography and Renal Denervation (Symplicity Spyral™ multi-electrode renal denervation system) | Device: Symplicity Spyral™ multi-electrode renal denervation system<br>* After a renal angiography according to standard procedures, subjects remain blinded and are immediately treated with the renal denervation procedure after randomization.<br>* Other names: Renal Denervation;|
| Sham Comparator: Sham Procedure<br>Renal angiography | Procedure: Sham Procedure<br>* After a renal angiography according to standard procedures, subjects remain blinded and remain on the catheterization lab table for at least 20 minutes prior to introducer sheath removal.<br>* Other names: Renal angiography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and Chronic Safety by Evaluating Incidence of Major Adverse Events | The primary safety endpoint of the study is the incidence of Major Adverse Events (MAE), defined as a composite of the following events: All-cause mortality, End Stage Renal Disease (ESRD), Significant embolic event resulting in end-organ damage, Renal artery perforation requiring intervention, Renal artery dissection requiring intervention, Vascular complications, Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications or the protocol, New renal artery stenosis >70%, confirmed by angiography and as a determined by the angiographic core laboratory, through one-month post-randomization (6- months for new renal artery stenosis). | From baseline to 1 month post-procedure (6 months for new renal artery stenosis) | 
| Change in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM) | Baseline adjusted change (using Analysis of Covariance) in systolic blood pressure (SBP) from baseline (Screening Visit 2) to 6 months post-procedure as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM). | From baseline to 6 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Office Systolic Blood Pressure | Change in office systolic blood pressure from baseline (Screening Visit 2) to 6 months post-procedure | From baseline to 6 months post-procedure | 
| Antihypertensive Medication Usage and Changes to 6-months | Number of medications from baseline (Screening Visit 2) through 6 Months post-procedure | From baseline to 6-month post-procedure | 
| Antihypertensive Medication Burden to 6-months | Based on the prescribed medications reported, medication burden was calculated using Medication Index 2 score which is a composite index based on the doses of antihypertensive medications multiplied by the number of medications prescribed; all classes (ACE/ARB, calcium channel blockers, etc.) were considered equivalent in potency. Higher score indicates higher dosages being prescribed over the standard dose. Minimum value 0; No Maximum value | From baseline to 6 Months post-procedure | 
| Medication Changes | Patients who had medication changes based on Medication Index 2 drug testing data. Medication Index 2 score is a composite index based on the doses of antihypertensive medications multiplied by the number of medications prescribed; all classes (ACE/ARB, calcium channel blockers, etc.) were considered equivalent in potency. | Baseline to 6-months post-procedure | 
| Incidence of Achieving Target Office Systolic Blood Pressure | Incidence of achieving target office systolic blood pressure (SBP<140 mmHg) at 6 months post- procedure. | From baseline to 6 months post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uncontrolled hypertension, Renal denervation