SPYRAL PIVOTAL - SPYRAL HTN-OFF 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 absence of 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 in the Absence of Antihypertensive Medications (SPYRAL PIVOTAL - SPYRAL HTN-OFF 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 after being off medications. Individual has 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average SBP ≥ 140 mmHg and < 170 mmHg. Individual is willing to discontinue current antihypertensive medications. 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 |
| --- | --- | --- |
| Number of Participants With Major Adverse Events (MAE) Defined as a Composite of 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% (6 months for new renal artery stenosis, however endpoint data is reported to 3 months only) | From baseline to 1 month post-procedure | 
| Baseline Adjusted Change (Using Analysis of Covariance) in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring | The outcome measure is the change in ambulatory systolic blood pressure from baseline to 3-month. The unadjusted treatment difference between renal denervation and sham control groups is -3.9 mmHg. The baseline adjusted treatment difference is -3.9 mmHg. | From baseline to 3 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Adjusted Change (Using Analysis of Covariance) in Office Systolic Blood Pressure | The outcome measure is the change in office systolic blood pressure from baseline to 3-month. The unadjusted treatment difference between renal denervation and sham control groups is -7.0 mmHg. The baseline adjusted treatment difference is -6.9 mmHg. | From baseline to 3 months post-procedure | 
| Number of Participants With Significant Embolic Event Resulting in End-organ Damage | Significant embolic event resulting in end-organ damage (e.g. kidney/bowel infarct, lower extremity ulceration or gangrene, or doubling of serum creatinine documented by at least two measurements at least 21 days apart) | From baseline to 1 month post-procedure | 
| Number of Participants With Renal Artery Perforation Requiring Intervention | Renal artery perforation requiring intervention | From baseline to 1 month post-procedure | 
| Renal Artery Dissection | Number of Participants with Renal artery dissection requiring intervention | From baseline to 1 month post-procedure | 
| Number of Participants With Vascular Complications | Vascular complications (e.g., clinically significant groin hematoma, arteriovenous fistula, pseudoaneurysm, excessive bleeding) requiring surgical repair, interventional procedure, thrombin injection, or blood transfusion (requiring more than 2 units of packed red blood cells within any 24 hour period during the first 7 days post renal denervation procedure). | From baseline to 1 month post-procedure | 
| Number of Participants With End-stage Renal Disease | defined as two or more eGFR measurements < 15 mL/min/1.73m2 at least 21 days apart and requiring dialysis for one of more of the following: Volume management refractory to diuretics Hyperkalemia unmanageable by diet and diuretics Acidosis bicarbonate <18 unmanageable with HCO3 supplements Symptoms of uremia, nausea, vomiting | From baseline to 1 month post-procedure | 
| Number of Participants With Decline in eGFR | ≥40% decline in eGFR | From baseline to 1 month post-procedure | 
| Myocardial Infarction | Number of Participants with New myocardial infarction | From baseline to 1 month post-procedure | 
| New Stroke | Number of Participants with New stroke | From baseline to 1 month post-procedure | 
| Number of Participants With Renal Artery Re-intervention | Renal artery re-intervention | From baseline to 1 month post-procedure | 
| Number of Participants With Major Bleeding According to TIMI Definition | Major bleeding according to TIMI definition (i.e. intracranial hemorrhage, ≥5g/dl decrease in hemoglobin concentration, a ≥15% absolute decrease in hematocrit, or death due to bleeding within 7 days of the procedure). | From baseline to 1 month post-procedure | 
| Number of Participants With Increase in Serum Creatinine | Increase in serum creatinine > 50% from screening visit 2. | From baseline to 1 month post-procedure | 
| Number of Participants With New Renal Artery Stenosis > 70% | Confirmed by angiography and as determined by the angiographic core laboratory. | From baseline to 6 month post-procedure | 
| Number of Participants With Hospitalization for Hypertensive Crisis With Medications or the Protocol | Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications or the protocol. | From baseline to 1 month post-procedure | 
| Number of Participants With All-cause Mortality | All-cause mortality | From baseline to 3 months post-procedure | 
| Number of Participants With Change in Systolic Blood Pressure as Measured by 24-hour ABPM |  | From baseline to 36 month post-procedure | 
| Number of Participants With Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140 mmHg) |  | From 1 month to 36 months post-procedure | 
| Number of Participants With Change in Office Diastolic Blood Pressure | Change in office diastolic blood pressure | From baseline to 36 months post-procedure | 
| Number of Participants With Change in Diastolic Blood Pressure as Measured by 24-hour ABPM | Change in diastolic blood pressure as measured by 24-hour ABPM | From baseline to 36 months post-procedure | 
| Number of Participants With End-Stage Renal Disease (ESRD) | Defined as two or more eGFR measurements < 15 mL/min/1.73m2 at least 21 days apart and requiring dialysis for one of more of the following: Volume management refractory to diuretics Hyperkalemia unmanageable by diet and diuretics Acidosis bicarbonate <18 unmanageable with HCO3 supplements Symptoms of uremia, nausea, vomiting | From baseline to 3 months post randomization | 
| Number of Participants With ≥40% Decline in eGFR | ≥40% Decline in eGFR | From baseline to 3 months post randomization | 
| Number of Participants With New Myocardial Infarction | New Myocardial Infarction | From baseline to 3 months post randomization | 
| New Stroke | Number of Participants with New Stroke | From baseline to 3 months post randomization | 
| Number of Participants With Renal Artery Re-intervention | Renal Artery Re-intervention | From baseline to 3 months post randomization | 
| Number of Participants With Major Bleeding According to TIMI Definition | Major bleeding according to TIMI definition (i.e. intracranial hemorrhage, ≥5g/dl decrease in hemoglobin concentration, a ≥15% absolute decrease in hematocrit, or death due to bleeding within 7 days of the procedure). | From baseline to 3 months post randomization | 
| Increase in Serum Creatinine | Number of Participants with Increase in Serum Creatinine > 50% from screening visit 2. | From baseline to 3 months post randomization | 
| Number of Participants With Hospitalization for Hypertensive Crisis | Hospitalization for Hypertensive Crisis Not Related to Confirmed Nonadherence With Medications or the Protocol | From baseline to 3 months post randomization | 
| Change in Office Systolic Blood Pressure | Change in office systolic blood pressure from baseline (Screening Visit 2) to 1-month | From baseline to 1 month post procedure | 
| Number of Participants Achieving Target Office Systolic Blood Pressure | Incidence of achieving target office systolic blood pressure (SBP <140 mmHg) | From baseline to 1 month post procedure | 
| Number of Participants Achieving Target Office Systolic Blood Pressure | Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140 mmHg) | From baseline to 3 months post procedure | 
| Change in Office Diastolic Blood Pressure | Change in office diastolic blood pressure from baseline (Screening Visit 2) | From baseline to 1 month post procedure | 
| Change in Office Diastolic Blood Pressure | Change in Office Diastolic Blood Pressure From Baseline (Screening Visit 2) to 3-months | From baseline to 3 months post procedure | 
| Change in Diastolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM) | Change in diastolic blood pressure from baseline (screening visit 2) to 3-month as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM). | From baseline to 3 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