SPYRAL HTN-ON MED Study of Renal Denervation With the Symplicity Spyral™ Multi-electrode Renal Denervation System

Medtronic Vascular337 enrolled

Overview

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.

The purpose of this study is to test the hypothesis that renal denervation is safe and reduces systolic blood pressure (SBP) in patients with uncontrolled hypertension on one, two, or three standard antihypertensive medications compared to a sham control in the same population. In this study, "uncontrolled hypertension" is defined as an office systolic blood pressure (SBP) ≥ 150 mmHg and \<180 mmHg, an office Diastolic Blood Pressure (DBP) ≥90 mmHg and a 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average SBP ≥140 mmHg to \<170 mmHg, all of which are measured at Screening Visits. Data obtained will be used to confirm the effect of renal denervation on elevated blood pressure in patients on 1, 2 or 3 antihypertensive medications.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

337

Conditions

Hypertension Vascular Diseases Cardiovascular Diseases

Interventions

Symplicity Spyral™ multi-electrode renal denervation systemDEVICE

After a renal angiography according to standard procedures, subjects remain blinded and are immediately treated with the renal denervation procedure after randomization.

Sham ProcedurePROCEDURE

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.

Eligibility

Sex: ALLMin age: 20 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (56)

Outcomes

Primary Outcomes

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).

Time frame: From baseline to 6 months post-procedure

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 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 determined by the angiographic core laboratory, through one-month post-randomization (6-months for new renal artery stenosis)

Time frame: From Baseline to 1 month post-procedure (6 months for new renal artery stenosis)

Secondary Outcomes

Change in Office Systolic Blood Pressure to 6-months

Change in office systolic blood pressure from baseline (Screening Visit 2) to 6 months post-procedure

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Heart Center Research, LLC

Huntsville, Alabama, United States

Stanford Hospital and Clinics

Stanford, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Washington DC VA Medical Center

Washington D.C., District of Columbia, United States

Baptist Medical Center Jacksonville

Jacksonville, Florida, United States

Memorial Hospital Jacksonville

Jacksonville, Florida, United States

Tallahassee Research Institute

Tallahassee, Florida, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Piedmont Heart Institute

Atlanta, Georgia, United States

Iowa Heart Center

West Des Moines, Iowa, United States

...and 46 more locations

Time frame: 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.

Time frame: 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.

Time frame: From baseline to 6 months post-procedure

Change in Systolic Blood Pressure as Measured by 24-hour ABPM 12 Months

Change in systolic blood pressure from baseline (screening visit 2) to 12 months as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM)

Time frame: From Baseline to 12 months post procedure

Change in Systolic Blood Pressure as Measured by 24-hour ABPM 24-months

Change in systolic blood pressure from baseline (screening visit 2) to 24 months as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM).

Time frame: From baseline to 24 months post-procedure

Change in Systolic Blood Pressure as Measured by 24-hour ABPM 36-months

Change in systolic blood pressure from baseline (screening visit 2) to 36 months as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM).

Time frame: From baseline to 36 months post-procedure

Change in Office Systolic Blood Pressure to 12-months

Change in office systolic blood pressure from baseline (screening visit 2) to 12 months.

Time frame: From Baseline to 12 months post procedure

Change in Office Systolic Blood Pressure to 24-months

Change in office systolic blood pressure from baseline (screening visit 2) to 24 months.

Time frame: From baseline to 24 months post-procedure

Change in Office Systolic Blood Pressure to 36-months

Change in office systolic blood pressure from baseline (screening visit 2) to 36 months.

Time frame: From baseline to 36 months post-procedure

Change in Diastolic Blood Pressure as Measured by 24-hour ABPM 12-months

Change in diastolic blood pressure from baseline (screening visit 2) to 12 months as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM).

Time frame: From Baseline to 12 months post procedure

Change in Diastolic Blood Pressure as Measured by 24-hour ABPM 24-months

Change in diastolic blood pressure from baseline (screening visit 2) to 24 months as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM).

Time frame: From baseline to 24 months post-procedure

Change in Diastolic Blood Pressure as Measured by 24-hour ABPM 36-months

Change in diastolic blood pressure from baseline (screening visit 2) to 36 months as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM).

Time frame: From baseline to 36 months post-procedure

Change in Office Diastolic Blood Pressure 12 Months

Change in office diastolic blood pressure from baseline (screening visit 2) to 12 months.

Time frame: From baseline to 12 months post-procedure

Change in Office Diastolic Blood Pressure 24 Months

Change in office diastolic blood pressure from baseline (screening visit 2) to 24 months.

Time frame: From baseline to 24 months post-procedure

Change in Office Diastolic Blood Pressure 36 Months

Change in office diastolic blood pressure from baseline (screening visit 2) to 36 months.

Time frame: From baseline to 36 months post-procedure

Number of Participants Achieving Target Office Systolic Blood Pressure 12 Months

Incidence of Achieving Target Office Systolic Blood Pressure (SBP \<140 mmHg)

Time frame: From baseline to 12 months post-procedure

Number of Participants Achieving Target Office Systolic Blood Pressure 24 Months

Incidence of Achieving Target Office Systolic Blood Pressure (SBP \<140 mmHg).

Time frame: From baseline to 24 months post-procedure

Number of Participants Achieving Target Office Systolic Blood Pressure. 36 Months

Incidence of Achieving Target Office Systolic Blood Pressure (SBP \<140 mmHg)

Time frame: From baseline to 36 months post-procedure

Number of Participants With All Cause Mortality

Time frame: From Baseline to 36-months post procedure

Number of Participants With End-Stage Renal Disease (ESRD)

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

Time frame: From Baseline to 36-months post-procedure

Number of Participants With Significant Embolic Event Resulting in End-organ Damage

Time frame: From Baseline to 36 months post-procedure

Number of Participants With Renal Artery Perforation Requiring Intervention

Renal artery perforation requiring intervention

Time frame: From Baseline to 36 month post-procedure

Number of Participants With Renal Artery Dissection Requiring Intervention

Number of Participants with Renal artery dissection requiring intervention

Time frame: From Baseline to 36 months 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).

Time frame: From Baseline to 36 months post-procedure

Number of Participants With Hospitalization for Hypertensive Crisis Not Related to Confirmed Non-adherence With Medications and/or the Protocol.

Time frame: From Baseline to 36 months post-procedure

Number of Participants With New Renal Artery Stenosis > 70%, Confirmed by Angiography and as Determined by the Angiographic Core Laboratory

Time frame: From Baseline to 36 months post-procedure

Number of Participants With ≥ 40% Decline in eGFR

Time frame: From baseline to 36 months post-procedure

Number of Participants With Increase in Serum Creatinine >50% From Screening Visit 2 (Baseline)

Time frame: From baseline to 36 months post-procedure

Number of Participants With New Myocardial Infarct

Time frame: From baseline to 36 months post-procedure

Number of Participants With New Stroke

Time frame: From baseline to 36 months post-procedure

Number of Participants With Renal Artery Re-intervention

Time frame: From baseline to 36 months 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

Time frame: From baseline to 36 months post-procedure

Change in Diastolic Blood Pressure as Measured by 24-hour (ABPM) 6-months

Change in diastolic blood pressure from baseline (screening visit 2) to 6 months as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM).

Time frame: From baseline to 6 months post-procedure

Change in Office Diastolic Blood Pressure to 6-months

Change in office diastolic blood pressure from baseline (screening visit 2) to 6 months post-procedure

Time frame: From baseline to 6 months post-procedure