Cardiovascular Diseases, Hypertension, Vascular Diseases
Conditions
Keywords
Uncontrolled hypertension, Renal denervation
Brief summary
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.
Interventions
After a renal angiography according to standard procedures, subjects remain blinded and are immediately treated with the renal denervation procedure after randomization.
PROCEDURESham Procedure
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.
Sponsors
Medtronic Vascular
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Adjusted Change (Using Analysis of Covariance) in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring | From baseline to 3 months post-procedure | 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. |
| Number of Participants With Major Adverse Events (MAE) Defined as a Composite of Events. | From baseline to 1 month post-procedure (6 months for new renal artery stenosis) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Artery Dissection | From baseline to 1 month post-procedure | Number of Participants with Renal artery dissection requiring intervention |
| Number of Participants With Vascular Complications | From baseline to 1 month post-procedure | 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). |
| Number of Participants With End-stage Renal Disease | From baseline to 1 month post-procedure | 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 |
| Number of Participants With Decline in eGFR | From baseline to 1 month post-procedure | ≥40% decline in eGFR |
| Myocardial Infarction | From baseline to 1 month post-procedure | Number of Participants with New myocardial infarction |
| New Stroke | From baseline to 1 month post-procedure | Number of Participants with New stroke |
| Number of Participants With Renal Artery Re-intervention | From baseline to 1 month post-procedure | Renal artery re-intervention |
| Number of Participants With Major Bleeding According to TIMI Definition | From baseline to 1 month post-procedure | 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). |
| Number of Participants With Increase in Serum Creatinine | From baseline to 1 month post-procedure | Increase in serum creatinine \> 50% from screening visit 2. |
| Number of Participants With Hospitalization for Hypertensive Crisis With Medications or the Protocol | From baseline to 1 month post-procedure | Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications or the protocol. |
| Change in Office Systolic Blood Pressure | From baseline to 1 month post procedure | Change in office systolic blood pressure from baseline (Screening Visit 2) to 1-month |
| Change in Office Diastolic Blood Pressure | From baseline to 1 month post procedure | Change in office diastolic blood pressure from baseline (Screening Visit 2) |
| Number of Participants Achieving Target Office Systolic Blood Pressure | From baseline to 1 month post procedure | Incidence of achieving target office systolic blood pressure (SBP \<140 mmHg) |
| Number of Participants With Significant Embolic Event Resulting in End-organ Damage | From baseline to 1 month post-procedure | 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) |
| Number of Participants With All-cause Mortality | From baseline to 3 months post-procedure | All-cause mortality |
| Number of Participants With ≥40% Decline in eGFR | From baseline to 3 months post randomization | ≥40% Decline in eGFR |
| Number of Participants With End-Stage Renal Disease (ESRD) | From baseline to 3 months post randomization | 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 |
| Number of Participants With New Myocardial Infarction | From baseline to 3 months post randomization | New Myocardial Infarction |
| Increase in Serum Creatinine | From baseline to 3 months post randomization | Number of Participants with Increase in Serum Creatinine \> 50% from screening visit 2. |
| Number of Participants With Hospitalization for Hypertensive Crisis | From baseline to 3 months post randomization | Hospitalization for Hypertensive Crisis Not Related to Confirmed Nonadherence With Medications or the Protocol |
| Change in Diastolic Blood Pressure as Measured by 24-hour ABPM | From baseline to 3 months post procedure | Change in diastolic blood pressure from baseline (screening visit 2) to 3-month as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM). |
| Number of Participants With New Renal Artery Stenosis > 70% | From baseline to 6 month post-procedure | Confirmed by angiography and as determined by the angiographic core laboratory. |
| 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 baseline to 36 months post-procedure | — |
| Number of Participants With New Stroke | From baseline to 36 months post randomization | New Stroke |
| Number of Participants With an Increase in Serum Creatinine | From baseline to 36 months post randomization | Number of Participants with Increase in Serum Creatinine \> 50% from screening visit 2. |
| Baseline Adjusted Change (Using Analysis of Covariance) in Office Systolic Blood Pressure | From baseline to 3 months post-procedure | 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. |
| Number of Participants With Renal Artery Perforation Requiring Intervention | From baseline to 1 month post-procedure | Renal artery perforation requiring intervention |
Other
| Measure | Time frame | Description |
|---|---|---|
| Antihypertensive Medication Burden to 36-months | From baseline to 36 months post-procedure | 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. There are no clinically established thresholds. |
Countries
Australia, Austria, Canada, Germany, Greece, Ireland, Japan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Renal Denervation Renal angiography and Renal Denervation (Symplicity Spyral™ multi-electrode renal denervation system)
Symplicity Spyral™ multi-electrode renal denervation system: After a renal angiography according to standard procedures, subjects remain blinded and are immediately treated with the renal denervation procedure after randomization. | 182 |
| Sham Procedure Renal angiography
Sham Procedure: 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. | 184 |
| Total | 366 |
Baseline characteristics
| Characteristic | Sham Procedure | Total | Renal Denervation |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 41 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 167 Participants | 325 Participants | 158 Participants |
| Age, Continuous | 52.7 years STANDARD_DEVIATION 10.1 | 52.6 years STANDARD_DEVIATION 10.45 | 52.5 years STANDARD_DEVIATION 10.8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 9 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 32 Participants | 69 Participants | 37 Participants |
| Race/Ethnicity, Customized Japanese from Japan | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 87 Participants | 165 Participants | 78 Participants |
| Race/Ethnicity, Customized White | 60 Participants | 116 Participants | 56 Participants |
| Region of Enrollment Australia | 6 participants | 13 participants | 7 participants |
| Region of Enrollment Austria | 4 participants | 7 participants | 3 participants |
| Region of Enrollment Canada | 2 participants | 5 participants | 3 participants |
| Region of Enrollment Germany | 38 participants | 72 participants | 34 participants |
| Region of Enrollment Greece | 30 participants | 58 participants | 28 participants |
| Region of Enrollment Ireland | 7 participants | 14 participants | 7 participants |
| Region of Enrollment Japan | 2 participants | 5 participants | 3 participants |
| Region of Enrollment United Kingdom | 10 participants | 16 participants | 6 participants |
| Region of Enrollment United States | 85 participants | 176 participants | 91 participants |
| Sex: Female, Male Female | 56 Participants | 121 Participants | 65 Participants |
| Sex: Female, Male Male | 128 Participants | 245 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 182 | 2 / 184 |
| other Total, other adverse events | 149 / 182 | 155 / 184 |
| serious Total, serious adverse events | 38 / 182 | 36 / 184 |
Outcome results
Primary
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.
Time frame: From baseline to 3 months post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Baseline Adjusted Change (Using Analysis of Covariance) in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring | -4.5 mmHg | Standard Deviation 10.8 |
| Sham Procedure | Baseline Adjusted Change (Using Analysis of Covariance) in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring | -0.6 mmHg | Standard Deviation 8.7 |
Primary
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)
Time frame: From baseline to 1 month post-procedure (6 months for new renal artery stenosis)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Major Adverse Events (MAE) Defined as a Composite of Events. | 0 Participants |
| Sham Procedure | Number of Participants With Major Adverse Events (MAE) Defined as a Composite of Events. | 0 Participants |
Secondary
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.
Time frame: From baseline to 3 months post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Baseline Adjusted Change (Using Analysis of Covariance) in Office Systolic Blood Pressure | -9.4 mmHg | Standard Deviation 14.8 |
| Sham Procedure | Baseline Adjusted Change (Using Analysis of Covariance) in Office Systolic Blood Pressure | -2.3 mmHg | Standard Deviation 12.7 |
Secondary
Change in Diastolic Blood Pressure as Measured by 24-hour ABPM
Change in diastolic blood pressure as measured by 24-hour ABPM
Time frame: From baseline to 36 months post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Change in Diastolic Blood Pressure as Measured by 24-hour ABPM | -11.7 mmHg | Standard Deviation 9.6 |
| Sham Procedure | Change in Diastolic Blood Pressure as Measured by 24-hour ABPM | -15.0 mmHg | Standard Deviation 8 |
p-value: 0.052ANCOVA
Secondary
Change in Diastolic Blood Pressure as Measured by 24-hour ABPM
Change in diastolic blood pressure from baseline (screening visit 2) to 3-month as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM).
Time frame: From baseline to 3 months post procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Change in Diastolic Blood Pressure as Measured by 24-hour ABPM | -3.5 mmHg | Standard Deviation 6.7 |
| Sham Procedure | Change in Diastolic Blood Pressure as Measured by 24-hour ABPM | -0.8 mmHg | Standard Deviation 5.7 |
p-value: <0.001ANCOVA
Secondary
Change in Office Diastolic Blood Pressure
Change in office diastolic blood pressure
Time frame: From baseline to 36 months post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Change in Office Diastolic Blood Pressure | -10.8 mmHg | Standard Deviation 10.4 |
| Sham Procedure | Change in Office Diastolic Blood Pressure | -15.4 mmHg | Standard Deviation 10.8 |
p-value: 0.009ANCOVA
Secondary
Change in Office Diastolic Blood Pressure
Change in office diastolic blood pressure from baseline (Screening Visit 2)
Time frame: From baseline to 1 month post procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Change in Office Diastolic Blood Pressure | -5.3 mmHg | Standard Deviation 8.3 |
| Sham Procedure | Change in Office Diastolic Blood Pressure | -2.9 mmHg | Standard Deviation 7.6 |
Secondary
Change in Office Diastolic Blood Pressure
Change in Office Diastolic Blood Pressure From Baseline (Screening Visit 2) to 3-months
Time frame: From baseline to 3 months post procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Change in Office Diastolic Blood Pressure | -5.0 mmHg | Standard Deviation 8.3 |
| Sham Procedure | Change in Office Diastolic Blood Pressure | -1.0 mmHg | Standard Deviation 8 |
Secondary
Change in Office Systolic Blood Pressure
Change in Office Systiloc Blood Pressure From Baseline (Screening Visit 2) to 36 months.
Time frame: From baseline to 36 months post procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Change in Office Systolic Blood Pressure | -21.9 mmHg | Standard Deviation 15.5 |
| Sham Procedure | Change in Office Systolic Blood Pressure | -26.4 mmHg | Standard Deviation 12.8 |
p-value: 0.07ANCOVA
Secondary
Change in Office Systolic Blood Pressure
Change in office systolic blood pressure from baseline (Screening Visit 2) to 1-month
Time frame: From baseline to 1 month post procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Change in Office Systolic Blood Pressure | -10.2 mmHg | Standard Deviation 14 |
| Sham Procedure | Change in Office Systolic Blood Pressure | -5.7 mmHg | Standard Deviation 11.8 |
Secondary
Change in Systolic Blood Pressure as Measured by 24-hour ABPM
Time frame: From baseline to 36 month post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Change in Systolic Blood Pressure as Measured by 24-hour ABPM | -16.2 mmHg | Standard Deviation 14.6 |
| Sham Procedure | Change in Systolic Blood Pressure as Measured by 24-hour ABPM | -22.0 mmHg | Standard Deviation 13.3 |
p-value: 0.026ANCOVA
Secondary
Increase in Serum Creatinine
Number of Participants with Increase in Serum Creatinine \> 50% from screening visit 2.
Time frame: From baseline to 3 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Increase in Serum Creatinine | 0 Participants |
| Sham Procedure | Increase in Serum Creatinine | 0 Participants |
Secondary
Myocardial Infarction
Number of Participants with New myocardial infarction
Time frame: From baseline to 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Myocardial Infarction | 0 Participants |
| Sham Procedure | Myocardial Infarction | 0 Participants |
Secondary
New Stroke
Number of Participants with New stroke
Time frame: From baseline to 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | New Stroke | 0 Participants |
| Sham Procedure | New Stroke | 0 Participants |
Secondary
New Stroke
Number of Participants with New Stroke
Time frame: From baseline to 3 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | New Stroke | 0 Participants |
| Sham Procedure | New Stroke | 1 Participants |
Secondary
Number of Participants Achieving Target Office Systolic Blood Pressure
Incidence of Achieving Target Office Systolic Blood Pressure (SBP \<140 mmHg)
Time frame: From baseline to 3 months post procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants Achieving Target Office Systolic Blood Pressure | 27 Participants |
| Sham Procedure | Number of Participants Achieving Target Office Systolic Blood Pressure | 12 Participants |
Secondary
Number of Participants Achieving Target Office Systolic Blood Pressure
Incidence of achieving target office systolic blood pressure (SBP \<140 mmHg)
Time frame: From baseline to 1 month post procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants Achieving Target Office Systolic Blood Pressure | 32 Participants |
| Sham Procedure | Number of Participants Achieving Target Office Systolic Blood Pressure | 11 Participants |
Secondary
Number of Participants With ≥40% Decline in eGFR
≥40% Decline in eGFR
Time frame: From baseline to 36 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With ≥40% Decline in eGFR | 1 Participants |
| Sham Procedure | Number of Participants With ≥40% Decline in eGFR | 0 Participants |
Secondary
Number of Participants With ≥40% Decline in eGFR
≥40% Decline in eGFR
Time frame: From baseline to 3 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With ≥40% Decline in eGFR | 0 Participants |
| Sham Procedure | Number of Participants With ≥40% Decline in eGFR | 0 Participants |
Secondary
Number of Participants With All-cause Mortality
All-cause mortality
Time frame: From baseline to 3 months post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With All-cause Mortality | 0 Participants |
| Sham Procedure | Number of Participants With All-cause Mortality | 0 Participants |
Secondary
Number of Participants With All-cause Mortality
Time frame: From baseline to 36 months post-randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With All-cause Mortality | 0 Participants |
| Sham Procedure | Number of Participants With All-cause Mortality | 1 Participants |
Secondary
Number of Participants With an Increase in Serum Creatinine
Number of Participants with Increase in Serum Creatinine \> 50% from screening visit 2.
Time frame: From baseline to 36 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With an Increase in Serum Creatinine | 1 Participants |
| Sham Procedure | Number of Participants With an Increase in Serum Creatinine | 0 Participants |
Secondary
Number of Participants With Decline in eGFR
≥40% decline in eGFR
Time frame: From baseline to 1 month post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Decline in eGFR | 0 Participants |
| Sham Procedure | Number of Participants With Decline in eGFR | 0 Participants |
Secondary
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
Time frame: From baseline to 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With End-stage Renal Disease | 0 Participants |
| Sham Procedure | Number of Participants With End-stage Renal Disease | 0 Participants |
Secondary
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
Time frame: From baseline to 3 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With End-Stage Renal Disease (ESRD) | 0 Participants |
| Sham Procedure | Number of Participants With End-Stage Renal Disease (ESRD) | 0 Participants |
Secondary
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
Time frame: From baseline to 36 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment are at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With End-Stage Renal Disease (ESRD) | 0 Participants |
| Sham Procedure | Number of Participants With End-Stage Renal Disease (ESRD) | 0 Participants |
Secondary
Number of Participants With Hospitalization for Hypertensive Crisis
Hospitalization for Hypertensive Crisis Not Related to Confirmed Nonadherence With Medications or the Protocol
Time frame: From baseline to 3 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Hospitalization for Hypertensive Crisis | 1 Participants |
| Sham Procedure | Number of Participants With Hospitalization for Hypertensive Crisis | 0 Participants |
Secondary
Number of Participants With Hospitalization for Hypertensive Crisis
Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications orthe protocol
Time frame: From baseline to 36 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Hospitalization for Hypertensive Crisis | 1 Participants |
| Sham Procedure | Number of Participants With Hospitalization for Hypertensive Crisis | 2 Participants |
Secondary
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.
Time frame: From baseline to 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Hospitalization for Hypertensive Crisis With Medications or the Protocol | 0 Participants |
| Sham Procedure | Number of Participants With Hospitalization for Hypertensive Crisis With Medications or the Protocol | 0 Participants |
Secondary
Number of Participants With Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140) mmHg)
Time frame: From baseline to 36 months post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140) mmHg) | 70 Participants |
| Sham Procedure | Number of Participants With Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140) mmHg) | 33 Participants |
Secondary
Number of Participants With Increase in Serum Creatinine
Increase in serum creatinine \> 50% from screening visit 2.
Time frame: From baseline to 1 month post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Increase in Serum Creatinine | 1 Participants |
| Sham Procedure | Number of Participants With Increase in Serum Creatinine | 0 Participants |
Secondary
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 randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Major Bleeding According to TIMI Definition | 0 Participants |
| Sham Procedure | Number of Participants With Major Bleeding According to TIMI Definition | 2 Participants |
Secondary
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 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Major Bleeding According to TIMI Definition | 0 Participants |
| Sham Procedure | Number of Participants With Major Bleeding According to TIMI Definition | 0 Participants |
Secondary
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 3 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Major Bleeding According to TIMI Definition | 0 Participants |
| Sham Procedure | Number of Participants With Major Bleeding According to TIMI Definition | 0 Participants |
Secondary
Number of Participants With New Myocardial Infarction
New Myocardial Infarction
Time frame: From baseline to 36 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With New Myocardial Infarction | 0 Participants |
| Sham Procedure | Number of Participants With New Myocardial Infarction | 0 Participants |
Secondary
Number of Participants With New Myocardial Infarction
New Myocardial Infarction
Time frame: From baseline to 3 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With New Myocardial Infarction | 0 Participants |
| Sham Procedure | Number of Participants With New Myocardial Infarction | 0 Participants |
Secondary
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 randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With New Renal Artery Stenosis > 70% | 0 Participants |
| Sham Procedure | Number of Participants With New Renal Artery Stenosis > 70% | 0 Participants |
Secondary
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 6 month post-procedure
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With New Renal Artery Stenosis > 70% | 0 Participants |
| Sham Procedure | Number of Participants With New Renal Artery Stenosis > 70% | 0 Participants |
Secondary
Number of Participants With New Stroke
New Stroke
Time frame: From baseline to 36 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With New Stroke | 0 Participants |
| Sham Procedure | Number of Participants With New Stroke | 3 Participants |
Secondary
Number of Participants With Renal Artery Perforation Requiring Intervention
Renal artery perforation requiring intervention
Time frame: From baseline to 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Renal Artery Perforation Requiring Intervention | 0 Participants |
| Sham Procedure | Number of Participants With Renal Artery Perforation Requiring Intervention | 0 Participants |
Secondary
Number of Participants With Renal Artery Re-intervention
Renal Artery Re-intervention
Time frame: From baseline to 36 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Renal Artery Re-intervention | 0 Participants |
| Sham Procedure | Number of Participants With Renal Artery Re-intervention | 0 Participants |
Secondary
Number of Participants With Renal Artery Re-intervention
Renal artery re-intervention
Time frame: From baseline to 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Renal Artery Re-intervention | 0 Participants |
| Sham Procedure | Number of Participants With Renal Artery Re-intervention | 0 Participants |
Secondary
Number of Participants With Renal Artery Re-intervention
Renal Artery Re-intervention
Time frame: From baseline to 3 months post randomization
Population: The number of participants analyzed reflects the number of subjects within each treatment arm who have data available for outcome measure analysis. This number can be variable from the number of subjects in each treatment arm at study start.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Renal Artery Re-intervention | 0 Participants |
| Sham Procedure | Number of Participants With Renal Artery Re-intervention | 0 Participants |
Secondary
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)
Time frame: From baseline to 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Significant Embolic Event Resulting in End-organ Damage | 0 Participants |
| Sham Procedure | Number of Participants With Significant Embolic Event Resulting in End-organ Damage | 0 Participants |
Secondary
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 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Number of Participants With Vascular Complications | 0 Participants |
| Sham Procedure | Number of Participants With Vascular Complications | 1 Participants |
Secondary
Renal Artery Dissection
Number of Participants with Renal artery dissection requiring intervention
Time frame: From baseline to 1 month post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Denervation | Renal Artery Dissection | 0 Participants |
| Sham Procedure | Renal Artery Dissection | 0 Participants |
Other Pre-specified
Antihypertensive Medication Burden to 36-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. There are no clinically established thresholds.
Time frame: From baseline to 36 months post-procedure
Population: The number of participants analyzed reflects the number of subjects with prescribed medications reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Denervation | Antihypertensive Medication Burden to 36-months | 2.09 Medication Index 2 Score | Standard Deviation 2.4 |
| Sham Procedure | Antihypertensive Medication Burden to 36-months | 3.20 Medication Index 2 Score | Standard Deviation 3.6 |