SPYRAL PIVOTAL – SPYRAL HTN-OFF MED Study

Overview

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.

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Participant)
  • Study Primary Completion Date: April 30, 2020

Interventions

  • Device: 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.
  • Procedure: 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.

Arms, Groups and Cohorts

  • Experimental: Renal Denervation
    • Renal angiography and Renal Denervation (Symplicity Spyral™ multi-electrode renal denervation system)
  • Sham Comparator: Sham Procedure
    • Renal angiography

Clinical Trial Outcome Measures

Primary Measures

  • Number of Participants With Major Adverse Events (MAE) Defined as a Composite of Events.
    • Time Frame: From baseline to 1 month post-procedure
    • 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)
  • Baseline Adjusted Change (Using Analysis of Covariance) in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring
    • Time Frame: 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.

Secondary Measures

  • Baseline Adjusted Change (Using Analysis of Covariance) in Office Systolic Blood Pressure
    • Time Frame: 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 Significant Embolic Event Resulting in End-organ Damage
    • Time Frame: 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 Renal Artery Perforation Requiring Intervention
    • Time Frame: From baseline to 1 month post-procedure
    • Renal artery perforation requiring intervention
  • Renal Artery Dissection
    • Time Frame: From baseline to 1 month post-procedure
    • Number of Participants with Renal artery dissection requiring intervention
  • Number of Participants With Vascular Complications
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: From baseline to 1 month post-procedure
    • ≥40% decline in eGFR
  • Myocardial Infarction
    • Time Frame: From baseline to 1 month post-procedure
    • Number of Participants with New myocardial infarction
  • New Stroke
    • Time Frame: From baseline to 1 month post-procedure
    • Number of Participants with New stroke
  • Number of Participants With Renal Artery Re-intervention
    • Time Frame: From baseline to 1 month post-procedure
    • Renal artery re-intervention
  • Number of Participants With Major Bleeding According to TIMI Definition
    • Time Frame: 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
    • Time Frame: From baseline to 1 month post-procedure
    • Increase in serum creatinine > 50% from screening visit 2.
  • Number of Participants With New Renal Artery Stenosis > 70%
    • Time Frame: From baseline to 6 month post-procedure
    • Confirmed by angiography and as determined by the angiographic core laboratory.
  • Number of Participants With Hospitalization for Hypertensive Crisis With Medications or the Protocol
    • Time Frame: From baseline to 1 month post-procedure
    • Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications or the protocol.
  • Number of Participants With All-cause Mortality
    • Time Frame: From baseline to 3 months post-procedure
    • All-cause mortality
  • Number of Participants With Change in Systolic Blood Pressure as Measured by 24-hour ABPM
    • Time Frame: From baseline to 36 month post-procedure
  • Number of Participants With Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140 mmHg)
    • Time Frame: From 1 month to 36 months post-procedure
  • Number of Participants With Change in Office Diastolic Blood Pressure
    • Time Frame: From baseline to 36 months post-procedure
    • Change in office diastolic blood pressure
  • Number of Participants With Change in Diastolic Blood Pressure as Measured by 24-hour ABPM
    • Time Frame: From baseline to 36 months post-procedure
    • Change in diastolic blood pressure as measured by 24-hour ABPM
  • Number of Participants With End-Stage Renal Disease (ESRD)
    • Time Frame: 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 ≥40% Decline in eGFR
    • Time Frame: From baseline to 3 months post randomization
    • ≥40% Decline in eGFR
  • Number of Participants With New Myocardial Infarction
    • Time Frame: From baseline to 3 months post randomization
    • New Myocardial Infarction
  • New Stroke
    • Time Frame: From baseline to 3 months post randomization
    • Number of Participants with New Stroke
  • Number of Participants With Renal Artery Re-intervention
    • Time Frame: From baseline to 3 months post randomization
    • Renal Artery Re-intervention
  • Number of Participants With Major Bleeding According to TIMI Definition
    • Time Frame: From baseline to 3 months post randomization
    • 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).
  • Increase in Serum Creatinine
    • Time Frame: 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
    • Time Frame: From baseline to 3 months post randomization
    • Hospitalization for Hypertensive Crisis Not Related to Confirmed Nonadherence With Medications or the Protocol
  • Change in Office Systolic Blood Pressure
    • Time Frame: From baseline to 1 month post procedure
    • Change in office systolic blood pressure from baseline (Screening Visit 2) to 1-month
  • Number of Participants Achieving Target Office Systolic Blood Pressure
    • Time Frame: From baseline to 1 month post procedure
    • Incidence of achieving target office systolic blood pressure (SBP <140 mmHg)
  • Number of Participants Achieving Target Office Systolic Blood Pressure
    • Time Frame: From baseline to 3 months post procedure
    • Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140 mmHg)
  • Change in Office Diastolic Blood Pressure
    • Time Frame: From baseline to 1 month post procedure
    • Change in office diastolic blood pressure from baseline (Screening Visit 2)
  • Change in Office Diastolic Blood Pressure
    • Time Frame: From baseline to 3 months post procedure
    • Change in Office Diastolic Blood Pressure From Baseline (Screening Visit 2) to 3-months
  • Change in Diastolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM)
    • Time Frame: 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).

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 20 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Medtronic Vascular
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Raymond Townsend, MD, Principal Investigator, University of Pennsylvania
    • David Kandzari, MD, Principal Investigator, Piedmont Hospital
    • Michael Böhm, MD, Principal Investigator, Universitätskliniken des Saarlandes
    • Kazuomi Kario, MD, Principal Investigator, Jichi Medical University

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