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SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study

Not Applicable
Completed
Conditions
Hypertension
Vascular Diseases
Cardiovascular Diseases
Interventions
Device: Symplicity Spyral™ multi-electrode renal denervation system
Procedure: Sham Procedure
Registration Number
NCT02439749
Lead Sponsor
Medtronic Vascular
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
366
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Renal DenervationSymplicity Spyral™ multi-electrode renal denervation systemRenal angiography and Renal Denervation (Symplicity Spyral™ multi-electrode renal denervation system)
Sham ProcedureSham ProcedureRenal angiography
Primary Outcome Measures
NameTimeMethod
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)

Baseline Adjusted Change (Using Analysis of Covariance) in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure MonitoringFrom 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 Outcome Measures
NameTimeMethod
New StrokeFrom baseline to 3 months post randomization

Number of Participants with New Stroke

Number of Participants With Renal Artery Re-interventionFrom baseline to 36 months post randomization

Renal Artery Re-intervention

Number of Participants With Major Bleeding According to TIMI DefinitionFrom baseline to 36 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).

Number of Participants With Increase in Serum CreatinineFrom 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 ProtocolFrom 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 PressureFrom baseline to 36 months post procedure

Change in Office Systiloc Blood Pressure From Baseline (Screening Visit 2) to 36 months.

Change in Office Diastolic Blood PressureFrom baseline to 36 months post-procedure

Change in office diastolic blood pressure

Number of Participants Achieving Target Office Systolic Blood PressureFrom baseline to 3 months post procedure

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

Baseline Adjusted Change (Using Analysis of Covariance) in Office Systolic Blood PressureFrom 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 All-cause MortalityFrom baseline to 36 months post-randomization
Number of Participants With ≥40% Decline in eGFRFrom baseline to 36 months post randomization

≥40% Decline in eGFR

Number of Participants With End-Stage Renal Disease (ESRD)From baseline to 36 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 InfarctionFrom baseline to 36 months post randomization

New Myocardial Infarction

Increase in Serum CreatinineFrom 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 CrisisFrom baseline to 36 months post randomization

Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications orthe protocol

Change in Diastolic Blood Pressure as Measured by 24-hour ABPMFrom baseline to 36 months post-procedure

Change in diastolic blood pressure as measured by 24-hour ABPM

Number of Participants With New Renal Artery Stenosis > 70%From baseline to 36 months post randomization

Confirmed by angiography and as determined by the angiographic core laboratory.

Change in Systolic Blood Pressure as Measured by 24-hour ABPMFrom 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 StrokeFrom baseline to 36 months post randomization

New Stroke

Number of Participants With an Increase in Serum CreatinineFrom baseline to 36 months post randomization

Number of Participants with Increase in Serum Creatinine \> 50% from screening visit 2.

Number of Participants With Significant Embolic Event Resulting in End-organ DamageFrom 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 InterventionFrom baseline to 1 month post-procedure

Renal artery perforation requiring intervention

Renal Artery DissectionFrom baseline to 1 month post-procedure

Number of Participants with Renal artery dissection requiring intervention

Number of Participants With Vascular ComplicationsFrom 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 DiseaseFrom 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 eGFRFrom baseline to 1 month post-procedure

≥40% decline in eGFR

Myocardial InfarctionFrom baseline to 1 month post-procedure

Number of Participants with New myocardial infarction

Trial Locations

Locations (47)

Saint Barnabas Medical Center

🇺🇸

Livingston, New Jersey, United States

Tallahassee Research Institute

🇺🇸

Tallahassee, Florida, United States

Klinikum Wels-Grieskirchen

🇦🇹

Wels, Austria

Universitätsklinikum des Saarlandes

🇩🇪

Homburg, Germany

Emory University Hospital Midtown

🇺🇸

Atlanta, Georgia, United States

Piedmont Heart Institute

🇺🇸

Atlanta, Georgia, United States

North Shore University Hospital

🇺🇸

Manhasset, New York, United States

Mitsui Memorial Hospital

🇯🇵

Chiyoda, Tokyo, Japan

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

University Hospitals Cleveland Medical Center

🇺🇸

Cleveland, Ohio, United States

Galway University Hospital

🇮🇪

Galway, Ireland

The Miriam Hospital

🇺🇸

Providence, Rhode Island, United States

Royal Devon & Exeter NHS Foundation Trust

🇬🇧

Exeter, United Kingdom

Heart Center Research, LLC

🇺🇸

Huntsville, Alabama, United States

Honor Health Research Institute

🇺🇸

Scottsdale, Arizona, United States

Stanford Hospital and Clinics

🇺🇸

Stanford, California, United States

Kaiser Permanente LA Medical Center

🇺🇸

Los Angeles, California, United States

Baptist Medical Center Jacksonville

🇺🇸

Jacksonville, Florida, United States

Iowa Heart Center

🇺🇸

West Des Moines, Iowa, United States

St Joseph Mercy Oakland

🇺🇸

Pontiac, Michigan, United States

Hattiesburg Clinic

🇺🇸

Hattiesburg, Mississippi, United States

Providence Hospital

🇺🇸

Southfield, Michigan, United States

Cardiology Associates Research LLC

🇺🇸

Tupelo, Mississippi, United States

Barnes-Jewish Hospital

🇺🇸

Saint Louis, Missouri, United States

Mount Sinai Medical Center

🇺🇸

New York, New York, United States

Hospital of the University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

PinnacleHealth Cardiovascular Institute

🇺🇸

Harrisburg, Pennsylvania, United States

AnMed Health

🇺🇸

Anderson, South Carolina, United States

Baylor Heart & Vascular Hospital

🇺🇸

Dallas, Texas, United States

Charleston Area Medical Center

🇺🇸

Charleston, West Virginia, United States

Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

St. Michael's Hospital

🇨🇦

Toronto, Ontario, Canada

Institut de cardiologie de Montréal / Montreal Heart Institute

🇨🇦

Montréal, Quebec, Canada

Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH

🇩🇪

Bad Krozingen, Germany

Universitätsklinikum Erlangen

🇩🇪

Erlangen, Germany

Hippokration General Hospital of Athens

🇬🇷

Athens, Greece

Sana Kliniken Lübeck

🇩🇪

Lübeck, Germany

Herzzentrum Leipzig, Universitätsklinik

🇩🇪

Leipzig, Germany

University General Hospital of Thessaloniki (AHEPA)

🇬🇷

Thessaloniki, Greece

Imperial College Healthcare NHS Trust

🇬🇧

London, United Kingdom

Cardiff and Vale University Health Board - University Hospital of Wales

🇬🇧

Cardiff, United Kingdom

Jichi Medical University Hospital

🇯🇵

Shimotsuke, Tochigi, Japan

Yale New Haven Hospital

🇺🇸

New Haven, Connecticut, United States

Minneapolis Heart Institute Foundation

🇺🇸

Minneapolis, Minnesota, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Centennial Medical Center

🇺🇸

Nashville, Tennessee, United States

Aurora St. Luke's Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

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