SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study

Hypertension Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02439749
• Other study ID #: SPYRAL HTN-OFF MED
• Status: Completed
• Phase: N/A
• Start date: June 2015
• Est. completion date: October 25, 2023

Study information

• Verified date: April 2024
• Source: Medtronic Vascular
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 366
• Est. completion date: October 25, 2023
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Hypertension
• Vascular Diseases

Intervention

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.

Locations

Country	Name	City	State
Australia	Alfred Hospital	Melbourne	Victoria
Austria	Klinikum Wels-Grieskirchen	Wels
Canada	Institut de cardiologie de Montréal / Montreal Heart Institute	Montréal	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Germany	Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH	Bad Krozingen
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum des Saarlandes	Homburg
Germany	Herzzentrum Leipzig, Universitätsklinik	Leipzig
Germany	Sana Kliniken Lübeck	Lübeck
Greece	Hippokration General Hospital of Athens	Athens
Greece	University General Hospital of Thessaloniki (AHEPA)	Thessaloniki
Ireland	Galway University Hospital	Galway
Japan	Mitsui Memorial Hospital	Chiyoda	Tokyo
Japan	Jichi Medical University Hospital	Shimotsuke	Tochigi
United Kingdom	Cardiff and Vale University Health Board - University Hospital of Wales	Cardiff
United Kingdom	Royal Devon & Exeter NHS Foundation Trust	Exeter
United Kingdom	Imperial College Healthcare NHS Trust	London
United States	AnMed Health	Anderson	South Carolina
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Piedmont Heart Institute	Atlanta	Georgia
United States	Charleston Area Medical Center	Charleston	West Virginia
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Baylor Heart & Vascular Hospital	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	PinnacleHealth Cardiovascular Institute	Harrisburg	Pennsylvania
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Heart Center Research, LLC	Huntsville	Alabama
United States	Baptist Medical Center Jacksonville	Jacksonville	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Kaiser Permanente LA Medical Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	Centennial Medical Center	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Mount Sinai Medical Center	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	St Joseph Mercy Oakland	Pontiac	Michigan
United States	The Miriam Hospital	Providence	Rhode Island
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Honor Health Research Institute	Scottsdale	Arizona
United States	Providence Hospital	Southfield	Michigan
United States	Stanford Hospital and Clinics	Stanford	California
United States	Tallahassee Research Institute	Tallahassee	Florida
United States	Cardiology Associates Research LLC	Tupelo	Mississippi
United States	Iowa Heart Center	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Vascular

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Germany,  Greece,  Ireland,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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, however endpoint data is reported to 3 months only)	From baseline to 1 month post-procedure
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.	From baseline to 3 months post-procedure
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.	From baseline to 3 months post-procedure
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)	From baseline to 1 month post-procedure
Secondary	Number of Participants With Renal Artery Perforation Requiring Intervention	Renal artery perforation requiring intervention	From baseline to 1 month post-procedure
Secondary	Renal Artery Dissection	Number of Participants with Renal artery dissection requiring intervention	From baseline to 1 month post-procedure
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).	From baseline to 1 month post-procedure
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	From baseline to 1 month post-procedure
Secondary	Number of Participants With Decline in eGFR	=40% decline in eGFR	From baseline to 1 month post-procedure
Secondary	Myocardial Infarction	Number of Participants with New myocardial infarction	From baseline to 1 month post-procedure
Secondary	New Stroke	Number of Participants with New stroke	From baseline to 1 month post-procedure
Secondary	Number of Participants With Renal Artery Re-intervention	Renal artery re-intervention	From baseline to 1 month post-procedure
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).	From baseline to 1 month post-procedure
Secondary	Number of Participants With Increase in Serum Creatinine	Increase in serum creatinine > 50% from screening visit 2.	From baseline to 1 month post-procedure
Secondary	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
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.	From baseline to 1 month post-procedure
Secondary	Number of Participants With All-cause Mortality	All-cause mortality	From baseline to 3 months post-procedure
Secondary	Number of Participants With Change in Systolic Blood Pressure as Measured by 24-hour ABPM		From baseline to 36 month post-procedure
Secondary	Number of Participants With Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140 mmHg)		From 1 month to 36 months post-procedure
Secondary	Number of Participants With Change in Office Diastolic Blood Pressure	Change in office diastolic blood pressure	From baseline to 36 months post-procedure
Secondary	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
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	From baseline to 3 months post randomization
Secondary	Number of Participants With =40% Decline in eGFR	=40% Decline in eGFR	From baseline to 3 months post randomization
Secondary	Number of Participants With New Myocardial Infarction	New Myocardial Infarction	From baseline to 3 months post randomization
Secondary	New Stroke	Number of Participants with New Stroke	From baseline to 3 months post randomization
Secondary	Number of Participants With Renal Artery Re-intervention	Renal Artery Re-intervention	From baseline to 3 months post randomization
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).	From baseline to 3 months post randomization
Secondary	Increase in Serum Creatinine	Number of Participants with Increase in Serum Creatinine > 50% from screening visit 2.	From baseline to 3 months post randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in Office Diastolic Blood Pressure	Change in office diastolic blood pressure from baseline (Screening Visit 2)	From baseline to 1 month post procedure
Secondary	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
Secondary	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