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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02439749




Registration number
NCT02439749
Ethics application status
Date submitted
28/04/2015
Date registered
12/05/2015
Date last updated
22/06/2021

Titles & IDs
Public title
SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study
Scientific 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)
Secondary ID [1] 0 0
SPYRAL HTN-OFF MED
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 0 0
Vascular Diseases 0 0
Cardiovascular Diseases 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Symplicity Spyral™ multi-electrode renal denervation system
Treatment: Surgery - Sham Procedure

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

Sham Comparator: Sham Procedure - Renal angiography


Treatment: Devices: 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.

Treatment: Surgery: 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.

Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
From baseline to 1 month post-procedure
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
From baseline to 3 months post-procedure
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
From baseline to 3 months post-procedure
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
From baseline to 1 month post-procedure
Secondary outcome [3] 0 0
Number of Participants With Renal Artery Perforation Requiring Intervention - Renal artery perforation requiring intervention
Timepoint [3] 0 0
From baseline to 1 month post-procedure
Secondary outcome [4] 0 0
Renal Artery Dissection - Number of Participants with Renal artery dissection requiring intervention
Timepoint [4] 0 0
From baseline to 1 month post-procedure
Secondary outcome [5] 0 0
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).
Timepoint [5] 0 0
From baseline to 1 month post-procedure
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
From baseline to 1 month post-procedure
Secondary outcome [7] 0 0
Number of Participants With Decline in eGFR - =40% decline in eGFR
Timepoint [7] 0 0
From baseline to 1 month post-procedure
Secondary outcome [8] 0 0
Myocardial Infarction - Number of Participants with New myocardial infarction
Timepoint [8] 0 0
From baseline to 1 month post-procedure
Secondary outcome [9] 0 0
New Stroke - Number of Participants with New stroke
Timepoint [9] 0 0
From baseline to 1 month post-procedure
Secondary outcome [10] 0 0
Number of Participants With Renal Artery Re-intervention - Renal artery re-intervention
Timepoint [10] 0 0
From baseline to 1 month post-procedure
Secondary outcome [11] 0 0
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).
Timepoint [11] 0 0
From baseline to 1 month post-procedure
Secondary outcome [12] 0 0
Number of Participants With Increase in Serum Creatinine - Increase in serum creatinine > 50% from screening visit 2.
Timepoint [12] 0 0
From baseline to 1 month post-procedure
Secondary outcome [13] 0 0
Number of Participants With New Renal Artery Stenosis > 70% - Confirmed by angiography and as determined by the angiographic core laboratory.
Timepoint [13] 0 0
From baseline to 6 month post-procedure
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
From baseline to 1 month post-procedure
Secondary outcome [15] 0 0
Number of Participants With All-cause Mortality - All-cause mortality
Timepoint [15] 0 0
From baseline to 3 months post-procedure
Secondary outcome [16] 0 0
Number of Participants With Change in Systolic Blood Pressure as Measured by 24-hour ABPM
Timepoint [16] 0 0
From baseline to 36 month post-procedure
Secondary outcome [17] 0 0
Number of Participants With Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140 mmHg)
Timepoint [17] 0 0
From 1 month to 36 months post-procedure
Secondary outcome [18] 0 0
Number of Participants With Change in Office Diastolic Blood Pressure - Change in office diastolic blood pressure
Timepoint [18] 0 0
From baseline to 36 months post-procedure
Secondary outcome [19] 0 0
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
Timepoint [19] 0 0
From baseline to 36 months post-procedure
Secondary outcome [20] 0 0
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
Timepoint [20] 0 0
From baseline to 3 months post randomization
Secondary outcome [21] 0 0
Number of Participants With =40% Decline in eGFR - =40% Decline in eGFR
Timepoint [21] 0 0
From baseline to 3 months post randomization
Secondary outcome [22] 0 0
Number of Participants With New Myocardial Infarction - New Myocardial Infarction
Timepoint [22] 0 0
From baseline to 3 months post randomization
Secondary outcome [23] 0 0
New Stroke - Number of Participants with New Stroke
Timepoint [23] 0 0
From baseline to 3 months post randomization
Secondary outcome [24] 0 0
Number of Participants With Renal Artery Re-intervention - Renal Artery Re-intervention
Timepoint [24] 0 0
From baseline to 3 months post randomization
Secondary outcome [25] 0 0
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).
Timepoint [25] 0 0
From baseline to 3 months post randomization
Secondary outcome [26] 0 0
Increase in Serum Creatinine - Number of Participants with Increase in Serum Creatinine > 50% from screening visit 2.
Timepoint [26] 0 0
From baseline to 3 months post randomization
Secondary outcome [27] 0 0
Number of Participants With Hospitalization for Hypertensive Crisis - Hospitalization for Hypertensive Crisis Not Related to Confirmed Nonadherence With Medications or the Protocol
Timepoint [27] 0 0
From baseline to 3 months post randomization
Secondary outcome [28] 0 0
Change in Office Systolic Blood Pressure - Change in office systolic blood pressure from baseline (Screening Visit 2) to 1-month
Timepoint [28] 0 0
From baseline to 1 month post procedure
Secondary outcome [29] 0 0
Number of Participants Achieving Target Office Systolic Blood Pressure - Incidence of achieving target office systolic blood pressure (SBP <140 mmHg)
Timepoint [29] 0 0
From baseline to 1 month post procedure
Secondary outcome [30] 0 0
Number of Participants Achieving Target Office Systolic Blood Pressure - Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140 mmHg)
Timepoint [30] 0 0
From baseline to 3 months post procedure
Secondary outcome [31] 0 0
Change in Office Diastolic Blood Pressure - Change in office diastolic blood pressure from baseline (Screening Visit 2)
Timepoint [31] 0 0
From baseline to 1 month post procedure
Secondary outcome [32] 0 0
Change in Office Diastolic Blood Pressure - Change in Office Diastolic Blood Pressure From Baseline (Screening Visit 2) to 3-months
Timepoint [32] 0 0
From baseline to 3 months post procedure
Secondary outcome [33] 0 0
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).
Timepoint [33] 0 0
From baseline to 3 months post procedure

Eligibility
Key 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.
Minimum age
20 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Mississippi
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Rhode Island
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
West Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Wisconsin
Country [24] 0 0
Austria
State/province [24] 0 0
Wels
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
Germany
State/province [27] 0 0
Bad Krozingen
Country [28] 0 0
Germany
State/province [28] 0 0
Erlangen
Country [29] 0 0
Germany
State/province [29] 0 0
Homburg
Country [30] 0 0
Germany
State/province [30] 0 0
Leipzig
Country [31] 0 0
Germany
State/province [31] 0 0
Lübeck
Country [32] 0 0
Greece
State/province [32] 0 0
Athens
Country [33] 0 0
Greece
State/province [33] 0 0
Thessaloniki
Country [34] 0 0
Ireland
State/province [34] 0 0
Galway
Country [35] 0 0
Japan
State/province [35] 0 0
Tochigi
Country [36] 0 0
Japan
State/province [36] 0 0
Tokyo
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Cardiff
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Exeter
Country [39] 0 0
United Kingdom
State/province [39] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Medtronic Vascular
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02439749
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Raymond Townsend, MD
Address 0 0
University of Pennsylvania
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications