Back to resultsSPYRAL HTN-ON MED Study
Primary Purpose
Hypertension, Vascular Diseases, Cardiovascular Diseases
Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Symplicity Spyral™ multi-electrode renal denervation system
Sham Procedure
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension focused on measuring Uncontrolled hypertension, Renal denervation
Eligibility Criteria
Inclusion Criteria:
- Individual has office systolic blood pressure (SBP) ≥ 150 mmHg and <180 mmHg and a diastolic blood pressure (DBP) ≥ 90 mmHg when receiving a medication regimen of one, two, or three antihypertensive medication classes.
- Individual has 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average SBP ≥ 140 mmHg and < 170 mmHg.
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.
Sites / Locations
- Heart Center Research, LLC
- Stanford Hospital and Clinics
- Washington DC VA Medical Center
- Baptist Medical Center Jacksonville
- Memorial Hospital Jacksonville
- Tallahassee Research Institute
- Emory University Hospital Midtown
- Piedmont Heart Institute
- Iowa Heart Center
- University of Kentucky
- St Joseph Mercy Oakland
- Providence Hospital
- Minneapolis Heart Institute Foundation
- Hattiesburg Clinic
- Cardiology Associates Research LLC
- Barnes-Jewish Hospital
- Saint Barnabas Medical Center
- North Shore University Hospital
- Weill Cornell Medical College/The New York Presbyterian Hospital
- Mount Sinai Medical Center
- Duke University Medical Center
- University Hospitals Cleveland Medical Center
- Oregon Health & Science University Hospital
- PinnacleHealth Cardiovascular Institute
- Hospital of the University of Pennsylvania
- The Miriam Hospital
- AnMed Health
- Centennial Medical Center
- Baylor Heart & Vascular Hospital
- Charleston Area Medical Center
- Aurora St. Luke's Medical Center
- Alfred Hospital
- St. George Hospital
- Royal Perth
- Klinikum Wels-Grieskirchen
- St. Michael's Hospital
- Clinique Pasteur
- Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH
- Universitätsklinikum Erlangen
- Universitätsklinikum des Saarlandes
- Herzzentrum Leipzig, Universitätsklinik
- Sana Kliniken Lübeck
- Hippokration General Hospital of Athens
- University General Hospital of Thessaloniki (AHEPA)
- Galway University Hospital
- Higashi Takarazuka Satoh Hospital
- Shonan Kamakura General Hospital
- Jichi Medical University Hospital
- Mitsui Memorial Hospital
- Saiseikai Nakatsu Hospital
- Royal Bournemouth Hospital
- Cardiff and Vale University Health Board - University Hospital of Wales
- Royal Devon & Exeter NHS Foundation Trust
- Imperial College Healthcare NHS Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Renal Denervation
Sham Procedure
Arm Description
Renal angiography and Renal Denervation (Symplicity Spyral™ multi-electrode renal denervation system)
Renal angiography
Outcomes
Primary Outcome Measures
Acute and Chronic Safety by Evaluating Incidence of Major Adverse Events
The primary safety endpoint of the study is the incidence of Major Adverse Events (MAE), defined as a composite of the following 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%, confirmed by angiography and as a determined by the angiographic core laboratory, through one-month post-randomization (6- months for new renal artery stenosis).
Change in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM)
Baseline adjusted change (using Analysis of Covariance) in systolic blood pressure (SBP) from baseline (Screening Visit 2) to 6 months post-procedure as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM).
Secondary Outcome Measures
Change in Office Systolic Blood Pressure
Change in office systolic blood pressure from baseline (Screening Visit 2) to 6 months post-procedure
Antihypertensive Medication Usage and Changes to 6-months
Number of medications from baseline (Screening Visit 2) through 6 Months post-procedure
Antihypertensive Medication Burden to 6-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.
Minimum value 0; No Maximum value
Medication Changes
Patients who had medication changes based on Medication Index 2 drug testing data. Medication Index 2 score 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.
Incidence of Achieving Target Office Systolic Blood Pressure
Incidence of achieving target office systolic blood pressure (SBP<140 mmHg) at 6 months post- procedure.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02439775
Brief Title
SPYRAL HTN-ON MED Study
Official Title
Global Clinical Study of Renal Denervation With the Symplicity Spyral™ Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension on Standard Medical Therapy (SPYRAL HTN-ON MED)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 2015 (Actual)
Primary Completion Date
August 18, 2022 (Actual)
Study Completion Date
October 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medtronic Vascular
4. Oversight
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes
5. Study Description
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 presence of up to three standard antihypertensive medications.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Vascular Diseases, Cardiovascular Diseases
Keywords
Uncontrolled hypertension, Renal denervation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
337 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Renal Denervation
Arm Type
Experimental
Arm Description
Renal angiography and Renal Denervation (Symplicity Spyral™ multi-electrode renal denervation system)
Arm Title
Sham Procedure
Arm Type
Sham Comparator
Arm Description
Renal angiography
Intervention Type
Device
Intervention Name(s)
Symplicity Spyral™ multi-electrode renal denervation system
Other Intervention Name(s)
Renal angiography, Renal Denervation
Intervention Description
After a renal angiography according to standard procedures, subjects remain blinded and are immediately treated with the renal denervation procedure after randomization.
Intervention Type
Procedure
Intervention Name(s)
Sham Procedure
Other Intervention Name(s)
Renal angiography
Intervention Description
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.
Primary Outcome Measure Information:
Title
Acute and Chronic Safety by Evaluating Incidence of Major Adverse Events
Description
The primary safety endpoint of the study is the incidence of Major Adverse Events (MAE), defined as a composite of the following 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%, confirmed by angiography and as a determined by the angiographic core laboratory, through one-month post-randomization (6- months for new renal artery stenosis).
Time Frame
From baseline to 1 month post-procedure (6 months for new renal artery stenosis)
Title
Change in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM)
Description
Baseline adjusted change (using Analysis of Covariance) in systolic blood pressure (SBP) from baseline (Screening Visit 2) to 6 months post-procedure as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM).
Time Frame
From baseline to 6 months post-procedure
Secondary Outcome Measure Information:
Title
Change in Office Systolic Blood Pressure
Description
Change in office systolic blood pressure from baseline (Screening Visit 2) to 6 months post-procedure
Time Frame
From baseline to 6 months post-procedure
Title
Antihypertensive Medication Usage and Changes to 6-months
Description
Number of medications from baseline (Screening Visit 2) through 6 Months post-procedure
Time Frame
From baseline to 6-month post-procedure
Title
Antihypertensive Medication Burden to 6-months
Description
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.
Minimum value 0; No Maximum value
Time Frame
From baseline to 6 Months post-procedure
Title
Medication Changes
Description
Patients who had medication changes based on Medication Index 2 drug testing data. Medication Index 2 score 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.
Time Frame
Baseline to 6-months post-procedure
Title
Incidence of Achieving Target Office Systolic Blood Pressure
Description
Incidence of achieving target office systolic blood pressure (SBP<140 mmHg) at 6 months post- procedure.
Time Frame
From baseline to 6 months post-procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Individual has office systolic blood pressure (SBP) ≥ 150 mmHg and <180 mmHg and a diastolic blood pressure (DBP) ≥ 90 mmHg when receiving a medication regimen of one, two, or three antihypertensive medication classes.
Individual has 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average SBP ≥ 140 mmHg and < 170 mmHg.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raymond Townsend, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Kandzari, MD
Organizational Affiliation
Piedmont Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Böhm, MD
Organizational Affiliation
Universitätskliniken des Saarlandes
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kazuomi Kario, MD
Organizational Affiliation
Jichi Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Heart Center Research, LLC
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
Facility Name
Stanford Hospital and Clinics
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Washington DC VA Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
Baptist Medical Center Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Memorial Hospital Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Tallahassee Research Institute
City
Tallahassee
State/Province
Florida
ZIP/Postal Code
32308
Country
United States
Facility Name
Emory University Hospital Midtown
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Piedmont Heart Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Iowa Heart Center
City
West Des Moines
State/Province
Iowa
ZIP/Postal Code
50266
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
St Joseph Mercy Oakland
City
Pontiac
State/Province
Michigan
ZIP/Postal Code
48341
Country
United States
Facility Name
Providence Hospital
City
Southfield
State/Province
Michigan
ZIP/Postal Code
48075
Country
United States
Facility Name
Minneapolis Heart Institute Foundation
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Hattiesburg Clinic
City
Hattiesburg
State/Province
Mississippi
ZIP/Postal Code
39401
Country
United States
Facility Name
Cardiology Associates Research LLC
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Saint Barnabas Medical Center
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
Facility Name
North Shore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Weill Cornell Medical College/The New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Oregon Health & Science University Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
PinnacleHealth Cardiovascular Institute
City
Harrisburg
State/Province
Pennsylvania
ZIP/Postal Code
17011
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
The Miriam Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
AnMed Health
City
Anderson
State/Province
South Carolina
ZIP/Postal Code
29621
Country
United States
Facility Name
Centennial Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Baylor Heart & Vascular Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75226
Country
United States
Facility Name
Charleston Area Medical Center
City
Charleston
State/Province
West Virginia
ZIP/Postal Code
25304
Country
United States
Facility Name
Aurora St. Luke's Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
St. George Hospital
City
Kogarah
Country
Australia
Facility Name
Royal Perth
City
Perth
Country
Australia
Facility Name
Klinikum Wels-Grieskirchen
City
Wels
ZIP/Postal Code
4600
Country
Austria
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Clinique Pasteur
City
Toulouse
Country
France
Facility Name
Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH
City
Bad Krozingen
ZIP/Postal Code
79189
Country
Germany
Facility Name
Universitätsklinikum Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Universitätsklinikum des Saarlandes
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Facility Name
Herzzentrum Leipzig, Universitätsklinik
City
Leipzig
ZIP/Postal Code
04289
Country
Germany
Facility Name
Sana Kliniken Lübeck
City
Lübeck
ZIP/Postal Code
23560
Country
Germany
Facility Name
Hippokration General Hospital of Athens
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
University General Hospital of Thessaloniki (AHEPA)
City
Thessaloniki
ZIP/Postal Code
54621
Country
Greece
Facility Name
Galway University Hospital
City
Galway
Country
Ireland
Facility Name
Higashi Takarazuka Satoh Hospital
City
Takarazuka
State/Province
Hyogo
Country
Japan
Facility Name
Shonan Kamakura General Hospital
City
Kamakura City
State/Province
Okamoto
Country
Japan
Facility Name
Jichi Medical University Hospital
City
Shimotsuke
State/Province
Tochigi
ZIP/Postal Code
329-0498
Country
Japan
Facility Name
Mitsui Memorial Hospital
City
Chiyoda
State/Province
Tokyo
ZIP/Postal Code
101-8643
Country
Japan
Facility Name
Saiseikai Nakatsu Hospital
City
Osaka
Country
Japan
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
Country
United Kingdom
Facility Name
Cardiff and Vale University Health Board - University Hospital of Wales
City
Cardiff
Country
United Kingdom
Facility Name
Royal Devon & Exeter NHS Foundation Trust
City
Exeter
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
Imperial College Healthcare NHS Trust
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
35390320
Citation
Mahfoud F, Kandzari DE, Kario K, Townsend RR, Weber MA, Schmieder RE, Tsioufis K, Pocock S, Dimitriadis K, Choi JW, East C, D'Souza R, Sharp ASP, Ewen S, Walton A, Hopper I, Brar S, McKenna P, Fahy M, Bohm M. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet. 2022 Apr 9;399(10333):1401-1410. doi: 10.1016/S0140-6736(22)00455-X. Epub 2022 Apr 4.
Results Reference
derived
PubMed Identifier
33226002
Citation
Kandzari DE, Hickey GL, Pocock SJ, Weber MA, Bohm M, Cohen SA, Fahy M, Lamberti G, Mahfoud F. Prioritised endpoints for device-based hypertension trials: the win ratio methodology. EuroIntervention. 2021 Apr 2;16(18):e1496-e1502. doi: 10.4244/EIJ-D-20-01090.
Results Reference
derived
PubMed Identifier
32740754
Citation
Kario K, Weber MA, Bohm M, Townsend RR, Mahfoud F, Schmieder RE, Tsioufis K, Cohen SA, Fahy M, Kandzari DE. Effect of renal denervation in attenuating the stress of morning surge in blood pressure: post-hoc analysis from the SPYRAL HTN-ON MED trial. Clin Res Cardiol. 2021 May;110(5):725-731. doi: 10.1007/s00392-020-01718-6. Epub 2020 Aug 1.
Results Reference
derived
PubMed Identifier
32034481
Citation
Bohm M, Townsend RR, Kario K, Kandzari D, Mahfoud F, Weber MA, Schmieder RE, Tsioufis K, Hickey GL, Fahy M, DeBruin V, Brar S, Pocock S. Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clin Res Cardiol. 2020 Mar;109(3):289-302. doi: 10.1007/s00392-020-01595-z. Epub 2020 Feb 7. Erratum In: Clin Res Cardiol. 2020 May;109(5):653.
Results Reference
derived
PubMed Identifier
29803589
Citation
Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, Tsioufis K, Tousoulis D, Choi JW, East C, Brar S, Cohen SA, Fahy M, Pilcher G, Kario K; SPYRAL HTN-ON MED Trial Investigators. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018 Jun 9;391(10137):2346-2355. doi: 10.1016/S0140-6736(18)30951-6. Epub 2018 May 23.
Results Reference
derived
PubMed Identifier
26699604
Citation
Kandzari DE, Kario K, Mahfoud F, Cohen SA, Pilcher G, Pocock S, Townsend R, Weber MA, Bohm M. The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. Am Heart J. 2016 Jan;171(1):82-91. doi: 10.1016/j.ahj.2015.08.021. Epub 2015 Sep 11.
Results Reference
derived
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SPYRAL HTN-ON MED Study
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