SPYRAL HTN-ON MED Study of Renal Denervation With the Symplicity Spyral™ Multi-electrode Renal Denervation System

NCT02439775 | Completed Results DMC FDA Device

• 1 other identifier: SPYRAL HTN-ON MED
• Study Type: interventional
• Target: 337
• Locations: 9 countries
• Sites: 55

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.

Conditions

Hypertension; Vascular Diseases; Cardiovascular Diseases

Keywords

Uncontrolled hypertension; Renal denervation

Outcome Measures

Primary Outcomes (2)

• 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).

  From baseline to 1 month post-procedure (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).

  From baseline to 6 months post-procedure

Secondary Outcomes (5)

• Change in Office Systolic Blood Pressure

  From baseline to 6 months post-procedure

• Antihypertensive Medication Usage and Changes to 6-months

  From baseline to 6-month post-procedure

• Antihypertensive Medication Burden to 6-months

  From baseline to 6 Months post-procedure

• Medication Changes

  Baseline to 6-months post-procedure

• Incidence of Achieving Target Office Systolic Blood Pressure

  From baseline to 6 months post-procedure

Study Arms (2)

Renal Denervation

EXPERIMENTAL

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

Device: Symplicity Spyral™ multi-electrode renal denervation system

Sham Procedure

SHAM COMPARATOR

Renal angiography

Procedure: Sham Procedure

Interventions

Symplicity Spyral™ multi-electrode renal denervation system DEVICE

After a renal angiography according to standard procedures, subjects remain blinded and are immediately treated with the renal denervation procedure after randomization.

Also known as: Renal angiography, Renal Denervation

Renal Denervation

Sham Procedure 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.

Also known as: Renal angiography

Sham Procedure

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medtronic Vascular: lead

Study Sites (56)

Heart Center Research, LLC

Huntsville, Alabama, 35801, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Washington DC VA Medical Center

Washington D.C., District of Columbia, 20422, United States

Location

Baptist Medical Center Jacksonville

Jacksonville, Florida, 32207, United States

Location

Memorial Hospital Jacksonville

Jacksonville, Florida, 32216, United States

Location

Tallahassee Research Institute

Tallahassee, Florida, 32308, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Piedmont Heart Institute

Atlanta, Georgia, 30309, United States

Location

Iowa Heart Center

West Des Moines, Iowa, 50266, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

St Joseph Mercy Oakland

Pontiac, Michigan, 48341, United States

Location

Providence Hospital

Southfield, Michigan, 48075, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

Cardiology Associates Research LLC

Tupelo, Mississippi, 38801, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Weill Cornell Medical College/The New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Oregon Health & Science University Hospital

Portland, Oregon, 97239, United States

Location

PinnacleHealth Cardiovascular Institute

Harrisburg, Pennsylvania, 17011, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

AnMed Health

Anderson, South Carolina, 29621, United States

Location

Centennial Medical Center

Nashville, Tennessee, 37203, United States

Location

Baylor Heart & Vascular Hospital

Dallas, Texas, 75226, United States

Location

Charleston Area Medical Center

Charleston, West Virginia, 25304, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

St. George Hospital

Kogarah, Australia

Location

Royal Perth

Perth, Australia

Location

Klinikum Wels-Grieskirchen

Wels, 4600, Austria

Location

Hamilton Heath

Hamilton, Ontario, Canada

Location

St. Michael's Hospital

Toronto, Ontario, Canada

Location

Clinique Pasteur

Toulouse, France

Location

Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH

Bad Krozingen, 79189, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Herzzentrum Leipzig, Universitätsklinik

Leipzig, 04289, Germany

Location

Sana Kliniken Lübeck

Lübeck, 23560, Germany

Location

Hippokration General Hospital of Athens

Athens, 11527, Greece

Location

University General Hospital of Thessaloniki (AHEPA)

Thessaloniki, 54621, Greece

Location

Galway University Hospital

Galway, Ireland

Location

Higashi Takarazuka Satoh Hospital

Takarazuka, Hyōgo, Japan

Location

Shonan Kamakura General Hospital

Kamakura, Okamoto, Japan

Location

Jichi Medical University Hospital

Shimotsuke, Tochigi, 329-0498, Japan

Location

Mitsui Memorial Hospital

Chiyoda City, Tokyo, 101-8643, Japan

Location

Saiseikai Nakatsu Hospital

Osaka, Japan

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Cardiff and Vale University Health Board - University Hospital of Wales

Cardiff, United Kingdom

Location

Royal Devon & Exeter NHS Foundation Trust

Exeter, EX2 5DW, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Related Publications (9)

• Kandzari DE, Mahfoud F, Townsend RR, Kario K, Weber MA, Schmieder RE, Tsioufis K, Pocock S, Liu M, DeBruin V, Brar S, Bohm M. Long-Term Safety and Efficacy of Renal Denervation: 24-Month Results From the SPYRAL HTN-ON MED Trial. Circ Cardiovasc Interv. 2025 Jul;18(7):e015194. doi: 10.1161/CIRCINTERVENTIONS.125.015194. Epub 2025 May 20.

  PMID: 40391448 DERIVED

• Townsend RR, Ferdinand KC, Kandzari DE, Kario K, Mahfoud F, Weber MA, Schmieder RE, Pocock S, Tsioufis K, David S, Steigerwalt S, Walton A, Hopper I, Bertolet B, Sharif F, Fengler K, Fahy M, Hettrick DA, Brar S, Bohm M. Impact of Antihypertensive Medication Changes After Renal Denervation Among Different Patient Groups: SPYRAL HTN-ON MED. Hypertension. 2024 May;81(5):1095-1105. doi: 10.1161/HYPERTENSIONAHA.123.22251. Epub 2024 Feb 5.

  PMID: 38314554 DERIVED

• Kandzari DE, Townsend RR, Kario K, Mahfoud F, Weber MA, Schmieder RE, Pocock S, Tsioufis K, Konstantinidis D, Choi J, East C, Lauder L, Cohen DL, Kobayashi T, Schmid A, Lee DP, Ma A, Weil J, Agdirlioglu T, Schlaich MP, Shetty S, Devireddy CM, Lea J, Aoki J, Sharp ASP, Anderson R, Fahy M, DeBruin V, Brar S, Bohm M; SPYRAL HTN-ON MED Investigators. Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications. J Am Coll Cardiol. 2023 Nov 7;82(19):1809-1823. doi: 10.1016/j.jacc.2023.08.045.

  PMID: 37914510 DERIVED

• 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.

  PMID: 35390320 DERIVED

• 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.

  PMID: 33226002 DERIVED

• 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.

  PMID: 32740754 DERIVED

• 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.

  PMID: 32034481 DERIVED

• 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.

  PMID: 29803589 DERIVED

• 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.

  PMID: 26699604 DERIVED

MeSH Terms

Conditions

Hypertension; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Elishea Argent, Sr. Clinical Research Specialist
• Organization: Medtronic

elishea.n.argent@medtronic.com

(763)505-9584

Study Officials

• Raymond Townsend, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• David Kandzari, MD

  Piedmont Hospital

  PRINCIPAL INVESTIGATOR

• Michael Böhm, MD

  Universitätskliniken des Saarlandes

  PRINCIPAL INVESTIGATOR

• Kazuomi Kario, MD

  Jichi Medical University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2015
• First Posted: May 12, 2015
• Study Start: July 22, 2015
• Primary Completion: August 18, 2022
• Study Completion: August 14, 2025
• Last Updated: November 14, 2025
• Results First Posted: September 15, 2023

Record last verified: 2025-10

Locations

AU (3); IE (1); GB (4); US (32); CA (2); FR (1); GR (2); JP (5); DE (5)