SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study

NCT02439749 | Completed Results DMC FDA Device

• 1 other identifier: SPYRAL HTN-OFF MED
• Study Type: interventional
• Target: 366
• Locations: 8 countries
• Sites: 46

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.

Conditions

Hypertension; Vascular Diseases; Cardiovascular Diseases

Keywords

Uncontrolled hypertension; Renal denervation

Outcome Measures

Primary Outcomes (2)

• 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)

  From baseline to 1 month post-procedure (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 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 Outcomes (44)

• Number of Participants With Significant Embolic Event Resulting in End-organ Damage

  From baseline to 1 month post-procedure

• Number of Participants With Renal Artery Perforation Requiring Intervention

  From baseline to 1 month post-procedure

• Renal Artery Dissection

  From baseline to 1 month post-procedure

• Number of Participants With Vascular Complications

  From baseline to 1 month post-procedure

• Number of Participants With End-stage Renal Disease

  From baseline to 1 month post-procedure

Other Outcomes (1)

• Antihypertensive Medication Burden to 36-months

  From baseline to 36 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 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.

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 (47)

Heart Center Research, LLC

Huntsville, Alabama, 35801, United States

Location

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

Kaiser Permanente LA Medical Center

Los Angeles, California, 90027, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Baptist Medical Center Jacksonville

Jacksonville, Florida, 32207, 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

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

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

Klinikum Wels-Grieskirchen

Wels, 4600, Austria

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Institut de cardiologie de Montréal / Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

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

Jichi Medical University Hospital

Shimotsuke, Tochigi, 329-0498, Japan

Location

Mitsui Memorial Hospital

Chiyoda City, Tokyo, 101-8643, Japan

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 (7)

• Weber MA, Schmieder RE, Kandzari DE, Townsend RR, Mahfoud F, Tsioufis K, Kario K, Pocock S, Tatakis F, Ewen S, Choi JW, East C, Lee DP, Ma A, Cohen DL, Wilensky R, Devireddy CM, Lea JP, Schmid A, Fahy M, Bohm M. Hypertension urgencies in the SPYRAL HTN-OFF MED Pivotal trial. Clin Res Cardiol. 2022 Nov;111(11):1269-1275. doi: 10.1007/s00392-022-02064-5. Epub 2022 Jul 19.

  PMID: 35852582 DERIVED

• Bohm M, Tsioufis K, Kandzari DE, Kario K, Weber MA, Schmieder RE, Townsend RR, Kulenthiran S, Ukena C, Pocock S, Ewen S, Weil J, Fahy M, Mahfoud F. Effect of Heart Rate on the Outcome of Renal Denervation in Patients With Uncontrolled Hypertension. J Am Coll Cardiol. 2021 Sep 7;78(10):1028-1038. doi: 10.1016/j.jacc.2021.06.044.

  PMID: 34474735 DERIVED

• Mahfoud F, Townsend RR, Kandzari DE, Kario K, Schmieder RE, Tsioufis K, Pocock S, David S, Patel K, Rao A, Walton A, Bloom JE, Weber T, Suppan M, Lauder L, Cohen SA, McKenna P, Fahy M, Bohm M, Weber MA. Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation. J Am Coll Cardiol. 2021 Jun 15;77(23):2909-2919. doi: 10.1016/j.jacc.2021.04.044. Epub 2021 May 3.

  PMID: 33957242 DERIVED

• Bohm M, Kario K, Kandzari DE, Mahfoud F, Weber MA, Schmieder RE, Tsioufis K, Pocock S, Konstantinidis D, Choi JW, East C, Lee DP, Ma A, Ewen S, Cohen DL, Wilensky R, Devireddy CM, Lea J, Schmid A, Weil J, Agdirlioglu T, Reedus D, Jefferson BK, Reyes D, D'Souza R, Sharp ASP, Sharif F, Fahy M, DeBruin V, Cohen SA, Brar S, Townsend RR; SPYRAL HTN-OFF MED Pivotal Investigators. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020 May 2;395(10234):1444-1451. doi: 10.1016/S0140-6736(20)30554-7. Epub 2020 Mar 29.

  PMID: 32234534 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

• Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, Ewen S, Tsioufis K, Tousoulis D, Sharp ASP, Watkinson AF, Schmieder RE, Schmid A, Choi JW, East C, Walton A, Hopper I, Cohen DL, Wilensky R, Lee DP, Ma A, Devireddy CM, Lea JP, Lurz PC, Fengler K, Davies J, Chapman N, Cohen SA, DeBruin V, Fahy M, Jones DE, Rothman M, Bohm M; SPYRAL HTN-OFF MED trial investigators*. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017 Nov 11;390(10108):2160-2170. doi: 10.1016/S0140-6736(17)32281-X. Epub 2017 Aug 28.

  PMID: 28859944 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: Pamela McKenna, Sr. Principal Clinical Research Specialist
• Organization: Medtronic

pamela.m.mckenna@medtronic.com

(773) 597-5241

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: June 1, 2015
• Primary Completion: April 30, 2020
• Study Completion: October 25, 2023
• Last Updated: March 28, 2025
• Results First Posted: May 27, 2021

Record last verified: 2025-03

Locations

CA (2); GR (2); AU (1); US (30); IE (1); GB (3); DE (5); JP (2)