SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study

NCT ID: NCT02439749

Last Updated: 2025-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 366 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2023-10-25

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Renal Denervation

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

Group Type: EXPERIMENTAL

Symplicity Spyral™ multi-electrode renal denervation system

Intervention Type: DEVICE

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

Sham Procedure

Renal angiography

Group Type: SHAM_COMPARATOR

Sham Procedure

Intervention Type: 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.

Interventions

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.

Intervention Type: DEVICE

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 Type: PROCEDURE

Other Intervention Names

Renal angiography; Renal Denervation; Renal angiography

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic Vascular

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raymond Townsend, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

David Kandzari, MD

Role: PRINCIPAL_INVESTIGATOR

Piedmont Hospital

Michael Böhm, MD

Role: PRINCIPAL_INVESTIGATOR

Universitätskliniken des Saarlandes

Kazuomi Kario, MD

Role: PRINCIPAL_INVESTIGATOR

Jichi Medical University

Locations

Heart Center Research, LLC

Huntsville, Alabama, United States

Honor Health Research Institute

Scottsdale, Arizona, United States

Kaiser Permanente LA Medical Center

Los Angeles, California, United States

Stanford Hospital and Clinics

Stanford, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Baptist Medical Center Jacksonville

Jacksonville, Florida, United States

Tallahassee Research Institute

Tallahassee, Florida, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Piedmont Heart Institute

Atlanta, Georgia, United States

Iowa Heart Center

West Des Moines, Iowa, United States

University of Kentucky

Lexington, Kentucky, United States

St Joseph Mercy Oakland

Pontiac, Michigan, United States

Providence Hospital

Southfield, Michigan, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Hattiesburg Clinic

Hattiesburg, Mississippi, United States

Cardiology Associates Research LLC

Tupelo, Mississippi, United States

Barnes-Jewish Hospital

St Louis, Missouri, United States

Saint Barnabas Medical Center

Livingston, New Jersey, United States

North Shore University Hospital

Manhasset, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

PinnacleHealth Cardiovascular Institute

Harrisburg, Pennsylvania, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

The Miriam Hospital

Providence, Rhode Island, United States

AnMed Health

Anderson, South Carolina, United States

Centennial Medical Center

Nashville, Tennessee, United States

Baylor Heart & Vascular Hospital

Dallas, Texas, United States

Charleston Area Medical Center

Charleston, West Virginia, United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Alfred Hospital

Melbourne, Victoria, Australia

Klinikum Wels-Grieskirchen

Wels, , Austria

St. Michael's Hospital

Toronto, Ontario, Canada

Institut de cardiologie de Montréal / Montreal Heart Institute

Montreal, Quebec, Canada

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, , Germany

Hippokration General Hospital of Athens

Athens, , Greece

University General Hospital of Thessaloniki (AHEPA)

Thessaloniki, , Greece

Galway University Hospital

Galway, , Ireland

Jichi Medical University Hospital

Shimotsuke, Tochigi, Japan

Mitsui Memorial Hospital

Chiyoda City, Tokyo, Japan

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 Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 35852582 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34474735 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33957242 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32234534 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32034481 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28859944 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26699604 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SPYRAL HTN-OFF MED

Identifier Type: -

Identifier Source: org_study_id