SPYRAL AFFIRM Global Study of RDN With the Symplicity Spyral RDN System in Subjects With Uncontrolled HTN

The SPYRAL AFFIRM Global Clinical Study of Renal Denervation With the Symplicity Spyral Renal Denervation System in Subjects With Uncontrolled Hypertension (SPYRAL AFFIRM)

The purpose of this single-arm interventional study is to evaluate the long-term safety, efficacy, and durability of the Symplicity Spyral system in subjects treated with renal denervation.

Additionally, long-term follow-up data will also be collected from eligible subjects previously treated in the SPYRAL PIVOTAL-SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED studies.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; Vascular Diseases; Hypertension; Diabetes Mellitus; Chronic Kidney Diseases
• Intervention / Treatment: Device: Renal Denervation (Symplicity Spyral™)

• Study Type: Interventional
• Enrollment (Actual): 1899
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital (Dobney Hypertension Centre)
• Belgium
  • Bruges, Belgium, 8000
    • AZ Sint Jan Brugge-Oostende av
  • Genk, Belgium, 3600
    • Ziekenhuis Oost Limburg - Campus Sint-Jan
  • Ghent, Belgium, 9000
    • University Hospital Ghent
  • Liège, Belgium, 4000
    • CHC MontLegia
  • Oost - Vlaanderen
    • Aalst, Oost - Vlaanderen, Belgium, 9300
      • Algemeen Stedelijk Ziekenhuis - R&D Hartziekten
• France
  • Bordeaux, France, 33 000
    • Hôpital Saint André -Centre Hospitalier Universitaire de Bordeaux
  • Paris, France, 75013
    • Hopital Pitie Salpetriere
• Germany
  • Erlangen, Germany, 91054
    • Uniklinik Erlangen
  • Giessen, Germany, 35390
    • Justus-Liebig-Universität Gießen
  • Homburg, Germany
    • Universitätsklinikum des Saarlandes
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig
  • Lübeck, Germany, 23560
    • Sana Kliniken Lübeck GmbH
• Greece
  • Athens, Greece, 11527
    • Hippokration General Hospital of Athens
• Ireland
  • Dublin, Ireland, D07 R2WY
    • Mater Misericordiae University Hospital
• Monaco
  • Monaco, Monaco, 98000
    • Centre Hospitalier Princesse Grace
• Netherlands
  • Heerlen, Netherlands, 6419 PC
    • Zuyderland Medisch Centrum Heerlen
  • Rotterdam, Netherlands
    • Erasmus Universtiy Medical Center
• Sweden
  • Stockholm, Sweden, 18288
    • Danderyd Sjukhus
• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • John Radcliffe Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham (UAB) Hospital
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Banner Heart Hospital
    • Phoenix, Arizona, United States, 85016
      • Abrazo Arizona Heart Hospital/Biltmore Cardiology
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cardiology
  • California
    • La Jolla, California, United States, 92037
      • Scripps Memorial Hospital
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • Stanford, California, United States, 94305
      • Stanford Hospital and Clinics
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
    • Lakewood, Colorado, United States, 80228
      • Colorado Heart and Vascular PC
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular Consultants
    • Clearwater, Florida, United States, 33756
      • BayCare Health System
    • Jacksonville, Florida, United States, 32207
      • Baptist Medical Center
    • Miami, Florida, United States, 33136
      • University of Miami Hosptial
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
    • Orlando, Florida, United States, 32806
      • Orlando Health Heart & Vascular Institute
    • Safety Harbor, Florida, United States, 34695
      • BayCare Medical Group
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Healthcare, Inc
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
    • Marietta, Georgia, United States, 30060
      • Wellstar Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine
    • Maywood, Illinois, United States, 60153-3328
      • Loyola University Medical Center
    • Palos Park, Illinois, United States, 60464
      • Heart Care Centers of Illinois
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • St. Vincents Hospital
  • Iowa
    • West Des Moines, Iowa, United States, 50266-8209
      • Mercy Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
    • Towson, Maryland, United States, 21204
      • Saint Joseph Medical Center (Towson MD)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Henry Ford Saint John Hospital
    • Grand Rapids, Michigan, United States, 49503-2560
      • Spectrum Health Hospitals
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Southfield, Michigan, United States, 48075
      • Henry Ford Providence Southfield Hospital
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Metropolitan Heart and Vascular Institute (MHVI)
    • Saint Cloud, Minnesota, United States, 56303-1900
      • CentraCare Heart & Vascular Center
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Virtua Medical Group
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Neptune City, New Jersey, United States, 07753
      • Jersey Shore University Medical Center
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital
  • New York
    • Liverpool, New York, United States, 13088
      • SJH Cardiology Associates
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10021-9800
      • Weill Cornell Medical Center
    • Roslyn, New York, United States, 11576-1348
      • Saint Francis Hospital
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Sanford Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Cl inic
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Heart Hospital
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17101
      • UPMC Harrisburg Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Rhode Island Hospital and Health Services
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Centennial Medical Center
  • Texas
    • Dallas, Texas, United States, 75226-1316
      • Baylor Jack and Jane Hamilton Heart and Vascular Hospital
    • Edinburg, Texas, United States, 78539
      • DHR Health Institute for Research and Development
    • Houston, Texas, United States, 77030
      • Houston Methodist
    • Plano, Texas, United States, 75093
      • Baylor Scott & White The Heart Hospital Baylor Plano
    • San Antonio, Texas, United States, 78229
      • Methodist Hospital
    • Tyler, Texas, United States, 75701
      • The University of Texas at Tyler
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • UVA Medical Center
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center Everett
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Advocate Aurora Health-Aurora St. Luke's Medical Center (ASLMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Individual is diagnosed with hypertension and has a baseline office systolic blood pressure ≥140 mmHg
2. Individual has a baseline office diastolic blood pressure ≥ 90 mmHg
3. Individual has an average systolic baseline home blood pressure ≥135 mmHg

Exclusion Criteria:

1. Individual lacks appropriate renal artery anatomy
2. Individual has undergone prior renal denervation
3. Individual has a documented condition that would prohibit or interfere with ability to obtain an accurate blood pressure measurement
4. Individual requires chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea
5. Individual has an estimated glomerular filtration rate (eGFR) of <45
6. Individual has one or more episode(s) of orthostatic hypotension
7. Individual is pregnant, nursing or planning to become pregnant
8. Individual has primary pulmonary hypertension
9. Individual has documented type 1 diabetes mellitus or poorly-controlled type 2 diabetes mellitus with glycosylated hemoglobin greater than 8.0%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Main Cohort: Renal Denervation; Renal angiography and Renal Denervation (Symplicity Spyral™ multi-electrode renal denervation system)	Device: Renal Denervation (Symplicity Spyral™); Device: Symplicity Spyral™ multi-electrode renal denervation system. After a renal angiography according to standard procedures, subjects are treated with the renal denervation procedure.; Other Names: Renal Denervation; Renal Angiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary endpoint of office Systolic Blood Pressure (SBP) change at 6 months.	The Primary endpoint of office Systolic Blood Pressure (SBP) change at 6 months will be assessed for all patients in the Main Study Cohort	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Office Systolic Blood Pressure change	From baseline to 3, 6, 12, 24, and 36 months post-procedure
Home Blood Pressure change (Main Cohort Only)	From baseline to 3, 6, 12, 24, and 36 months post-procedure
Change in blood pressure as measured by 24-hour ABPM	From baseline to 3, 6, 12, 24, and 36 months post-procedure
Time subject's blood pressure is controlled	Procedure to 36 months post-procedure
Change in number of anti-hypertensive medications taken from baseline	From baseline to 3, 6, 12, 24, and 36 months post-procedure
Change from baseline in EQ-5D quality of life score	From baseline to 3, 6, 12, 24, and 36 months post-procedure
Change from baseline in hypertension health status score	From baseline to 3, 6, 12, 24, and 36 months post-procedure
Evaluate pre-specified subgroups (Chronic Kidney Disease, Diabetes Mellitus Type II, etc) as predictors for change in blood pressure as measured by OBP, HBP and ABPM	From baseline to 3, 6, 12, 24, and 36 months post-procedure
Evaluation of slope of eGFR	From baseline to 3, 6, 12, 24, and 36 months post-procedure
Percent of subjects achieving blood pressure control as measured by OBP, HBP and ABPM	From baseline to 3, 6, 12, 24, and 36 months post-procedure
Incidence of events, including major adverse events	From baseline to 3, 6, 12, 24, and 36 months post-procedure

Collaborators and Investigators

• Sponsor: Medtronic Vascular
• Investigators: Principal Investigator: David Kandzari, MD, Piedmont Heart Institute; Principal Investigator: Felix Mahfoud, MD, Saarland University Hospital

Publications and helpful links

General Publications

• Abid S, Mehta S, Munazzah F, Yager N, Baloch S, Hongalgi K. Renal Denervation: A New Era in the Management of Resistant Hypertension. Kidney360. 2025 Nov 1;6(11):2010-2016. doi: 10.34067/KID.0000000961. Epub 2025 Aug 13.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2029

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: January 6, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Glucose Metabolism Disorders; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Hypertension; Cardiovascular Diseases; Diabetes Mellitus; Vascular Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: MDT20044RDN004; SPYRAL SWFYT (NCT07115953) (Other Identifier: ClinicalTrials.gov)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No