Clinical trial NCT02439749: SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study
Official title: Global Clinical Study of Renal Denervation With the Symplicity Spyral™ Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Vascular Diseases
Cardiovascular Diseases
Keywords: Uncontrolled hypertension
Renal denervation
Lead sponsor: Medtronic Vascular
Sponsor class: INDUSTRY
First posted: 2015-05-12
Enrollment: 366
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Major Adverse Events (MAE) Defined as a Composite of Events.
timeFrame: From baseline to 1 month post-procedure (6 months for new renal artery stenosis)
measure: Baseline Adjusted Change (Using Analysis of Covariance) in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring
timeFrame: From baseline to 3 months post-procedure
Secondary outcomes:
measure: Number of Participants With Significant Embolic Event Resulting in End-organ Damage
timeFrame: From baseline to 1 month post-procedure
measure: Number of Participants With Renal Artery Perforation Requiring Intervention
timeFrame: From baseline to 1 month post-procedure
measure: Renal Artery Dissection
timeFrame: From baseline to 1 month post-procedure
measure: Number of Participants With Vascular Complications
timeFrame: From baseline to 1 month post-procedure
measure: Number of Participants With End-stage Renal Disease
timeFrame: From baseline to 1 month post-procedure
measure: Number of Participants With Decline in eGFR
timeFrame: From baseline to 1 month post-procedure
measure: Myocardial Infarction
timeFrame: From baseline to 1 month post-procedure
measure: New Stroke
timeFrame: From baseline to 1 month post-procedure
measure: Number of Participants With Renal Artery Re-intervention
timeFrame: From baseline to 1 month post-procedure
measure: Number of Participants With Major Bleeding According to TIMI Definition
timeFrame: From baseline to 1 month post-procedure
measure: Number of Participants With Increase in Serum Creatinine
timeFrame: From baseline to 1 month post-procedure
measure: Number of Participants With Hospitalization for Hypertensive Crisis With Medications or the Protocol
timeFrame: From baseline to 1 month post-procedure
measure: Change in Office Systolic Blood Pressure
timeFrame: From baseline to 1 month post procedure
measure: Change in Office Diastolic Blood Pressure
timeFrame: From baseline to 1 month post procedure
measure: Number of Participants Achieving Target Office Systolic Blood Pressure
timeFrame: From baseline to 1 month post procedure
measure: Baseline Adjusted Change (Using Analysis of Covariance) in Office Systolic Blood Pressure
timeFrame: From baseline to 3 months post-procedure
measure: Number of Participants With All-cause Mortality
timeFrame: From baseline to 3 months post-procedure
measure: Number of Participants With ≥40% Decline in eGFR
timeFrame: From baseline to 3 months post randomization
measure: Number of Participants With End-Stage Renal Disease (ESRD)
timeFrame: From baseline to 3 months post randomization
measure: Number of Participants With New Myocardial Infarction
timeFrame: From baseline to 3 months post randomization
measure: New Stroke
timeFrame: From baseline to 3 months post randomization
measure: Number of Participants With Renal Artery Re-intervention
timeFrame: From baseline to 3 months post randomization
measure: Number of Participants With Major Bleeding According to TIMI Definition
timeFrame: From baseline to 3 months post randomization
measure: Increase in Serum Creatinine
timeFrame: From baseline to 3 months post randomization
measure: Number of Participants With Hospitalization for Hypertensive Crisis
timeFrame: From baseline to 3 months post randomization
measure: Change in Diastolic Blood Pressure as Measured by 24-hour ABPM
timeFrame: From baseline to 3 months post procedure
measure: Change in Office Diastolic Blood Pressure
timeFrame: From baseline to 3 months post procedure
measure: Number of Participants Achieving Target Office Systolic Blood Pressure
timeFrame: From baseline to 3 months post procedure
measure: Number of Participants With New Renal Artery Stenosis > 70%
timeFrame: From baseline to 6 month post-procedure
measure: Change in Systolic Blood Pressure as Measured by 24-hour ABPM
timeFrame: From baseline to 36 month post-procedure
measure: Change in Diastolic Blood Pressure as Measured by 24-hour ABPM
timeFrame: From baseline to 36 months post-procedure
measure: Change in Office Systolic Blood Pressure
timeFrame: From baseline to 36 months post procedure
measure: Change in Office Diastolic Blood Pressure
timeFrame: From baseline to 36 months post-procedure
measure: Number of Participants With Incidence of Achieving Target Office Systolic Blood Pressure (SBP <140) mmHg)
timeFrame: From baseline to 36 months post-procedure
measure: Number of Participants With All-cause Mortality
timeFrame: From baseline to 36 months post-randomization
measure: Number of Participants With End-Stage Renal Disease (ESRD)
timeFrame: From baseline to 36 months post randomization
measure: Number of Participants With ≥40% Decline in eGFR
timeFrame: From baseline to 36 months post randomization
measure: Number of Participants With New Myocardial Infarction
timeFrame: From baseline to 36 months post randomization
measure: Number of Participants With New Stroke
timeFrame: From baseline to 36 months post randomization
measure: Number of Participants With Renal Artery Re-intervention
timeFrame: From baseline to 36 months post randomization
measure: Number of Participants With Major Bleeding According to TIMI Definition
timeFrame: From baseline to 36 months post randomization
measure: Number of Participants With an Increase in Serum Creatinine
timeFrame: From baseline to 36 months post randomization
measure: Number of Participants With New Renal Artery Stenosis > 70%
timeFrame: From baseline to 36 months post randomization
measure: Number of Participants With Hospitalization for Hypertensive Crisis
timeFrame: From baseline to 36 months post randomization
Other outcomes:
measure: Antihypertensive Medication Burden to 36-months
timeFrame: From baseline to 36 months post-procedure
Locations:
city: Huntsville
country: United States
facility: Heart Center Research, LLC
state: Alabama
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Los Angeles
country: United States
facility: Kaiser Permanente LA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Jacksonville
country: United States
facility: Baptist Medical Center Jacksonville
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: West Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Pontiac
country: United States
facility: St Joseph Mercy Oakland
state: Michigan
city: Southfield
country: United States
facility: Providence Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Tupelo
country: United States
facility: Cardiology Associates Research LLC
state: Mississippi
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Harrisburg
country: United States
facility: PinnacleHealth Cardiovascular Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Anderson
country: United States
facility: AnMed Health
state: South Carolina
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Heart & Vascular Hospital
state: Texas
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montréal
country: Canada
facility: Institut de cardiologie de Montréal / Montreal Heart Institute
state: Quebec
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig, Universitätsklinik
city: Lübeck
country: Germany
facility: Sana Kliniken Lübeck
city: Athens
country: Greece
facility: Hippokration General Hospital of Athens
city: Thessaloniki
country: Greece
facility: University General Hospital of Thessaloniki (AHEPA)
city: Galway
country: Ireland
facility: Galway University Hospital
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Chiyoda
country: Japan
facility: Mitsui Memorial Hospital
state: Tokyo
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Health Board - University Hospital of Wales
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: University of Pennsylvania
name: Raymond Townsend, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Piedmont Hospital
name: David Kandzari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätskliniken des Saarlandes
name: Michael Böhm, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jichi Medical University
name: Kazuomi Kario, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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.
citation: 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.
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.