Clinical trial NCT02439775: SPYRAL HTN-ON MED Study of Renal Denervation With the Symplicity Spyral™ Multi-electrode Renal Denervation System
Official title: Global Clinical Study of Renal Denervation With the Symplicity Spyral™ Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension on Standard Medical Therapy (SPYRAL HTN-ON MED)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
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: 337
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 presence of up to three standard antihypertensive medications.

Detailed description: The purpose of this study is to test the hypothesis that renal denervation is safe and reduces systolic blood pressure (SBP) in patients with uncontrolled hypertension on one, two, or three standard antihypertensive medications compared to a sham control in the same population. In this study, "uncontrolled hypertension" is defined as an office systolic blood pressure (SBP) ≥ 150 mmHg and \<180 mmHg, an office Diastolic Blood Pressure (DBP) ≥90 mmHg and a 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average SBP ≥140 mmHg to \<170 mmHg, all of which are measured at Screening Visits. Data obtained will be used to confirm the effect of renal denervation on elevated blood pressure in patients on 1, 2 or 3 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 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.

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: Acute and Chronic Safety by Evaluating Incidence of Major Adverse Events
timeFrame: From baseline to 1 month post-procedure (6 months for new renal artery stenosis)
measure: Change in Systolic Blood Pressure as Measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM)
timeFrame: From baseline to 6 months post-procedure
Secondary outcomes:
measure: Change in Office Systolic Blood Pressure
timeFrame: From baseline to 6 months post-procedure
measure: Antihypertensive Medication Usage and Changes to 6-months
timeFrame: From baseline to 6-month post-procedure
measure: Antihypertensive Medication Burden to 6-months
timeFrame: From baseline to 6 Months post-procedure
measure: Medication Changes
timeFrame: Baseline to 6-months post-procedure
measure: Incidence of Achieving Target Office Systolic Blood Pressure
timeFrame: From baseline to 6 months post-procedure
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Heart Center Research, LLC
state: Alabama
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: Washington
country: United States
facility: Washington DC VA Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Baptist Medical Center Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Memorial Hospital 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: Weill Cornell Medical College/The New York Presbyterian 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: Portland
country: United States
facility: Oregon Health & Science University Hospital
state: Oregon
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: Kogarah
country: Australia
facility: St. George Hospital
city: Perth
country: Australia
facility: Royal Perth
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen
city: Hamilton
country: Canada
facility: Hamilton Heath
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toulouse
country: France
facility: Clinique Pasteur
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: Takarazuka
country: Japan
facility: Higashi Takarazuka Satoh Hospital
state: Hyogo
city: Kamakura City
country: Japan
facility: Shonan Kamakura General Hospital
state: Okamoto
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Chiyoda
country: Japan
facility: Mitsui Memorial Hospital
state: Tokyo
city: Osaka
country: Japan
facility: Saiseikai Nakatsu Hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
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: 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.
citation: 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.
citation: 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.
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: 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.
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.