Clinical trial NCT01418261: SYMPLICITY HTN-3 Renal Denervation in Patients With Uncontrolled Hypertension
Official title: Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN-3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Uncontrolled Hypertension
Keywords: uncontrolled hypertension
renal denervation
Lead sponsor: Medtronic Vascular
Sponsor class: INDUSTRY
First posted: 2011-08-17
Enrollment: 535
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study of the safety and effectiveness of renal denervation in subjects with uncontrolled hypertension. Bilateral renal denervation will be performed using the Symplicity Catheter - a percutaneous system that delivers radiofrequency (RF)energy through the luminal surface of the renal artery.

Detailed description: The Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study of the safety and effectiveness of renal denervation in subjects with uncontrolled hypertension. Bilateral renal denervation will be performed using the Symplicity Catheter - a percutaneous system that delivers radiofrequency (RF)energy through the luminal surface of the renal artery.

Eligibility criteria: Inclusion Criteria:

* Individual is ≥ 18 and ≤ 80 years old at time of randomization.
* Individual is receiving a stable medication regimen including full tolerated doses of 3 or more anti-hypertensive medications of different classes, of which one must be a diuretic (with no changes for a minimum of 2 weeks prior to screening) that is expected to be maintained without changes for at least 6 months.
* Individual has an office systolic blood pressure (SBP) of ≥ 160 mmHg based on an average of 3 blood pressure readings measured at both an initial screening visit and a confirmatory screening visit

Exclusion Criteria:

* Individual has an estimated glomerular filtration rate (eGFR) of \< 45 mL/min/1.73 m2
* Individual has an Ambulatory Blood Pressure Monitoring (ABPM) 24 hour average SBP \< 135 mmHg
* Individual has type 1 diabetes mellitus
* Individual requires chronic oxygen support or mechanical ventilation (e.g., tracheostomy, CPAP, BiPAP) other than nocturnal respiratory support for sleep apnea.
* Individual has primary pulmonary hypertension.
* Individual is pregnant, nursing or planning to be pregnant.

Primary outcomes:
measure: Change in Office Systolic Blood Pressure
timeFrame: Baseline to 6 months post-randomization
Secondary outcomes:
measure: Change in average 24-hour Systolic Blood Pressure by ambulatory blood pressure monitoring
timeFrame: Baseline to 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology, PC
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: Scripps Clinic/Scripps Green Hospital
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente - Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: San Diego
country: United States
facility: San Diego Cardiac Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Washington, D.C.
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Washington, D.C.
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: Shands / University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: Miami
country: United States
facility: Baptist Cardiac &Vascular Institute, Baptist Health Systems
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
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: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Midwest Heart Foundation
state: Illinois
city: Springfield
country: United States
facility: Prairie Heart Institute
state: Illinois
city: Des Moines
country: United States
facility: Iowa Heart Center Research
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: VA Boston Healthcare System
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Harper University Hospital - Detroit Medical Center
state: Michigan
city: Pontiac
country: United States
facility: St Joseph Mercy Oakland Hospital
state: Michigan
city: Southfield
country: United States
facility: Providence Hospital
state: Michigan
city: Ypsilanti
country: United States
facility: Michigan Heart, St. Joseph Mercy Health System
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern/Minneapolis Heart Institute Foundation
state: Minnesota
city: Rochester
country: United States
facility: Saint Mary's Mayo Clinic
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic, P.A
state: Mississippi
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City/Mid America Heart Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Browns Mills
country: United States
facility: Deborah Heart & Lung Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Neptune City
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center-Manhattan
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital and Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Heart and Vascular
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Healthcare (SHVI)-Clinical Research
state: North Carolina
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Center for Research & Education at The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The MetroHealth System
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research Institute
state: Ohio
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospitals, Inc
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Vascular Disease Research Center at Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Stern Cardiovascular Foundation, Inc.
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Austin
country: United States
facility: Austin Heart PLLC / Heart Hospital of Austin
state: Texas
city: Dallas
country: United States
facility: VA North Texas Health Care System
state: Texas
city: Dallas
country: United States
facility: Soltero Cardiovascular Research Center - Baylor Jack and Jane Hamilton Heart & Vascular Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Professor of Medicine, Hypertension Center Director University of Chicago Medical Center
name: George Bakris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: VA Boston Healthcare System Department of Cardiology
name: Deepak L Bhatt, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bhatt DL, Vaduganathan M, Kandzari DE, Leon MB, Rocha-Singh K, Townsend RR, Katzen BT, Oparil S, Brar S, DeBruin V, Fahy M, Bakris GL; SYMPLICITY HTN-3 Steering Committee Investigators. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial. Lancet. 2022 Oct 22;400(10361):1405-1416. doi: 10.1016/S0140-6736(22)01787-1. Epub 2022 Sep 18.
citation: Mahfoud F, Bakris G, Bhatt DL, Esler M, Ewen S, Fahy M, Kandzari D, Kario K, Mancia G, Weber M, Bohm M. Reduced blood pressure-lowering effect of catheter-based renal denervation in patients with isolated systolic hypertension: data from SYMPLICITY HTN-3 and the Global SYMPLICITY Registry. Eur Heart J. 2017 Jan 7;38(2):93-100. doi: 10.1093/eurheartj/ehw325.
citation: Pocock SJ, Bakris G, Bhatt DL, Brar S, Fahy M, Gersh BJ. Regression to the Mean in SYMPLICITY HTN-3: Implications for Design and Reporting of Future Trials. J Am Coll Cardiol. 2016 Nov 1;68(18):2016-2025. doi: 10.1016/j.jacc.2016.07.775.
citation: Kario K, Bhatt DL, Brar S, Cohen SA, Fahy M, Bakris GL. Effect of Catheter-Based Renal Denervation on Morning and Nocturnal Blood Pressure: Insights From SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan. Hypertension. 2015 Dec;66(6):1130-7. doi: 10.1161/HYPERTENSIONAHA.115.06260. Epub 2015 Oct 5.
citation: Bakris GL, Townsend RR, Flack JM, Brar S, Cohen SA, D'Agostino R, Kandzari DE, Katzen BT, Leon MB, Mauri L, Negoita M, O'Neill WW, Oparil S, Rocha-Singh K, Bhatt DL; SYMPLICITY HTN-3 Investigators. 12-month blood pressure results of catheter-based renal artery denervation for resistant hypertension: the SYMPLICITY HTN-3 trial. J Am Coll Cardiol. 2015 Apr 7;65(13):1314-1321. doi: 10.1016/j.jacc.2015.01.037.
citation: Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, Flack JM, Katzen BT, Lea J, Lee DP, Leon MB, Ma A, Massaro J, Mauri L, Oparil S, O'Neill WW, Patel MR, Rocha-Singh K, Sobotka PA, Svetkey L, Townsend RR, Bakris GL. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J. 2015 Jan 21;36(4):219-27. doi: 10.1093/eurheartj/ehu441. Epub 2014 Nov 16.
citation: Bakris GL, Townsend RR, Liu M, Cohen SA, D'Agostino R, Flack JM, Kandzari DE, Katzen BT, Leon MB, Mauri L, Negoita M, O'Neill WW, Oparil S, Rocha-Singh K, Bhatt DL; SYMPLICITY HTN-3 Investigators. Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3. J Am Coll Cardiol. 2014 Sep 16;64(11):1071-8. doi: 10.1016/j.jacc.2014.05.012. Epub 2014 May 20.
citation: Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, Leon MB, Liu M, Mauri L, Negoita M, Cohen SA, Oparil S, Rocha-Singh K, Townsend RR, Bakris GL; SYMPLICITY HTN-3 Investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014 Apr 10;370(15):1393-401. doi: 10.1056/NEJMoa1402670. Epub 2014 Mar 29.