Clinical trial NCT00442286: Rheos® Pivotal Trial
Official title: Rheos® Pivotal Trial: Rheos™ Baroreflex Hypertension Therapy System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Keywords: Hypertension
High Blood Pressure
Blood Pressure
Cardiovascular Disease
Resistant Hypertension
Stage 2 Hypertension
Hypertension that is resistant to treatment
Lead sponsor: CVRx, Inc.
Sponsor class: INDUSTRY
First posted: 2007-03-01
Enrollment: 591
Sex: ALL
Minimum age (years): 21
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 clinical trial is to demonstrate the efficacy and safety of the Rheos system in subjects with hypertension that are resistant to treatment with at least three anti-hypertension agents, one of which is a diuretic.


Eligibility criteria: Inclusion Criteria:

* Be at least 21 years of age and no more than 80 years of age.
* Have been assessed with bilateral carotid bifurcations that are easily interrogated by carotid duplex ultrasound and are below the level of the mandible.
* Office cuff systolic blood pressure greater than or equal to 160 mmHg and have a diastolic blood pressure greater than or equal to 80 mmHg as well as a 24-hour ambulatory systolic blood pressure greater than or equal to 135 mmHg despite at lest one month of maximally tolerated therapy with at least three anti-hypertensive medications, of which at least one must be a diuretic.
* Must have completed the drug compliance questionnaire and have been judged to be compliant with medications.
* For subjects that have had prior bariatric surgery, they must be at least 1 year post-surgery and at a stable weight.
* If female, the subject must be surgically sterile, or using a medically accepted method of birth control and agree to continue use of this method for the duration of the trial. Women of childbearing potential must have a negative serum pregnancy test in the pre-implant blood evaluation.
* Must be an appropriate or reasonable surgical candidate.
* Have signed a CVRx approved informed consent form for participation in this study

Exclusion Criteria:

* Have known or suspected baroreflex failure or autonomic neuropathy.
* Have an arm circumference greater than 46 cm and/or body mass index of greater than 45.
* Have significant cardiac bradyarrhythmias.
* Have chronic atrial fibrillation.
* Have significant orthostatic hypotension
* Had a solid organ or hematologic transplant.
* Had a myocardial infarction, unstable angina, syncope, or cerebral vascular accident within the past 3 months.
* Have carotid atherosclerosis producing a 50% or greater reduction in linear diameter as determined by ultrasound or angiographic evaluation as determined within 6 months of enrollment in the trial.
* Have ulcerative plaques in the carotid artery as determined by ultrasound or angiographic evaluation.
* Have prior surgery, radiation, or endovascular stent placement in either carotid sinus region.
* Have severe chronic kidney disease as defined by:

  * Currently undergoing dialysis or dialysis is planned within 3 months of the implant date
  * eGFR of ≤30 ml/min/1.73m²
* Have hypertension secondary to an identifiable and treatable cause other than sleep apnea.
* Have clinically significant cardiac structural valvular disease.
* Have clinically significant reactive airway disease, chronic obstructive pulmonary disease, and/or primary pulmonary hypertension.
* Have an uncontrolled comorbid medical condition that would adversely affect participation in the trial.
* Have a clinically significant psychological illness that would prohibit the subject's ability to meet the protocol requirements
* Are currently taking an imidazolone receptor agonist
* Are unable or unwilling to fulfill the protocol medication compliance and follow-up requirements.
* Have an active infection within the last month.
* Have a co-morbid condition that reduces life expectancy to less than one year.
* Are enrolled in another concurrent clinical trial, without prior approval of CVRx.

Primary outcomes:
measure: Percent of Patients With a 10mmHg or Greater Reduction in Office Cuff Systolic Blood Pressure
timeFrame: 6 months post-activation
measure: Percent of Group A (Rheos® Device On) Patients Who Maintain a 10 mm Hg Drop in Systolic Blood Pressure at 12 Months Post-activation, and Whose Response at 12 Months is at Least 50% of the Response Observed at 6 Months Post-activation.
timeFrame: 12 months post-activation
measure: Serious Procedure- or System-related Adverse Event-free Rate in Both Implanted and Attempted Patients
timeFrame: 30 days post implant
measure: Major Hypertension-related and Serious Device-related Adverse Event-Free Rate in Both Implanted and Attempted Patients.
timeFrame: 12 months-post activation
measure: Therapy-related Adverse Event-free Rate.
timeFrame: 6 months post-activation
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Inglewood
country: United States
facility: Apex Cardiology
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Orange
country: United States
facility: St Joseph Health
state: California
city: Washington
country: United States
facility: George Washington University Hospital
state: District of Columbia
city: Washington
country: United States
facility: VA Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cardiovascular Institute
state: Florida
city: Pensacola
country: United States
facility: Pensacola Research Consultants
state: Florida
city: St. Petersburg
country: United States
facility: The Heart and Vascular Institute of Florida
state: Florida
city: Tampa
country: United States
facility: Florida Cardiovascular Institute
state: Florida
city: Columbus
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Chicago
country: United States
facility: University of Chicago, Dept. of Medicine, Section of Endocinology, Diabetes & Metabolism
state: Illinois
city: Indianapolis
country: United States
facility: The Care Group
state: Indiana
city: West Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Shawnee Mission
country: United States
facility: The Center for Cardiovascular Studies, LLC
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Brigham & Womens Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: St.Louis
country: United States
facility: Washington University
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Raleigh
country: United States
facility: Rex HealthCare
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State Medical Center
state: Ohio
city: Toledo
country: United States
facility: Jobst Vascular Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Cardiovascular Research
state: Oklahoma
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Health System
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Clinical Research
state: South Dakota
city: Knoxville
country: United States
facility: Clinical Research Solutions, P.C.
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas Research Institute
state: Tennessee
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Temple
country: United States
facility: Scott and White Memoral Hospital
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Maastricht
country: Netherlands
facility: University Hospital Maastricht
Study officials:
affiliation: Washington University School of Medicine
name: Luis Sanchez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Mitra Nadim, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wachter R, Halbach M, Bakris GL, Bisognano JD, Haller H, Beige J, Kroon AA, Nadim MK, Lovett EG, Schafer JE, de Leeuw PW. An exploratory propensity score matched comparison of second-generation and first-generation baroreflex activation therapy systems. J Am Soc Hypertens. 2017 Feb;11(2):81-91. doi: 10.1016/j.jash.2016.12.003. Epub 2016 Dec 16.
citation: de Leeuw PW, Alnima T, Lovett E, Sica D, Bisognano J, Haller H, Kroon AA. Bilateral or unilateral stimulation for baroreflex activation therapy. Hypertension. 2015 Jan;65(1):187-92. doi: 10.1161/HYPERTENSIONAHA.114.04492. Epub 2014 Oct 20.