Rheos® Pivotal Trial

Not Applicable

Completed

Conditions: Hypertension

Interventions: Device: Rheos® Baroreflex Hypertension System

Registration Number: NCT00442286

Lead Sponsor: CVRx, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 591

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Off	Rheos® Baroreflex Hypertension System	Subject will be randomized to a 2:1 allocation to the Rheos ON or OFF arms at the time of Rheos System activation (time point 0). After the six month follow up evaluation, all subjects will have therapy activated, though subjects and treating physicians will not be informed of randomized treatment assignment.
On	Rheos® Baroreflex Hypertension System	Subject will be randomized to a 2:1 allocation to the Rheos ON or OFF arms at the time of Rheos System activation (time point 0). After the six month follow up evaluation, all subjects will have therapy activated, though subjects and treating physicians will not be informed of randomized treatment assignment.

Primary Outcome Measures

Name	Time	Method
Percent of Patients With a 10mmHg or Greater Reduction in Office Cuff Systolic Blood Pressure	6 months post-activation	Compare Group A (Rheos® Device On ) versus Group B (Rheos® Device Off) via a double-blind, randomized, parallel group, super-superiority design for proportion of subjects that achieve at least a 10 mm Hg drop in systolic blood pressure at Month 6 compared to Month 0, with a superiority margin of 20%.
Major Hypertension-related and Serious Device-related Adverse Event-Free Rate in Both Implanted and Attempted Patients.	12 months-post activation	Compare the event-free rate for all major hypertension-related and serious device-related adverse events occurring between 30 days post-implant and the Month 12 visit, to a pre-specified objective performance criterion of 72% based on similar implantable devices such as defibrillators and resynchronization devices. Note: The purpose of this outcome measure was to evaluate the effect of having the device implanted, not to compare the outcomes between the two treatment groups. Therefore, both groups were analyzed as a single cohort.
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.	12 months post-activation	Compare the sustained response in SBP Month 12 in Group A ( Rheos® Device On ) responders at Month 6 to an objective performance criterion of 65%. A sustained response to therapy required the reduction from Month 0 to Month 12 to be at least 10 mmHg and to remain at least 50% of that seen at Month 6.
Serious Procedure- or System-related Adverse Event-free Rate in Both Implanted and Attempted Patients	30 days post implant	Compare the serious procedure- or system-related adverse event-free rate for events occurring within 30 days of implant to a pre-specified objective performance criterion of 82% set based on historical literature on implantable cardioverter defibrillators (ICD) and pacemakers. Note: The purpose of this outcome measure was to evaluate the effect of having the device implanted, not to compare the outcomes between the two treatment groups. Therefore, both groups were analyzed as a single cohort.
Therapy-related Adverse Event-free Rate.	6 months post-activation	Compare Group A (Rheos® Device On ) versus Group B (Rheos® Device Off) therapy-related adverse event-free rates via a double-blind, randomized, parallel group, non-inferiority design for therapy-related serious adverse events occurring between 30 days post-implant and the Month 6 visit. The non-inferiority margin was 15%.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (44): University of Southern California
🇺🇸
Los Angeles, California, United States
University of Chicago, Dept. of Medicine, Section of Endocinology, Diabetes & Metabolism
🇺🇸
Chicago, Illinois, United States
The Lindner Clinical Trial Center
🇺🇸
Cincinnati, Ohio, United States
The Methodist Hospital Research Institute
🇺🇸
Houston, Texas, United States
Apex Cardiology
🇺🇸
Inglewood, California, United States
St Joseph Health
🇺🇸
Orange, California, United States
George Washington University Hospital
🇺🇸
Washington, District of Columbia, United States
Jacksonville Center for Clinical Research
🇺🇸
Jacksonville, Florida, United States
The Heart and Vascular Institute of Florida
🇺🇸
St. Petersburg, Florida, United States
The Care Group
🇺🇸
Indianapolis, Indiana, United States
Pensacola Research Consultants
🇺🇸
Pensacola, Florida, United States
Iowa Heart Center
🇺🇸
West Des Moines, Iowa, United States
Southeast Regional Research Group
🇺🇸
Columbus, Georgia, United States
The Center for Cardiovascular Studies, LLC
🇺🇸
Shawnee Mission, Kansas, United States
Brigham & Womens Hospital
🇺🇸
Boston, Massachusetts, United States
Washington University
🇺🇸
St.Louis, Missouri, United States
Nebraska Heart Institute
🇺🇸
Lincoln, Nebraska, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Rex HealthCare
🇺🇸
Raleigh, North Carolina, United States
Ohio State Medical Center
🇺🇸
Columbus, Ohio, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
Jobst Vascular Center
🇺🇸
Toledo, Ohio, United States
Allegheny General Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
Temple University Health System
🇺🇸
Philadelphia, Pennsylvania, United States
Sanford Clinical Research
🇺🇸
Sioux Falls, South Dakota, United States
Clinical Research Solutions, P.C.
🇺🇸
Knoxville, Tennessee, United States
Scott and White Memoral Hospital
🇺🇸
Temple, Texas, United States
Medizinische Hochschule Hannover
🇩🇪
Hannover, Germany
University Hospital Maastricht
🇳🇱
Maastricht, Netherlands
Swedish Medical Center
🇺🇸
Seattle, Washington, United States
Lancaster General Hospital
🇺🇸
Lancaster, Pennsylvania, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
VA Medical Center
🇺🇸
Washington, District of Columbia, United States
Saint Thomas Research Institute
🇺🇸
Nashville, Tennessee, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
Oklahoma Foundation for Cardiovascular Research
🇺🇸
Oklahoma City, Oklahoma, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Florida Hospital Cardiovascular Institute
🇺🇸
Orlando, Florida, United States
Florida Cardiovascular Institute
🇺🇸
Tampa, Florida, United States
Forsyth Medical Center
🇺🇸
Winston-Salem, North Carolina, United States
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States