Rheos® Pivotal Trial

Study Overview
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Brief Summary
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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.

Official Title
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Rheos® Pivotal Trial: Rheos™ Baroreflex Hypertension Therapy System

Conditions
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Hypertension

Intervention / Treatment
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* Device: Rheos® Baroreflex Hypertension System


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: On<br>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. | Device: Rheos® Baroreflex Hypertension System<br>* Electrical activation of the Carotid Baroreflex<br>|
| Experimental: Off<br>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. | Device: Rheos® Baroreflex Hypertension System<br>* Electrical activation of the Carotid Baroreflex<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients With a 10mmHg or Greater Reduction in Office Cuff Systolic Blood Pressure | 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%. | 6 months post-activation | 
| 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. | 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. | 12 months post-activation | 
| Serious Procedure- or System-related Adverse Event-free Rate in Both Implanted and Attempted Patients | 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. | 30 days post implant | 
| Major Hypertension-related and Serious Device-related Adverse Event-Free Rate in Both Implanted and Attempted Patients. | 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. | 12 months-post activation | 
| Therapy-related Adverse Event-free Rate. | 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%. | 6 months post-activation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, High Blood Pressure, Blood Pressure, Cardiovascular Disease, Resistant Hypertension, Stage 2 Hypertension, Hypertension that is resistant to treatment