HypertensionNCT00442286
Rheos® Pivotal Trial
A study testing Rheos® Baroreflex Hypertension System in people with Hypertension, run by CVRx, Inc. at 44 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Rheos® Baroreflex Hypertension System
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 591 participants
- Where
- 44 sitesin 3 countries
- Study dates
- Oct 2006to Jan 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 23Show fewer
- 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.
Trial locations and contacts
44 sites in 3 countries.
44 sites in 3 countries
United States42 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Brigham & Womens Hospital
Boston, Massachusetts, 02115
University of Chicago, Dept. of Medicine, Section of Endocinology, Diabetes & Metabolism
Chicago, Illinois, 60637
The Lindner Clinical Trial Center
Cincinnati, Ohio, 45219
University Hospitals Case Medical Center
Cleveland, Ohio, 44106
Southeast Regional Research Group
Columbus, Georgia, 31904
Ohio State Medical Center
Columbus, Ohio, 43210
Henry Ford Health System
Detroit, Michigan, 48202
Hackensack University Medical Center
Hackensack, New Jersey, 07601
The Methodist Hospital Research Institute
Houston, Texas, 77030
The Care Group
Indianapolis, Indiana, 46290
Apex Cardiology
Inglewood, California, 90301
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216
Clinical Research Solutions, P.C.
Knoxville, Tennessee, 37920
Lancaster General Hospital
Lancaster, Pennsylvania, 17604
University of Kentucky
Lexington, Kentucky, 40536
Nebraska Heart Institute
Lincoln, Nebraska, 68526
University of Southern California
Los Angeles, California, 90033
University of Minnesota
Minneapolis, Minnesota, 55455
Saint Thomas Research Institute
Nashville, Tennessee, 37205
Columbia University Medical Center
New York, New York, 10032
Oklahoma Foundation for Cardiovascular Research
Oklahoma City, Oklahoma, 73120
St Joseph Health
Orange, California, 92868
Florida Hospital Cardiovascular Institute
Orlando, Florida, 32803
Pensacola Research Consultants
Pensacola, Florida, 32504
Temple University Health System
Philadelphia, Pennsylvania, 19140
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Rex HealthCare
Raleigh, North Carolina, 27607
Virginia Commonwealth University
Richmond, Virginia, 23298
University of Rochester
Rochester, New York, 14623
Swedish Medical Center
Seattle, Washington, 98122
The Center for Cardiovascular Studies, LLC
Shawnee Mission, Kansas, 66204
Sanford Clinical Research
Sioux Falls, South Dakota, 57104
Washington University
St Louis, Missouri, 63110
The Heart and Vascular Institute of Florida
St. Petersburg, Florida, 33709
Florida Cardiovascular Institute
Tampa, Florida, 33609
Scott and White Memoral Hospital
Temple, Texas, 76508
Jobst Vascular Center
Toledo, Ohio, 43606
George Washington University Hospital
Washington D.C., District of Columbia, 20037
VA Medical Center
Washington D.C., District of Columbia, 20422
Iowa Heart Center
West Des Moines, Iowa, 50266
Forsyth Medical Center
Winston-Salem, North Carolina, 27103
About this study
Official title: Rheos® Pivotal Trial: Rheos™ Baroreflex Hypertension Therapy System
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.
- Conditions
- Hypertension
- Being tested
- Rheos® Baroreflex Hypertension System
- Keywords
- Hypertension, High Blood Pressure, Blood Pressure, Cardiovascular Disease, Resistant Hypertension, Stage 2 Hypertension, Hypertension that is resistant to treatment
- Medical subject headings
- Hypertension, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rheos® Baroreflex Hypertension SystemDevice
Electrical activation of the Carotid Baroreflex
| Study group | Role | What they receive |
|---|---|---|
| On | Experimental | 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. Receives: Device: Rheos® Baroreflex Hypertension System |
| Off | Experimental | 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. Receives: Device: Rheos® Baroreflex Hypertension System |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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%.
Measured: 6 months post-activation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2007 (estimated)
- Study startOct 2006
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 591 participants (actual)
Sponsor and investigators
- Lead sponsor
- CVRx, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Luis Sanchez, MD, Principal investigator, Washington University School of MedicineMitra Nadim, MD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00442286
- Sponsor's protocol ID
- 360009
- Status last verified
- Jan 2017
- First submitted
- 27 Feb 2007
- Last updated
- 20 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 28065708de 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.
PubMed 25331845
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rheos® Pivotal Trial: Rheos™ Baroreflex Hypertension Therapy System
- ClinicalTrials.gov ID
- NCT00442286
- Acronym / sponsor ID
- 360009
- Conditions
- Hypertension
- Keywords
- Hypertension, High Blood Pressure, Blood Pressure, Cardiovascular Disease, Resistant Hypertension, Stage 2 Hypertension, Hypertension that is resistant to treatment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 591 participants (actual)
- Lead sponsor
- CVRx, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2006
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 1 Mar 2007 (estimated)
- Results
- Posted 20 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| On | Experimental | Device: Rheos® Baroreflex Hypertension SystemSubject 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. |
| Off | Experimental | Device: Rheos® Baroreflex Hypertension SystemSubject 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. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rheos® Baroreflex Hypertension SystemElectrical activation of the Carotid Baroreflex | Device | Off, On |
Primary outcome
Percent of Patients With a 10mmHg or Greater Reduction in Office Cuff Systolic Blood Pressure
Time frame: 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%.
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.
Time frame: 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
Time frame: 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.
Major Hypertension-related and Serious Device-related Adverse Event-Free Rate in Both Implanted and Attempted Patients.
Time frame: 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.
Therapy-related Adverse Event-free Rate.
Time frame: 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%.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28065708Wachter 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.
- Derived from this study: PubMed 25331845de 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.
- Additional information about the Rheos Pivotal Trial for patients and medical professionals can be found at http://www.bloodpressuretrial.com/Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis Sanchez, MD principal investigator
Washington University School of Medicine
Mitra Nadim, MD principal investigator
University of Southern California
44 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rheos® Baroreflex Hypertension System in people with Hypertension, run by CVRx, Inc. at 44 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Patients With a 10mmHg or Greater Reduction in Office Cuff Systolic Blood Pressure (time frame: 6 months post-activation). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00442286, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2017.