Trial Outcomes & Findings for Rheos® Pivotal Trial (NCT NCT00442286)

Last Updated: 2017-03-20

Results Overview

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%.

Recruitment status

COMPLETED

Study phase

Target enrollment

591 participants

Primary outcome timeframe

6 months post-activation

Results posted on

2017-03-20

Participant Flow

Of the 591 patients enrolled, 78 withdrew prior to implant and 187 screen-failed. 4 implants were unsuccessful, and 2 randomized patients were terminated prior to the randomization visit. 55 patients were roll-in patients that were not randomized. A total of 265 patients were both randomized and implanted.

Participant milestones

Participant milestones
Measure	Rheos® Device On 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Rheos® Device Off 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex
Overall Study STARTED	181	84
Overall Study 6 Months	177	83
Overall Study 12 Months	174	82
Overall Study COMPLETED	174	82
Overall Study NOT COMPLETED	7	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Rheos® Device On 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Rheos® Device Off 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex
Overall Study Death	2	2
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	2	0
Overall Study System explanted	1	0
Overall Study Patient Injury	1	0

Baseline Characteristics

Rheos® Pivotal Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Roll-In n=55 Participants Subjects that were not included in endpoint analyses	Rheos® Device On n=181 Participants 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Rheos® Device Off n=84 Participants 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Total n=320 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	46 Participants n=5 Participants	151 Participants n=7 Participants	75 Participants n=5 Participants	272 Participants n=4 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	30 Participants n=7 Participants	9 Participants n=5 Participants	48 Participants n=4 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	65 Participants n=7 Participants	38 Participants n=5 Participants	127 Participants n=4 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	116 Participants n=7 Participants	46 Participants n=5 Participants	193 Participants n=4 Participants
Race/Ethnicity, Customized African American	11 Participants n=5 Participants	30 Participants n=7 Participants	18 Participants n=5 Participants	59 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized White/Caucasian	40 Participants n=5 Participants	146 Participants n=7 Participants	59 Participants n=5 Participants	245 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment Netherlands	0 participants n=5 Participants	8 participants n=7 Participants	5 participants n=5 Participants	13 participants n=4 Participants
Region of Enrollment United States	55 participants n=5 Participants	165 participants n=7 Participants	74 participants n=5 Participants	294 participants n=4 Participants
Region of Enrollment Germany	0 participants n=5 Participants	8 participants n=7 Participants	5 participants n=5 Participants	13 participants n=4 Participants

PRIMARY outcome

Timeframe: 6 months post-activation

Outcome measures

Outcome measures
Measure	Rheos® Device On n=181 Participants 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Rheos® Device Off n=84 Participants 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex
Percent of Patients With a 10mmHg or Greater Reduction in Office Cuff Systolic Blood Pressure	54.1 percentage of participants Interval 46.9 to 61.4	46.4 percentage of participants Interval 35.8 to 57.1

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rheos® Device On n=97 Participants 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Rheos® Device Off 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex
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.	87.6 percentage of participants Interval 81.1 to Lower one-sided 97.5% confident bound interval was used	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rheos® Device On n=270 Participants 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Rheos® Device Off 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex
Serious Procedure- or System-related Adverse Event-free Rate in Both Implanted and Attempted Patients	74.8 percentage of participants Interval 70.5 to Lower one-sided 95% confidence bound interval was used	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rheos® Device On n=266 Participants 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Rheos® Device Off 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex
Major Hypertension-related and Serious Device-related Adverse Event-Free Rate in Both Implanted and Attempted Patients.	87.2 percentage of participants Interval 83.8 to Lower One-sided 95% confident bound interval was used.	—

PRIMARY outcome

Timeframe: 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%.

Outcome measures

Outcome measures
Measure	Rheos® Device On n=181 Participants 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Rheos® Device Off n=84 Participants 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex
Therapy-related Adverse Event-free Rate.	91.7 percentage of participants Interval 87.7 to 95.7	89.3 percentage of participants Interval 82.7 to 95.9

Adverse Events

Rheos® Device On

Serious events: 102 serious events

Other events: 75 other events

Deaths: 0 deaths

Rheos® Device Off

Serious events: 45 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Rheos® Device On n=181 participants at risk 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex	Rheos® Device Off n=84 participants at risk 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. Rheos® Baroreflex Hypertension System: Electrical activation of the Carotid Baroreflex
General disorders Chest Pain	6.1% 11/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	1.2% 1/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
General disorders Fatique	4.4% 8/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	7.1% 6/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
General disorders Local swelling	1.1% 2/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	6.0% 5/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
General disorders Pheripheral edema	2.2% 4/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	6.0% 5/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
Infections and infestations Nasopharyngitis	2.8% 5/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	6.0% 5/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
Injury, poisoning and procedural complications Inappropriate device stimulation of tissue	5.5% 10/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	4.8% 4/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
Metabolism and nutrition disorders Gout	1.1% 2/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	6.0% 5/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
Musculoskeletal and connective tissue disorders Neck Pain	6.1% 11/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	3.6% 3/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
Nervous system disorders Dizziness	3.3% 6/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	7.1% 6/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
Nervous system disorders Headache	13.3% 24/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	6.0% 5/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
Nervous system disorders Hypoaesthesia	9.4% 17/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	4.8% 4/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.
Vascular disorders Hypotension	10.5% 19/181 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.	10.7% 9/84 • 12 months post-randomization Due to the learning curve associated with the implant of the Rheos system, the initial subjects (up to a maximum of two) at each center that had not been previously implanted with the Rheos system will be non-randomized roll-in subjects. These subjects were not subjected to the formal efficacy and safety analysis process.

Additional Information

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