Clinical trial NCT03730519: UK Registry for Baroreflex Activation Therapy
Official title: Investigation of the Efficacy and Safety of Baroreflex Activation Therapy in Patients With Refractory Hypertension and Those With Highly Variable Blood Pressure Due to Peripheral Baroreflex Failure
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Baroreflex Failure Syndrome
Hypertension, Resistant to Conventional Therapy
Keywords: Refractory Hypertension
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
Collaborators: name: CVRx, Inc.
First posted: 2018-11-05
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a post-marketing open label twin arm, single centre clinical trial of electrical carotid sinus stimulation with the Barostim Neo device to target sub-optimally controlled arterial hypertension or highly variable blood pressure in patients for whom no alternative therapies are available.
Primary purpose: TREATMENT

Brief summary: This study is a post-marketing open label single arm, single centre clinical trial of electrical carotid sinus stimulation with the Barostim Neo device to target sub-optimally controlled arterial hypertension or highly variable blood pressure in patients for whom no alternative therapies are available.

Detailed description: Hypertension is a major health issue globally and is the number one risk factor for cardiovascular morbidity and mortality. Despite decades of innovation in pharmacotherapeutics, suboptimal BP control remains a problem worldwide. Alternative therapies for hypertension are therefore urgently needed.

This project addresses the following important unmet needs:

1. . Refractory hypertension may respond to device based approaches such as baroreflex activation therapy (BAT) but further independent research is needed to clarify the role of novel technologies. It is not possible to undertake research into BAT at all due to lack of funding and the manufacturer is not undertaking clinical trials of the therapy in the UK.
2. . Patients with highly variable BP disorders constitute a very small but important sub-group of the hypertensive population but are the most challenging to manage as no drug therapy exists to combat high and low BP simultaneously. This group of patients have very poor quality of life and are unable to work due to their profound BP variability. Many of them experience frequent hospital admissions for lengthy periods as a result of potentially life-threatening hypertension. Treatment with BAT may feasibly improve management of their condition by dampening BP variability and preventing hypertensive surges whilst allowing the patients to continue with measures to prevent hypotension using compression hosiery and drugs.

This project has the following objectives

Primary:

To establish a UK national registry for treatment of blood pressure disorders with baroreflex activation therapy in the following patient groups:

* Patients with refractory hypertension (Ref-HTN) regardless of pharmacotherapy (up to 15 patients)
* Patients with highly variable BP disorders (BPV) the aetiology of which indicates that peripheral baroreflex failure is the underlying diagnosis (up to 10 patients)

Secondary

* To undertake mechanistic research to better understand the mechanism of action of baroreflex activation therapy and the role of the baroreflex in hypertensive disorders by measuring indices of autonomic function (parasympathetic and sympathetic nervous system tone) and humoral factors such as renin/aldosterone and copeptin in response to BAT.
* To position the Barts BP Clinic as a national referral centre for the management of complex circulatory disorders with access to experimental treatments unavailable elsewhere in the UK.
* To foster a more 'joined up' approach to BAT by promoting awareness of its benefits among primary care practitioners and other secondary care specialists.

Eligibility criteria: Inclusion Criteria:

1. Patients will be enrolled following an informed consent. The subject will be able to understand and comply with protocol requirements, instructions and protocol restrictions.
2. The study subjects will be either:

   I. Refractory hypertensive patients (daytime systolic ambulatory BP (ABP) \> 150 mmHg) in whom all pharmacological approaches to control BP have failed or were intolerable.

   or II. Symptomatic patients with exaggerated BPV documented on daytime ABP monitoring (SD \>18 mmHg) who cannot achieve effective BP control with pharmacological approaches
3. For BPV group, evidence of peripheral baroreflex dysfunction as determined by non-invasive autonomic function testing
4. Patients will have been established on a stable antihypertensive treatment regime for at least 1 month by the time of participation in the study and changes in pharmacological intervention for the duration of the trial are to be avoided unless clinically mandated.

Exclusion Criteria:

* HTN secondary to an identifiable and treatable cause
* Carotid atherosclerosis determined by ultrasound or angiographic evaluation greater than 50% stenosis
* Ulcerative plaques in the carotid artery as determined by ultrasound or angiographic evaluation
* Bifurcation of the carotid on the side planned needs to be below level of mandible by ultrasound
* Uncontrolled, symptomatic cardiac bradyarrhythmias.
* Myocardial infarction, unstable angina or cerebral vascular accident within 3 months before implant.
* Clinically significant cardiac valvular disease
* Prior implant in the carotid sinus region,
* Currently implanted electrical medical devices,
* End stage renal (with eGFR \<15 mL/min) or liver disease
* Pregnancy or contemplating pregnancy.
* BMI \> 40 kg/sq m
* Inability to tolerate ambulatory blood pressure monitoring
* Patient with other co-morbidity likely to have life expectancy \<3y
* Systolic left heart failure with ejection fraction \<40%

Primary outcomes:
measure: Ambulatory Systolic & Diastolic Blood Pressure changes in patients with uncontrolled (refractory) hypertension
timeFrame: 6 months
measure: Ambulatory Systolic & Diastolic Blood Pressure variability change in patients with highly variable BP due to baroreflex failure
timeFrame: 6 months
measure: Incidence of Treatment-Emergent Adverse Events in both groups of patients
timeFrame: 6 months
Secondary outcomes:
measure: Change in European Quality of Life 5 dimension (Eq-5D) score in both groups of patients
timeFrame: 6 months
measure: Changes in autonomic indices in both groups of patients
timeFrame: 6 months
Other outcomes:
measure: Change in echocardiographic left ventricular mass in both groups of patients
timeFrame: 6 months
measure: Change in pulse wave velocity in both groups of patients
timeFrame: 6 months
measure: Change in antihypertensive whole medicine equivalent in both groups of patients
timeFrame: 6 months
Locations:
city: London
country: United Kingdom
facility: William Harvey Research Institute
Study officials:
affiliation: Queen Mary University of London
name: Melvin D Lobo, MBChB PhD
role: PRINCIPAL_INVESTIGATOR
References: