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UK Registry for Baroreflex Activation Therapy

Not Applicable
Terminated
Conditions
Baroreflex Failure Syndrome
Hypertension, Resistant to Conventional Therapy
Interventions
Device: Baroreflex Activation Therapy with Barostim Neo
Registration Number
NCT03730519
Lead Sponsor
Queen Mary University of London
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
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%

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Patients with refractory hypertensionBaroreflex Activation Therapy with Barostim NeoPatients with refractory hypertension which cannot be controlled with drug therapy in the hands of hypertension specialists will be treated with Baroreflex Activation Therapy with Barostim Neo and followed up for a period of up to 3 years
Patients with highly variable BPBaroreflex Activation Therapy with Barostim NeoPatients with symptomatic highly variable blood pressure due to afferent baroreceptor failure which cannot be controlled with drug therapy in the hands of hypertension specialists will be treated with Baroreflex Activation Therapy with Barostim Neo and followed up for a period of up to 3 years
Primary Outcome Measures
NameTimeMethod
Incidence of Treatment-Emergent Adverse Events in both groups of patients6 months
Ambulatory Systolic & Diastolic Blood Pressure variability change in patients with highly variable BP due to baroreflex failure6 months
Ambulatory Systolic & Diastolic Blood Pressure changes in patients with uncontrolled (refractory) hypertension6 months
Secondary Outcome Measures
NameTimeMethod
Change in European Quality of Life 5 dimension (Eq-5D) score in both groups of patients6 months

Eq5D is a standardised/validated instrument to assess health outcome. It consists of five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, and a self-rated health scale on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. An Eq5D index of 1.0 indicates full health, and -0.59 denoted death

Changes in autonomic indices in both groups of patients6 months

Non-invasive measurement of parasympathetic (vagal) tone and sympathetic tone using a Neuroscope measurement device with real time beat to beat BP measurement

Trial Locations

Locations (1)

William Harvey Research Institute

🇬🇧

London, United Kingdom

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