A Study of Renal Denervation in Patients With Treatment Resistant Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical and economic impact of implementation of renal denervation with the Symplicity™ Catheter System for treatment-resistant hypertension in Ontario, Canada.

Detailed Description
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This is a pragmatic randomized trial of renal nerve denervation for treatment resistant hypertension. This is part of a ministry sponsored MaRS-EXCITE program, to conduct early market health technology assessment, in order to determine appropriateness for provincial funding. We will assess the effectiveness, safety, economic attractiveness and feasibility of implementation of renal nerve denervation for treatment resistant hypertension. This will involve a new model of care which will include a multi-disciplinary team approach to these patients. Treatment resistant hypertension is defined as patients with uncontrolled hypertension despite being on optimal doses of 3 or more anti-hypertensive medications. Patients will be randomized to either standard treatment or renal nerve denervation and followed for 6 months to determine impact on blood pressure.

Official Title
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A Pragmatic Randomized Clinical Evaluation of Renal Denervation for Treatment Resistant Hypertension

Conditions
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Treatment-Resistant Hypertension

Intervention / Treatment
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* Device: Renal denervation device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ontario residents Aged 18 and over Diagnosis of treatment-resistant hypertension after assessment and optimization by a hypertension specialist following recommended evaluation and diagnosis as outlined by the American Heart Association Office systolic blood pressure ≥ 160 mmHg (≥ 150 mmHg for patients with type II diabetes mellitus) prior to optimization by a hypertension specialist Baseline average systolic 24 hour ambulatory blood pressure of ≥ 135 mmHg after optimization and prior to randomization Prescribed 3 or more antihypertensive medications of different classes, both prior to optimization and at randomization, one of which must be a diuretic (a medication can be counted more than once if it acts on different receptors) Suitable renal artery anatomy based on CT/MRI/renal angiography imaging: both renal arteries > 20 mm in length and > 4 mm in diameter without significant fibromuscular disease or renal artery stenosis (>50%) Exclusion Criteria: Secondary causes of hypertension: Primary aldosteronism (secondary to adrenal adenoma) Chronic kidney disease: creatinine clearance or eGFR < 45 ml/min/1.73m² (measured on 24 hour urine preferably or MDRD) Pheochromocytoma Cushing's syndrome Aortic coarctation (differential in brachial or femoral pulses, systolic bruit) Type 1 diabetes mellitus Pregnancy

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early renal denervation<br>Renal denervation takes place immediately after patient is randomized. | Device: Renal denervation device<br> <br> * Other names: Medtronic Symplicity™ Catheter Device;|
| Other: Delayed renal denervation<br>Renal denervation takes place 6 months after the patient is randomized. | Device: Renal denervation device<br> <br> * Other names: Medtronic Symplicity™ Catheter Device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average systolic 24-hour ambulatory blood pressure |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving target systolic blood pressure (on average 24-hour ambulatory blood pressure of <130 mmHg) on the same or fewer medications at the time of randomization |  | 6 months | 
| Average daytime and average night-time systolic ambulatory blood pressure |  | 6 months | 
| Variability of 24-hour ambulatory systolic blood pressure |  | 6 months | 
| Average office blood pressure using an approved, automated office blood pressure device |  | 6 months | 
| Hypertensive medication complexity index (MRCI) |  | 6 months | 
| Number of hypertensive medications |  | 6 months | 
| Peri-procedural mean cost per patient in Canadian dollars |  | 12 months | 
| Generic quality of life (EQ-5D) |  | 6 months | 
| Body Mass Index (BMI) |  | 6 months | 
| 24-hour urine sodium |  | 6 months | 
| Acute periprocedural renal injury |  | 72 hours post procedure | 
| Creatinine clearance measured on 24-hour urine (% change from baseline & indexed to Body Surface Area) |  | 6 months | 
| Vascular complications (dissection, pseudoaneurysm, AV fistula) |  | 6 months | 
| Evidence of renal artery stenosis compared to pre-procedure (determined by renal imaging, CT or MRA) for early intervention group |  | 6 months | 
| Composite cardiovascular endpoints (fatal & non-fatal MI, new onset heart failure, stroke, beginning dialysis, hospitalization for cardiovascular/renal reasons, increase in hypertension medications) |  | 6 months | 
| Microalbumin to creatinine ratio (MACR) from random urine sample (% change from baseline) |  | 6 months | 
| 24-hour urine sodium (% change from baseline) |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment-resistant hypertension, Renal denervation, Ambulatory blood pressure