A Study of Renal Denervation in Patients With Treatment Resistant Hypertension (PaCE)

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

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.

Study Overview

• Status: Terminated
• Conditions: Treatment-Resistant Hypertension
• Intervention / Treatment: Device: Renal denervation device

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Primary aldosteronism (secondary to adrenal adenoma)
  2. Chronic kidney disease: creatinine clearance or eGFR < 45 ml/min/1.73m² (measured on 24 hour urine preferably or MDRD)
  3. Pheochromocytoma
  4. Cushing's syndrome
  5. Aortic coarctation (differential in brachial or femoral pulses, systolic bruit)
• Type 1 diabetes mellitus
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Body Mass Index (BMI)	6 months
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
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

Collaborators and Investigators

• Sponsor: Dr. Harindra Wijeysundera
• Collaborators: Medtronic; Mars Excellence in Clinical Innovation and Technology Evaluation
• Investigators: Principal Investigator: Harindra C. Wijeysundera, MD, Sunnybrook Research Institute

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: July 3, 2013
• First Posted (Estimate): July 10, 2013

Study Record Updates

• Last Update Posted (Estimate): October 13, 2014
• Last Update Submitted That Met QC Criteria: October 10, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Renal denervation; Ambulatory blood pressure; Treatment-resistant hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: 322-2012