Evaluation of Safety Mechanisms of Renal Radioablation(RSRA)for Uncontrolled Hypertension

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Ottawa Hospital Research Institute
Sponsor:
Collaborator:
The Ottawa Hospital Academic Medical Association
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT01966952
First received: October 16, 2013
Last updated: October 17, 2013
Last verified: October 2013
  Purpose

Renal sympathetic radioablation disrupts the nerves by high radiofrequency signal which creates localized heat, eliminates the signal and decrease blood pressure.

The main purpose of this study is to evaluate blood pressure 12 months after radioablation, and to evaluate the short and long-term effects of the renal radioablation on the extent of changes in urine catecholamines level, vascular stiffness, and sympathetic nerve activity as linked with the changes in blood pressure. The study will also evaluate the effect radioablation has on the renal arteries as well as develop teaching sessions for family physicians and other specialists to educate them on this new treatment.


Condition
Uncontrolled Hypertension

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Centre of Excellence for Treatment of Resistant Hypertension: Establishment and Critical Evaluation of Efficacy, Mechanisms and Safety of Renal Sympathetic Radioablation.

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Blood pressure change post RSRA treatment [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Blood pressure(BP)will be assessed post Renal Radiosympathetic radioablation RSRA)by 24-hr Ambulatory blood pressure monitor (ABPM) using the daytime average of systolic BP


Secondary Outcome Measures:
  • efficacy [ Time Frame: 1-3-6-&12 months ] [ Designated as safety issue: Yes ]

    changes in daytime average systolic BP by 24-hr ABPM at 1,3, 6,& 12 months post RSRA

    - changes in urinary catecholamines, aldosterone, Pulse wave velocity(PWV), and Muscle Sympathetic Nerve activity (MSNA) at defined time points post treatment.


  • Safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Secondary safety outcomes will also include frequency of complications including development of renal artery stenosis post procedure, determined by CT angiogram.


Other Outcome Measures:
  • Education [ Time Frame: 24months ] [ Designated as safety issue: No ]
    Finally, formal evaluation of our teaching lectures on Diagnosis and Management of Resistant HTN will be part of outlined CMEs.


Estimated Enrollment: 18
Study Start Date: September 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Resistant Hypertension
Resistant hypertension as described as; patients with uncontrolled hypertension on 3 or more antihypertensive medications with no secondary causes for hypertension (i.e. hyperaldosteronism, renal artery stenosis)

Detailed Description:

The purpose of this study is to evaluate the efficacy, safety and selected mechanisms of renal sympathetic radioablation. The primary outcome of this study is change in BP 12 months post treatment as assessed from daytime average of systolic BP from 24-hr ABPM.

In this innovation program, we propose to evaluate the following aspects of renal sympathetic radioablation RSRA in Patients with Resistant HTN:

  1. Efficacy:

    Assessment of BP lowering effect in patients with true resistant HTN. In contrast to studies done so far, we will evaluate the true BP lowering effect of RSRA by performance of 24-hr ABPM prior to and at defined time points post procedure. We will screen out pseudohypertension using direct observed therapy. We will employ a rigorous protocol to include only patients with truly resistant HTN. Namely, we will screen for major forms of secondary HTN such as renal artery stenosis, pheochromocytoma, primary hyperaldosteronism, and Cushing's syndrome and exclude these patients from radioablation. We will also address the issue of white coat phenomena as a cause of false diagnosis of resistant HTN by 24-hr ABPM. This innovative approach will ensure a proper evaluation of the BP lowering potential of this method, as patients with secondary forms of HTN may not respond to RSRA. In contrast, those with white coat effect may show gradual improvement in BP control over time unrelated to RSRA.

  2. Safety: Imaging of the renal arteries. Our patients will undergo CT angiogram imaging of their renal arteries prior to procedure and at defined time points afterwards. In studies reported so far, imaging of the renal arteries was not standardized. In animals (swines) subjected to RSRA using the same catheter, renal arteries showed fibrosis of 10-25% of the total media and underlying adventitia, with mild disruption of the external elastic lamina. Furthermore, a case report has been published documenting renal artery stenosis within 3 months post RSRA.
  3. Education on diagnosis and treatment of resistant HTN. As resistant HTN is frequently misdiagnosed and consequently poorly treated, we will develop teaching sessions for family physicians, general internists, and subspecialists from this LHIN region to make them aware of issues related to diagnosis of true resistant HTN and to educate them on this new option of treatment.
  4. Mechanism:

Effects of RSRA on Central Sympathetic Outflow, PWV, and aldosterone will be assessed pre and post RSRA and correlated to (changes in) BP prior to and at defined time points post RSRA.

Clinical relevance:

This is a new method for treatment of patients with resistant HTN. As our team has successfully treated two patients with resistant HTN in June 2012 (as the second team and centre in Canada), TOH/UOHI with experts in Clinical HTN, Nephrology, Interventional Cardiology and Interventional Radiology are uniquely positioned to establish and critically evaluate the suitability of this method for patients from our LHIN region. Pilot data on Pulse Wave Velocity, MSNA and aldosterone by RSRA will shed light on mechanisms involved in BP lowering by RSRA and will be used for the development of grant applications to Canadian peer review funding agencies.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

All patients will be recruited from the Hypetension Units at The Ottawa Hospital and the University of Ottawa Heart Institute. Only patients with uncontrolled hypertension will be eligable.

Criteria

Inclusion Criteria:

  • Adult patients (>18 years)
  • resistant HTN defined as daytime BP readings above 140/90 mmHg (as assessed from 24-hr ABPM))
  • on 4 or more BP lowering drugs

Exclusion Criteria:

  • pregnant patients
  • Secondary forms of hypertension
  • patients with following conditions: eGFR <45 ml/min/1.75 m2,
  • active infection,
  • known coagulopathies,
  • acute coronary syndrome and/or within 6 months post acute coronary event,
  • clinically significant arrhythmias,
  • within 6 months post stroke/TIA, severe liver disease;
  • psychiatric disorders and/or otherwise unable to sign consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01966952

Contacts
Contact: Marcel Ruzicka, MD 613-738-8400 ext 82535 mruzicka@toh.on.ca
Contact: Judy A Cheesman, RN 613-738-8400 ext 82514 jcheesman@ohri.ca

Locations
Canada, Ontario
The Hypetension Unit of The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 7W9
Contact: Marcel Ruzicka, MD    613-738-8400 ext 82535    mruzicka@toh.on.ca   
Contact: Judy A Cheesman, RN    613-738-8400 ext 82514    jcheesman@ohri.ca   
Principal Investigator: Marcel Ruzicka, MD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
The Ottawa Hospital Academic Medical Association
Investigators
Principal Investigator: Marcel Ruzicka, MD The Ottawa Hospital Research Institute
  More Information

No publications provided

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT01966952     History of Changes
Other Study ID Numbers: 20130444-01H
Study First Received: October 16, 2013
Last Updated: October 17, 2013
Health Authority: Canada:Ottawa Health Science Network Research Ethics Board
Canada:Ottawa Hospital Research Institute

Keywords provided by Ottawa Hospital Research Institute:
Hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 28, 2014