Effect of Renal Sympathetic Denervation on Resistant Hypertension and Cardiovascular Hemodynamic in Comparison to Intensive Medical Therapy Utilizing Impedance Cardiography

NCT01673516 | Unknown Phase 2 DMC

• 1 other identifier: 2012/145/REK
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to demonstrate that Renal Sympathetic Denervation (RDN) improves the control of blood pressure (BP) in patients with treatment-resistant hypertension, as compared to intensive medical therapy (IMT) using hemodynamic parameters and then applying a predefined algorithm of drug selection (i.e. integrated hemodynamic management - IHM) during 6 months intensive treatment program (receiving antihypertensive care according to the 2007 ESH Guidelines). Working hypothesis: When it is possible to disrupt the sympatho-renal axis by RDN - BP reduction occurs to a greater extent and more rapidly than applying intensive medical therapy using IHM.

Conditions

Hypertension, Resistant to Conventional Therapy

Keywords

Renal sympathetic denervation; Impedance cardiography

Outcome Measures

Primary Outcomes (1)

• Absolute change in office systolic blood pressure(SBP)

  is the absolute change in office SBP, after a 6 months follow-up.

  at 6 months

Secondary Outcomes (4)

• Short and long term safety of RDN as an interventional procedure

  up to10 years

• Percentage of normalization of blood pressure(BP) at office, home and ABPM

  at 6 months and later

• The normalization of hemodynamics.

  at 6 month and later

• Cost effectiveness

  At 6 month and later

Other Outcomes (1)

• The quality of life and side effects related to antihypertensive agents

  at 6 months and later

Study Arms (2)

group Co

ACTIVE COMPARATOR

group Co receives intensive medical therapy utilizing integrated hemodynamic management calculated by impedance cardiography of "The HOTMAN® System"

Device: The HOTMAN® System

group RDN

ACTIVE COMPARATOR

For patients who will be randomly assigned to undergo renal denervation by "The SymplicityTM Renal Denervation System", the femoral artery will be accessed with the standard endovascular technique and the catheter will be advanced into the renal artery and connected to a radiofrequency generator. As in Symplicity HTN 1 and 2 trials, four-to-six discrete, low-power radiofrequency ablations lasting up to 2 min each and of 8 watts or less to obtain up to four-six ablations separated both longitudinally and rotationally within each renal artery. During ablation, the catheter system monitored tip temperature and impedance, altering radiofrequency energy delivery in response to a predetermined algorithm.

Procedure: The SymplicityTM Renal Denervation System

Interventions

The SymplicityTM Renal Denervation System PROCEDURE

For patients who will be randomly assigned to undergo renal denervation (group RDN), the femoral artery will be accessed with the standard endovascular technique and the catheter will be advanced into the renal artery and connected to a radiofrequency generator. As in Simplicity HTN 1 and 2 trials, four-to-six discrete, low-power radiofrequency ablations lasting up to 2 min each and of 8 watts or less to obtain up to four-six ablations separated both longitudinally and rotationally within each renal artery. During ablation, the catheter system monitored tip temperature and impedance, altering radiofrequency energy delivery in response to a predetermined algorithm.

group RDN

The HOTMAN® System DEVICE

Impedance Cardiography by HOTMAN system will evaluates non-invasively hemodynamic parameters in patients randomized to "group Co"

group Co

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Average SBP \>140mmHg, measured per guidelines
• hour average ABPM daytime SBP \>135mm/Hg
• On stable medication regimen of full tolerated doses of 3 or more antihypertensive meds, with one being a diuretic
• No changes for a minimum of 2 weeks prior to screening
• No planned medication changes for 6 months
• Age 18-80 years
• At minimum, 3 antihypertensive medications must meet one or more of the following full dose criteria:
• Highest labeled dose according to medication's labeling
• Highest usual dose per clinical guidelines-JNC-7
• Highest tolerated dose
• Highest appropriate dose for the patient per the PI's clinical judgment

You may not qualify if:

• Hemodynamically or anatomically significant renal artery abnormalities or stenosis \>50% or prior renal artery intervention
• eGFR \< 45 mL/min/1.73m2 (MDRD formula)
• Albumin/creatinine ratio \> 50 mg/mmol
• Type 1 diabetes mellitus
• Known alcohol or drug abuse
• Symptomatic orthostatic hypotension in past year
• Stenotic valvular heart disease for which BP reduction would be hazardous
• MI, unstable angina, or CVA in the prior 6 months
• Known primary pulmonary HTN
• Known pheochromocytoma, Cushing's disease, coarctation of the aorta, hyperthyroidism or hyperparathyroidism
• Known primary hyperaldosteronism not adequately treated.

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, Oslo County, 0424, Norway

Location

Related Publications (5)

• Halvorsen LV, Bergland OU, Soraas CL, Larstorp ACK, Hjornholm U, Kjaer VN, Kringen MK, Clasen PE, Haldsrud R, Kjeldsen SE, Rostrup M, Fadl Elmula FEM, Opdal MS, Hoieggen A. Nonadherence by Serum Drug Analyses in Resistant Hypertension: 7-Year Follow-Up of Patients Considered Adherent by Directly Observed Therapy. J Am Heart Assoc. 2022 Sep 20;11(18):e025879. doi: 10.1161/JAHA.121.025879. Epub 2022 Sep 8.

  PMID: 36073648 DERIVED

• Undrum Bergland O, Larstorp ACK, Lund Soraas C, Hoieggen A, Rostrup M, Norheim Kjaer V, Godang K, Sevre K, Fadl Elmula FEM. Changes in sympathetic nervous system activity after renal denervation: results from the randomised Oslo RDN study. Blood Press. 2021 Jun;30(3):154-164. doi: 10.1080/08037051.2020.1868286. Epub 2021 Jan 5.

  PMID: 33399016 DERIVED

• Fadl Elmula FE, Hoffmann P, Larstorp AC, Fossum E, Brekke M, Kjeldsen SE, Gjonnaess E, Hjornholm U, Kjaer VN, Rostrup M, Os I, Stenehjem A, Hoieggen A. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension. 2014 May;63(5):991-9. doi: 10.1161/HYPERTENSIONAHA.114.03246. Epub 2014 Mar 3.

  PMID: 24591332 DERIVED

• Kjeldsen SE, Narkiewicz K, Oparil S, Hedner T. Blood pressure lowering effect of renal sympathetic denervation or placebo? - building expectations for Symplicity-HTN 3. Blood Press. 2013 Oct;22(5):279-81. doi: 10.3109/08037051.2013.840445. No abstract available.

  PMID: 24059787 DERIVED

• Fadl Elmula FE, Hoffmann P, Fossum E, Brekke M, Gjonnaess E, Hjornholm U, Kjaer VN, Rostrup M, Kjeldsen SE, Os I, Stenehjem AE, Hoieggen A. Renal sympathetic denervation in patients with treatment-resistant hypertension after witnessed intake of medication before qualifying ambulatory blood pressure. Hypertension. 2013 Sep;62(3):526-32. doi: 10.1161/HYPERTENSIONAHA.113.01452. Epub 2013 Jul 8.

  PMID: 23836798 DERIVED

MeSH Terms

Conditions

Hypertension Resistant to Conventional Therapy

Study Officials

• Aud Høieggen, MD, PhD

  Oslo University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2012
• First Posted: August 28, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: August 1, 2022
• Last Updated: October 30, 2015

Record last verified: 2015-10

Locations

NO (1)