Renal Sympathectomy in Treatment Resistant Essential Hypertension, a Sham Controlled Randomized Trial (ReSET)

The purpose of this double blind, randomized and sham controlled study is to determine whether renal denervation in terms of catheter based ablation in the renal arteries is effective in lowering blood pressure in patients with treatment resistant hypertension. The blood pressure lowering effect will be evaluated by 24 hours ambulatory blood pressure measurement at baseline and after 1, 3 and 6 months of follow up. Secondary end point evaluation concerns hemodynamic measures using echocardiography, applanation tonometry and forearm plethysmography.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Procedure: Renal artery ablation; Procedure: Renal angiography

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N
    • Aarhus, Aarhus N, Denmark, 8200
      • Skejby Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Systolic daytime ambulatory BP at least 145 mmHg and compliance to a minimum of 3 antihypertensive drugs, including a diuretic, or in case of diuretic intolerance at least 3 nondiuretic antihypertensive drugs.

Exclusion Criteria:

• Pregnancy
• Non compliance
• Heart Failure (NYHA 3-4)
• LV ejection fraction < 50 %
• Renal insufficiency (eGFR<30)
• Unstable coronary heart disease
• Coronary intervention within 6 months
• Myocardial infarction within 6 months
• Claudication
• Orthostatic syncope within 6 months
• Secondary Hypertension
• Permanent atrial fibrillation
• Significant Heart Valve Disease
• Clinically Significant abnormal electrolytes, haemoglobin, Liver enzymes, TSH
• Second and third degree heart block
• Macroscopic haematuria
• Proximal significant coronary stenosis
• Renal artery anatomy not suitable for renal artery ablation (Stenosis, small diameter < 4 mm, length < 2 cm, multiple renal arteries, severe calcifications)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Renal artery ablation; By femoral access, coronary and renal angiography are performed. The patient will be sedated. In case of vessel anatomy allowing renal ablation, the patient will be randomized in the card. lab. In case of randomization to active treatment, renal artery ablation will be carried out straight away.	Procedure: Renal artery ablation; Catheter based renal denervation by applying low power radiofrequency to the renal artery using the Ardian Medtronic Simplicity Catheter, introduced by femoral artery access.
SHAM_COMPARATOR: Sham; By femoral access, coronary and renal angiography are performed. The patient will be sedated. In case of vessel anatomy allowing renal ablation, the patient will be randomized in the card. lab. In case of randomization to sham procedure, no renal artery ablation are performed.	Procedure: Renal angiography; Renal angiography by femoral access.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
daytime systolic blood pressure assessed by 24 hours ambulatory BP measurement	Changes in mean daytime systolic BP after 3 months is compared between groups. Also the proportion of responders versus nonresponders after 3 months is compared between groups, responders being defined as A) a minimum decrease in daytime systolic BP of 10 mmHg analysis together with and unchanged/increased number of antihypertensive drugs, or B) a decrease in daytime systolic BP of 0-10 mmHg together with a reduced number of antihypertensive drugs.	3 months follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ambulatory 24 hours BP measurements	Systolic, diastolic and mean Blood Pressures at different time points. Daytime and night time BP, dipping status, morning BP surge and BP variation.	1, 3 and 6 months
Echocardiography	Coronary flow reserve (LAD), Diastolic and Systolic ventricular function. LV hypertrophy.	6 months
Biomarkers	Biomarkers concerning renal sodium excretion	1 months
Applanation tonometry	Pulse wave velocity, augmentation index, central BP estimates	6 months
forearm plethysmography	Forearm minimum vascular resistance	6 months

Collaborators and Investigators

• Sponsor: Aarhus University Hospital Skejby
• Collaborators: Aarhus University Hospital; Regional Hospital Holstebro; Regionshospitalet Silkeborg; Randers Regional Hospital; Central Jutland Regional Hospital
• Investigators: Principal Investigator: Ole N Mathiassen, MD, PhD, Aarhus University Hospital, Dep. Cardiology

Publications and helpful links

General Publications

• Peters CD, Mathiassen ON, Vase H, Bech Norgaard J, Christensen KL, Schroeder AP, Rickers HJVH, Opstrup UK, Poulsen PL, Langfeldt S, Andersen G, Hansen KW, Botker HE, Engholm M, Bertelsen JB, Pedersen EB, Kaltoft A, Buus NH. The effect of renal denervation on arterial stiffness, central blood pressure and heart rate variability in treatment resistant essential hypertension: a substudy of a randomized sham-controlled double-blinded trial (the ReSET trial). Blood Press. 2017 Dec;26(6):366-380. doi: 10.1080/08037051.2017.1368368. Epub 2017 Aug 23.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: October 24, 2011
• First Submitted That Met QC Criteria: October 25, 2011
• First Posted (ESTIMATE): October 26, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): September 20, 2016
• Last Update Submitted That Met QC Criteria: September 19, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Treatment Resistant Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: M-20110071