Renal Protection Using Sympathetic Denervation in Patients With Chronic Kidney Disease

NCT ID: NCT02002585

Last Updated: 2013-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2018-12-31

Brief Summary

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Kidney protection study (KPS 1) is a prospective randomized clinical study comparing the use of renal denervation (RDN) and optimal medical therapy in subjects with chronic kidney disease stage 3-4 and resistant arterial hypertension to optimal medical therapy alone. Renal denervation is a modern endovascular method used to treat resistant hypertension. The method is being extended to other groups of patients, where the sympathetic tone is increased beyond resistant hypertension. Because of the character of the disease, we hypothesize that renal denervation can reduce or prevent progressive deterioration of kidney functions in this patient population. The aim of this clinical study is to show that renal denervation has protective effects on the progression of chronic renal insufficiency.

Detailed Description

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Background:

patients with chronic renal insufficiency are an ideal group for renal denervation (RDN), because of the increase in sympathetic tone. This increase leads to sodium retention, reduction of perfusion of the kidney and to excessive activation of renin angiotensin aldosterone system. The activation of the sympathetic system significantly contributes to the progression of chronic renal insufficiency. The consequences the hyperactivity of the sympathetic system are affected by selective renal sympathectomy. RDN demonstrably reduces retention of sodium, reduces the production of renin and significantly reduces renal vascular resistance. Furthermore, RDN reduces microalbuminuria and renal podocyte damage in experimental model. RDN also improves renal function in the model of acute Glomerulonephritis. In patients with resistant hypertension and preserved renal function, it was also shown that renal denervation improves renal resistant index and significantly decreases microalbuminuria. The procedure was found to be safe in all studies with renal denervation and was not associated with deterioration of renal function. Several experimental data exist on the effectiveness of RDN in chronic renal insufficiency. In a model of acute renal failure in mouse (endotoxemia model), it was shown that RDN has protective effect on renal function. The decline in the glomerular filtration during endotoxemia was significantly lower in the group treated with RDN compared to the control group. In addition, the renal flow during acute renal failure after RDN was improved. In the model of heart failure in mice, it has been shown that RDN in combination with olmesartan reduces albuminuria and the damage of podocytes and also reduces the levels of renal norepinephrine, angiotensinogen, angiotensin II, and the level of oxidative stress.

Very few data on the effect of RDN on renal function in human were also published. Renal damage in hypertensives subject was not found after RDN with the Symplicity system more than 3 years post procedure. Mahfoud and coworkers showed that subject treated with RDN had lower blood pressure and renal resistive index and at the same time stabilize their renal function. The number of patients with microalbuminuria or macroalbuminuria decreased significantly one year after RDN.

RDN has also positive effect on albuminuria and proteinuria in patients with preserved renal function. The first studies performed in patients with chronic kidney disease (CKD stage 3-4) and resistant hypertension was done by Hering et coworkers. In this study, 15 patients with an average eGFR of 31ml/min/1, 73m2 underwent RDN. The authors were able to show that RDN effectively lowers blood pressure and was not associated further deterioration of renal function. RDN had other positive effects on hemoglobin concentration , proteinuria and on BNP levels. Moreover, the augmentation index of peripheral arteries was also improved by RDN. This work showed multiple effects of RDN beyond the reduction of blood pressure. We, therefore think that patient with chronic kidney disease are good candidates for RDN. However, the mentioned study has a relatively short term follow up (6 months to one year) and does not have a comparative arm.

Aim of study :

our proposed trial aimed to show that RDN not only contribute to improve the control of blood pressure in patients with resistant hypertension but also has protective effects on kidney function in subjects with chronic kidney disease. Our trial will have a comparative arm and will last 3 years.

Planned intervention:

The two strategies that are going to be compared are optimal medical therapy against optimal medical therapy with renal denervation.

Conditions

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Arterial Hypertension Chronic Renal Insufficiency

Keywords

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Renal protection Renal sympathetic denervation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RDN and optimal medical therapy

Renal denervation will be performed using the available denervation device with a european approval according to current guidelines. The same device will be used for all patients in this arm to avoid efficacy bias.

Group Type EXPERIMENTAL

Renal denervation

Intervention Type PROCEDURE

Catheter based renal sympathetic denervation is a endovascular method used for the treatment of resistent hypertension.

optimal medical therapy alone

Group of patients who will be treated only with optimal medical therapy and will not be denervated. Subsequently, the patients will be followed in our cardiology and nephrology department according to the study flowchart for 3 years according to the standard of care in our institution for patients with chronic renal insufficiency.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Renal denervation

Catheter based renal sympathetic denervation is a endovascular method used for the treatment of resistent hypertension.

Intervention Type PROCEDURE

Other Intervention Names

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RDN - Renal sympathetic denervation

Eligibility Criteria

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Inclusion Criteria

* Signed informed consent
* Age between 18-80 years
* Chronic renal insufficiency in CKD 3-4 from nephrologist (eGFR (MDRD) ≤ 45 ml/min/1.73 m2)
* Arterial hypertension treated with:

systolic BP ≥ 140 mmHg + at least 3 antihypertensive drugs Including a diuretic systolic BP ≥ 135 mmHg + 3 antihypertensives Including a diuretics + diabetes mellitus type 2.

systolic BP ≥ 130 mmHg on 24 hr ABPM + 3 antihypertensive drugs Including a diuretics

• Renal artery diameter ≥ 4 mm according to the renal angiography (documented on quantitative renal angiography), renal artery length at least 20mm

Exclusion Criteria

* Secondary hypertension
* White coat hypertension
* abnormalities in renal angiogram disqualifying for RDN
* Life expectancy \< 1 year
* Type 1. Diabetes mellitus
* Significant stenotic valvular heart disease
* Acute coronary syndrome of unstable angina in the past 6 months
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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General University Hospital, Prague

OTHER

Sponsor Role collaborator

Na Homolce Hospital

OTHER

Sponsor Role collaborator

Mount Sinai Hospital, New York

OTHER

Sponsor Role collaborator

Charles University, Czech Republic

OTHER

Sponsor Role lead

Responsible Party

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Ass. prof. Jean-Claude M. Lubanda, MD, Ph.D

Associate professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jean Claude Lubanda, Ass.Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Charles University, Czech Republic

Locations

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Charles University in Prague

Prague, , Czechia

Site Status RECRUITING

Countries

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Czechia

Central Contacts

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Jean Claude Lubanda, Ass.Prof. MD

Role: CONTACT

Phone: +420224962692

Email: [email protected]

Facility Contacts

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Jean Claude Lubanda, Ass.Prof.MD

Role: primary

Martina Striteska, Mgr.

Role: backup

Other Identifiers

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KPS1

Identifier Type: -

Identifier Source: org_study_id