Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02002585
Other study ID # KPS1
Secondary ID
Status Recruiting
Phase Phase 2
First received November 25, 2013
Last updated December 1, 2013
Start date November 2013
Est. completion date December 2018

Study information

Verified date December 2013
Source Charles University, Czech Republic
Contact Jean Claude Lubanda, Ass.Prof. MD
Phone +420224962692
Email Jean-Claude.Lubanda@vfn.cz
Is FDA regulated No
Health authority Czech Republic: Ethics Committee
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date December 2018
Est. primary completion date June 2018
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 80 Years
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

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

Locations

Country Name City State
Czech Republic Charles University in Prague Prague

Sponsors (4)

Lead Sponsor Collaborator
Charles University, Czech Republic General University Hospital, Prague, Mount Sinai Hospital, New York, Na Homolce Hospital

Country where clinical trial is conducted

Czech Republic, 

Outcome

Type Measure Description Time frame Safety issue
Primary The changes of eGFR by MDRD The changes of the value of eGFR measured using the MDRD equation in both groups measure at baseline and after 6 months 6 months Yes
Primary Changes in proteinuria (Microalbuminuria) in 6 months the change in the value of proteinuria expressed in g/24hrs or microalbuminuria expressed in ug/24hrs measured at baseline compared to value at 6 month in both study groups 6 months Yes
Primary Changes in the value of Cystatin C Changes in the value of Cystatin C measure at baseline and after 6 months in both groups 6 months Yes
Primary Time to the development of end-stage renal disease (ESRD)/Hemodialysis The time to the development of end-stage renal disease (ESRD)/Hemodialysis in both groups 3 years Yes
Primary combined renal endpoint the combination of all primary outcomes measured compared to baseline in both groups 6 months Yes
Secondary Total mortality the total mortality in both groups at 6 months, 2 years and 3 years 3 years No
Secondary The total cardiovascular mortality the total cardiovascular mortality in 6 months, 2 years and 3 years in both groups 3 years No
Secondary total renal mortality the total renal mortality in both arms at 6 months, 2 years and 3 years 3 years No
Secondary changes in blood pressure the changes of systolic and diastolic blood pressure at 6 months, 1, 2 and 3 years measured as office blood pressure, home blood pressure monitoring and ambulatory blood pressure monitoring (ABPM) from baseline in both arms 3 years Yes
Secondary •Changes in concentration of Blood urea Nitrogen (BUN) , creatinine in 6 months, 3 years the changes in concentration of blood urea Nitrogen (BUN) and creatinine in 6 months, 1, 2 and 3 years in both arms 3 years Yes
Secondary albumin-creatine ratio Albumin-Creatinine-Ratio (mg/mmol) in 6 months, 1, 2 and 3 years in both arms 3 years Yes
Secondary changes in cardiac structure and function the changes in cardiac structure and function assessed by echocardiography (left ventricular mass, left ventricular ejection fraction, left ventricular diastolic function) at 6 months, 1, 2 and 3 years in both arms. 3 years No
Secondary the changes in renal resistive index •the changes in renal resistive index (RRI) measured using renal duplex ultrasound at 6 months, 1, 2 and 3 years in both groups 3 years No
See also
  Status Clinical Trial Phase
Recruiting NCT05684055 - "Community-based, eHealth Supported Management of Cardiovascular Risk Factors by Lay Village Health Workers (ComBaCaL aHT TwiC 1 & ComBaCaL aHT TwiC 2) N/A
Active, not recruiting NCT05436730 - "Escape" Phenomenon of the Antihypertensive Therapy Efficacy
Not yet recruiting NCT03294070 - Fimasartan Plus Amlodipine on Hemodynamic Parameters and Arterial Stiffness in Patients With Hypertension Phase 4
Recruiting NCT01959997 - Comparison of Redo PVI With vs. Without Renal Denervation for Recurrent AF After Initial PVI Phase 2
Completed NCT00983632 - Selective Vagus Nerve Stimulation in Human N/A
Recruiting NCT06098300 - Effects of Change in Blood Pressure on Retinal Capillary Rarefaction in Patients With Arterial Hypertension
Completed NCT04564118 - A Retrospective Analysis of the Adherence to Clinical Practice Guidelines Using the "MedicBK" Digital Platform in Patients With Hypertension and Atrial Fibrillation
Terminated NCT04677322 - TO ASSESS THE EFFECTIVENESS OF THE INTERVENTION OF THE LOW-SODIUM DIET IN PATIENTS WITH HTA
Completed NCT04278001 - Clinical Usefullness of the Cuffless SOMNOtouch NIBP Device for 24-hour Ambulatory Blood Pressure Measurement N/A
Withdrawn NCT03047538 - Fixed Combination for Lipid and Blood Pressure Control Phase 4
Completed NCT03046264 - Invasive Validation of Non-invasive Central Blood Pressure Measurements Using Oscillometric Pulse Wave Analysis N/A
Completed NCT02620995 - Effects of Sildenafil on Penile Vascular Function in Hypertensive Men With Erectile Dysfunction Phase 4
Completed NCT02041832 - Detection of Subclinical Atrial Fibrillation in High Risk Patients Using Implantable Loop Recorder N/A
Completed NCT01459120 - Comparison of Door-to-door Versus Community Gathering to Provide HIV Counseling and Testing Services in Rural Lesotho N/A
Completed NCT01546181 - Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
Recruiting NCT01132001 - Ambulatory Versus Home Blood Pressure Measurement N/A
Completed NCT01454583 - Registry for Ambulant Therapy With RAS-Inhibitors in Hypertension-patients in Germany N/A
Recruiting NCT03917758 - Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors N/A
Completed NCT03722524 - The Use of TrIple Fixed-dose Combination in the Treatment of Arterial Hypertension
Completed NCT03539627 - Azilsartan Medoxomil in Hypertensive pAtients With Stable Ischemic Heart Disease and DiabEtes MEllitus.