Clinical trial NCT02482103: The Dutch National Renal Denervation Registry
Official title: Safety, Success Rate and Long Term Consequences of Renal Denervation in Patients With Therapy Resistant Hypertension. The Dutch National Renal Denervation Registry
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hypertension
Keywords: Therapy resistant hypertension
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Dutch Kidney Foundation
First posted: 2015-06-26
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients treated with (or evaluated and refused for) renal denervation in Dutch hospitals. Indications for RD (by Dutch consensus) are therapy resistant hypertension defined as a blood pressure above treatment goal despite use of 3 or more antihypertensive agents preferably including a diuretic or intolerance for (additional) antihypertensives. Secondary hypertension is excluded beforehand.

Brief summary: This study is a national registry of patients treated with renal denervation (RD) in the Netherlands.

The aim of the study is to collect data on safety of the procedure, predictors of the blood pressure lowering effect, sustainability of the effect and to assess the cardiovascular event rate in patients treated with renal denervation.

This is a prospective observational study.

Detailed description: Hypertension is common and one of the major risk factors for cardiovascular disease. Therefore, it is a major societal and economic health problem. A substantial proportion (20-40%) of the treated hypertensive patients has sub-optimal blood pressure control despite the use of multiple drugs. All these patients have an increased cardio-vascular risk. Furthermore, the use of multiple drugs diminishes compliance to treatment, and increases the risk of side effects. This underscores the need for new approaches for hypertension management. Elevated (renal) sympathetic nerve activity contributes importantly to the development of hypertension and subsequent vascular risk. Deliberate disruption of sympathetic nerve activity (sympatholytic therapy) leads to improvement of vascular outcome through blood pressure dependent and blood pressure independent effects. Recently, a promising novel sympatholytic approach has been introduced, i.e. catheter-based renal denervation in a small clinical trial with resistant hypertensive patients. Many clinical centres have now started to perform this procedure or are in the process to start up.

The Dutch Minister of Health has decided to allow renal denervation in patients with so called resistant hypertension, and "conditional reimbursement" is available starting Jan 1st 2013 for a maximum of 4 years. The Netherlands Organisation for Health Research and Development (ZonMw) has provided us with a grant to perform a randomized trial (SYMPATHY) to evaluate the effect on blood pressure at 6 months after intervention. Maximum follow-up in this trial will be 2 years. Important limitations of this study are, firstly that that follow-up is limited to 2 years after renal denervation. Secondly, not all patients that undergo renal denervation, will participate in the abovementioned trial. The Dutch National Renal Denervation Registry will complement the information from the trial in several aspects. These deal with safety, non-responders, and sustainability.

Objectives of the national database are to collect data that will deliver information on:

Safety:

1. What are the short and long term procedural related complications?

   Responders
2. What are the predictors for the effect on blood pressure, in particular patient related factors and procedural related factors?
3. Are there differences between the various renal denervation devices?

   Sustainability
4. What is the effect on blood pressure after (3), 6, (9), 12, (18), 24, (30), 36, and 60 months and thereafter in patients who are considered eligible based on the judgement of the treating physician?
5. What is the effect on kidney function after (3), 6, (9), 12, (18), 24, (30), 36, and 60 months and thereafter in patients who are considered eligible based on the judgement of the treating physician?
6. What are the cardiovascular events rates in this population, in strata of achieved blood pressure level, and potentially compared with other populations.

Methods:

With this database a nationwide cohort is build comprising patients treated with renal denervation over the years, with uniform baseline data collection and uniform follow-up measurements in terms of safety measurements, blood pressure measurements, hospitalisations, cardiovascular outcomes and all-cause mortality. The data collection will occur through a web-based data entry application. All centers in the Netherlands that perform renal denervation will be asked to participate. All patients who underwent renal denervation should be included, irrespective of the reason and device used.

To address the outstanding research questions specific statistical analyses plans will be applied.

Conclusion:

Our expected results are:

1. to be able to identify patients characteristics, which are associated with a high probability of a favourable blood pressure response to renal denervation,
2. to provide short-and long-term (24 -60 months) side effects of renal denervation

Perspective:

These results, collected in routine clinical practice in a large number of clinics in the Netherlands, will have a major impact on the treatment of 'resistant hypertension'. The safety and efficacy data will pave the way for formal cost-effectiveness analyses. The data have the potential to be of high relevance to decision and policy makers in the government and health insurances. When deemed cost-effective and safe, this approach will be widely used in the treatment of 'resistant hypertension' and will revolutionise the treatment of these patients. Furthermore, it will open ways for evaluation of other groups of patients characterized by a high sympathetic tone; in particular patients with less severe hypertension, heart failure and chronic kidney disease.

Eligibility criteria: Inclusion Criteria:

* treated with renal denervation. The decision to perform the procedure was made by the treating physician in the participating hospitals

Exclusion Criteria:

* below age of 18 years

Primary outcomes:
measure: Change in blood pressure
timeFrame: 6 months
Secondary outcomes:
measure: safety aspects (change in renal function)
timeFrame: 5 years
measure: safety aspects: long term kidney function
timeFrame: 5 years
measure: longterm consequences: CVD events
timeFrame: 5 years
measure: safety aspects: procedures complication
timeFrame: 1 year
measure: longterm consequences: kidney function
timeFrame: 5 years
measure: longterm consequences: mortality
timeFrame: 5 years
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: Julius Center for Health Sciences and Primary Care
name: Michiel L. Bots, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vink EE, Bots ML, Blankestijn PJ. Renal denervation as therapy for hypertension: potentials and unanswered questions. Eur J Prev Cardiol. 2013 Dec;20(6):980-91. doi: 10.1177/2047487312473019. Epub 2012 Dec 19.
citation: Verloop WL, Vink EE, Spiering W, Blankestijn PJ, Doevendans PA, Bots ML, Vonken EJ, Voskuil M, Leiner T. Effects of renal denervation on end organ damage in hypertensive patients. Eur J Prev Cardiol. 2015 May;22(5):558-67. doi: 10.1177/2047487314556003. Epub 2014 Oct 17.
citation: Vink EE, Verloop WL, Bost RB, Voskuil M, Spiering W, Vonken EJ, Bots ML, Blankestijn PJ. The blood pressure-lowering effect of renal denervation is inversely related to kidney function. J Hypertens. 2014 Oct;32(10):2045-53; discussion 2053. doi: 10.1097/HJH.0000000000000282.
citation: Verloop WL, Vink EE, Spiering W, Blankestijn PJ, Doevendans PA, Bots ML, Vonken EJ, Voskuil M. Renal denervation in multiple renal arteries. Eur J Clin Invest. 2014 Aug;44(8):728-35. doi: 10.1111/eci.12289.
citation: Verloop WL, Vink EE, Voskuil M, Vonken EJ, Rookmaaker MB, Bots ML, Doevendans PA, Blankestijn PJ, Spiering W. Eligibility for percutaneous renal denervation: the importance of a systematic screening. J Hypertens. 2013 Aug;31(8):1662-8. doi: 10.1097/HJH.0b013e328362152e.
citation: Persu A, Jin Y, Baelen M, Vink E, Verloop WL, Schmidt B, Blicher MK, Severino F, Wuerzner G, Taylor A, Pechere-Bertschi A, Jokhaji F, Fadl Elmula FE, Rosa J, Czarnecka D, Ehret G, Kahan T, Renkin J, Widimsky J Jr, Jacobs L, Spiering W, Burnier M, Mark PB, Menne J, Olsen MH, Blankestijn PJ, Kjeldsen S, Bots ML, Staessen JA; European Network Coordinating research on REnal Denervation Consortium. Eligibility for renal denervation: experience at 11 European expert centers. Hypertension. 2014 Jun;63(6):1319-25. doi: 10.1161/HYPERTENSIONAHA.114.03194. Epub 2014 Mar 24.