FRiEND Registry: Real Life Data From Hypertensive Patients Treated With Renal Denervation in Current Practice in France- French RENal Denervation Registry
Conditions: Hypertension (HTN)
Sponsor: University Hospital, Grenoble

 
 
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SIMPLIFIED PROTOCOL RESEARCH NOT INVOLVING THE HUMAN BEING 
 
TITLE 
Real life data from hypertensive patients treated with renal denervation in current 
practice in France- French RENal Denervation registry 
SHORT TITLE 
FRiEND 
ORGANISATION 
RESPONSIBLE FOR THE 
PROCESSING OF DATA 
CHU GRENOBLE ALPES  
Courriel : DRCI@chu-grenoble.fr 
Téléphone : 04 76 76 59.57 
Adresse : CS 10217, 38043 Grenoble Cedex 09 
Pays : FRANCE 
SCIENTIFIC RESEARCH 
AND IMPLEMENTATION 
COORDINATORS 
Dr Romain Boulestreau 
Cardiologist 
Cardiology Department  
University Hospital Center, Bordeaux 
email : Romain.boulestreau@chu-bordeaux.fr 
Phone : 05-56-79-56-79  
Address :  
Hôpital Haut Leveque av Magellan, 33600 Pessac 
 
Pr Olivier Ormezzano 
Cardiologist 
Hypertension and atherothrombosis 
University Hospital, Michallon, Grenoble, France 
email : oormezzano@chu-grenoble.fr 
Phone : 04-76-76-88-88 
Address : CS 10217 - 38043 Grenoble cedex 09 
 
LIST OF ASSOCIATED 
CENTERS 
7 test centers initially (will be extended to 20 centres in a second phase) 
- 
Centre 
n°1 : 
CHU 
Grenoble 
Alpes : 
Pr 
ORMEZZANO, 
oormezzano@chu-grenoble.fr, 
Cardiology 
department, 
University 
Hospital, Michallon CS 10217 - 38043 Grenoble cedex 09  
- 
Centre /Partenaire n°2 : Dr DOUBLET, julien.doublet@chu-bordeaux.fr, 
Cardiology department, Hôpital Haut-Levèque CHU Bordeaux 1 rue Jean 
Burguet, 33000 Bordeaux-Principal investigator 
- 
Centre /Partenaire n°3 : Pr AZIZI michel.azizi@aphp.fr 
Cardiology department, Hôpital Européen Georges-Pompidou HEGP 

 
 
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20 rue Leblanc. 75015 Paris- Principal investigator 
- 
Centre /Partenaire n°4 :  
Pr COURAND pierre-yves.courand@chu-lyon.fr 
Cardiology department 103 GdR Croix Rousse, 69004 Lyon 
Principal investigator 
- 
Centre /Partenaire n°5 : Pr DUNY BOUHANIC 
Hypertension and Therapeutics Department 
duly-bouhanick.b@chu-toulouse.fr  
Hôpital Rangueil, 1, avenue du Professeur Jean Poulhès - TSA 
50032 - 31059 Toulouse cedex 9 
Principal investigator 
- 
Centre /Partenaire n°6 : Dr DELARCHE 
nicolas.delarche@ch-pau.fr  
Cardiology department 
Hospital center, 4 Boulevard Hauterive- 64000 PAU 
Principal investigator 
- 
Centre /Partenaire n°7 : Dr SILHOL 
Francois.SILHOL@ap-hm.fr  
Cardiology department 
Hôpital de la Timone, 264 rue Saint-Pierre 13385 Marseille 
Principal investigator 
BACKGROUND 
Renal denervation (RDN) is a recent procedure that can be used to control 
BP (blood pressure) in hypertensive patients.  Numerous publications from 
randomised trials have demonstrated the efficacy of RDN in this indication 
(1-14). The latest guidelines now include RDN as an effective technique 
for use in hypertension. Since the beginning of 2023, RDN using 
Medtronic's Spiral radiofrequency system has benefited from transitional 
authorisation for reimbursement by the French health insurance system. An 
application for reimbursement is underway for the ultrasound system. 
We aim to compile an exhaustive prospective register of all procedures 
carried out in France over the next few years, regardless of the type of 
catheter used or the context in which the procedure was carried out 
(transitional reimbursement, industrial register, randomised trial). Our aim 
is to assess the efficacy and safety of the procedure within the French 
healthcare system, the characteristics of patients benefiting from the 
procedure, the centres performing renal denervation, and the care pathways 
used, and to be able to present all this data, independently of the industry, 
to the healthcare authorities when it comes time to reassess the value of this 
procedure and its indications. 

 
 
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PRIMARY OBJECTIVE 
☐ Diagnostics 
☐ Prevention and treatment 
☐ Patient management 
☐ Patient safety 
☐ Organization of healthcare facilities  
☐ Public health policies 
☐ Understanding diseases 
☒Other:To describe changes in SBP evaluated in Home Blood Pressure 
Measurement (HBPM) in hypertensive patients between before and 1 year after 
treatment with RDN. 
PRIMARY ENDPOINT 
Change in SBP measured by HBPM before and after RDN (1 year). 
SECONDARY OBJECTIVES 
SECONDARY OBJECTIVES: 
- To evaluate changes in office systolic blood pressure, the combination of SBP 
measured in HBPM and day ABPM and 24-hour SBP before and 3 months, 6 
months, 1 year, after DNR. 
- Evaluate the evolution at 3 months, 6 months, 1 year, of the drug burden in 
antihypertensive treatment (DDD), the percentage of patients having reached the 
blood pressure target and the win ratio. 
- Evaluate the development of renal artery stenosis before and 6 months, 1 year, 
after DNR. 
- Evaluate the evolution of creatinine levels before and 6 months, 1 year, after 
DNR. 
- Evaluate the occurrence of other complications related to hypertension or to the 
procedure itself. 
- Comparison of responders and non-responders to the procedure (24h ABPM 
systolic blood pressure decrease of 5 mmHg or more and/or the diminution of the 
medical burden by at least one therapeutic class without SBP increase compared 
to baseline). 
- Evaluate the performance of known predictors of response to renal denervation 
in our population. 
- Describe the type of center performing the procedure, the context in which DNR 
is performed, patient characteristics and care pathways. 
METHODOLOGY 
Research that does not involve the human person, as it involves the prospective, 
retrospective, descriptive and comparative use of multicentric data from routine 
care. 
TYPE OF DATA COLLECTED 
The data collected are detailed below: 
• 
Administrative data : 
- centre number followed by a hyphen (-) then the patient's number 
- collection of the patient's non-objection to participate in the FRiEND register 
- date of inclusion, date of procedure 

 
 
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- type of centre carrying out the procedure (hospital, university hospital, clinic, 
ESPIC, other) 
- setting in which the procedure was carried out (day hospitalisation, week 
hospitalisation, conventional hospitalisation) 
 
• 
Personal data : 
- Patient's initials, date of birth (in MM/YYYY format).  
- Gender (male, female, not gendered, refuses to answer), height, weight,  
 
• 
Biological data : 
- 
Biological work-up with measurement of the following parameters: 
Plasma ionogram (Na, K), blood count and platelet count (NFP), proteinuria, 
fasting glycaemia, total cholesterol, LDL cholesterol, HDL cholesterol, 
triglycerides, creatininaemia, estimated glomerular filtration rate (eDFG) 
(according to the Modification of Diet in Renal Disease (MDRD) method), 
uricaemia, microalbuminuria or urinary albumin/creatinine (assessment of target 
organ damage). 
 
• 
Clinical data : 
- Systolic blood pressure (SBP), diastolic blood pressure (DBP), 
heart rate (HR): three measurements will be taken with a validated 
oscillometric electronic device measured according to international 
recommendations (2023ESH-ESC) 
- risk factors (dyslipidaemia, type 2 diabetes, hypertension, 
smoking) 
- cardiovascular (CV) history of more than 6 months (myocardial 
infarction, coronary insufficiency, stroke) 
- non-CV history (cancer, asthma or respiratory insufficiency, 
musculoskeletal disability) 
- ABPM measurement (SBP and DBP for 24 hours, during the day 
and at night) 
- self-measurement of BP (according to the rule of 3 : average of 3 
measurements in the morning and 3 in the evening, 3 consecutive 
days). 
- current treatments (anti-hypertensive, lipid-lowering, anti-
diabetic, anti-platelet). 
- Therapeutic adherence assessment 
 
• 
Imaging data : 
- results of CT scan of renal arteries: number of renal arteries, 
diameter of renal arteries, assessment of possible renal artery 
stenosis (in %) 
- Renal artery echodoppler (if feasible): assessment of possible 
renal artery stenosis (in %), renal artery blood flow velocity. 

 
 
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• 
Procedure: 
- Indication validated by a Centre of Excellence or Blood Pressure 
Clinic (yes/no) 
- Complete secondary hypertension work-up (yes/no) 
- In particular: plasma renin/aldosterone assay? Methoxylated 
catecholamine derivatives? renal artery imaging? 
- Precise indication of the procedure 
- context of treatment (temporary reimbursement of SIMPLICITY 
catheters, registry, randomised study) 
- specialities of the doctor(s) performing the procedure, 
- details of the procedure: under general anaesthetic/analgesia, 
approach,  
- Antithrombotics and anti-platelet aggregants before, during and 
after the procedure 
- number of ablation/sonication points performed 
- volume of contrast medium used, X-ray dosimetry 
- closure system for the approach port 
- complications, if any 
 
• 
Follow-up data : 
- Date and type of follow-up 
- Progress of treatment 
- clinical BP measurements, MAPA and self-measurements 
performed 
- Changes in biological markers 
- Changes in imaging of the renal arteries 
- Complications, if any 
 
This might include retrospective data for patients treated with RDN in the 
past, if investigator believe that the missing data are absent or scarce. As 
we will collect only data coming from a routine care already widely used 
in France for these patients, this should correspond to most of the patients 
already treated with RDN. Patients included retrospectively and 
prospectively will be compared to ensure that there are no selection biaises 
in the retrospective cohort.  
 
Use one or more of the following sensitive variables : 
☐ Country and department of residence of the person studied (NB: the 
collection of the commune of residence (zip code and/or name) is not permitted) 
Pays et département de résidence de la personne étudiée (NB : le recueil de la 
commune de résidence (code postal et/ou nom) n’est pas autorisé) 
☒ Year and month of birth 

 
 
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☒ Date of care (DDMMYYYY) 
☒ Date of death (DDMMYYYY) 
☐ City of death 
☐ None 
 
ORIGIN OF DATA 
 
☒Medical record 
☐ Survey / Cohort / Register not including SNDS data 
☐ Other data 
 
☒ Data from the investigator's department only (coordinating and associated 
centers) 
☐ Data from several departments of the CHU Grenoble Alpes or from a 
department other than that of the investigator (if the investigator is at no time 
involved in the care of the persons targeted by the research). 
DATA COLLECTION 
SCHEDULE 
Prospective and restrospective research : 
- 
3-year register (start of collection april 2025 - end of inclusions april 2027,  
follow-up : 1 year) 
For retrospective patients, data collection will be done from clinical 
database from january 2010. A 4-week delay must be observed between 
the sending of information letters and the start of data collection. 
- 
End of follow-up: april 2028. 
- 
Annual analysis of data from patients who have undergone RDN and 
follow-up at 1 month, 6 months, 1 year after the procedure. 
 
DATA COLLECTION 
Collection : 
The data collected will be those from routine follow-up at 1 month, 6 months, 1 
year of all patients benefiting from a RDN procedure and included in the registry. 
After the procedure, the investigator in each participating centre will manage the 
follow up of the patient. As the study is purely observational, it does not require 
any specific follow-up visits, but includes the collection of data obtained during 
routine follow-up visits. The registry does, however, include data collection at 
fixed times after procedure. The data reported in the Redcap file will be the data 
available closest to the theoretical day of collection.  
Patients who have been lost to follow-up should be investigated through the 
referring doctors to RDN and/or by family members or any other person whose 
name appears on the patient liaison form. In the absence of any information, a 
search for the patient's possible death will be carried out by consulting the 
https://deces.matchid.io/searchqui website, including the INSEE source for deaths 
(the search will be carried out by birth name).  
In case of of the patient's death, the medical record is first checked to ensure 
that the patient has “no objection” to the use of his or her health data for 
research purposes. 
Clinical data collection will be based on the source documents. 
 

 
 
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Codage : 
The data will be pseudonymised by coding: patients will be identified as 
follows: centre number followed by a hyphen (-) then the patient number 
coded number specific to the research indicating the order of inclusion of 
subjects (ex. 01-001).The list of correspondences between the patient code 
and his identity will be kept in each participating center, in the service 
server, by the investigator on an Excel file. 
DATA STORAGE PERIOD 
Personal data relating to persons taking part in research, and processed for this 
purpose, may be kept in the information systems of the controller, the participating 
centre or the healthcare professional involved in the research for a maximum of 2 
years after the last publication of the results of the research or, if there is no 
publication, until the final report of the research is signed. 
The personal data of the professionals involved in the research may not be kept 
for more than fifteen years after the end of the last research project in which they 
participated. 
It is then archived on paper or electronically for a period of time in accordance 
with the regulations in force. The data must then be deleted. 
DESCRIPTION OF 
STATISTICAL ANALYSIS 
OF DATA 
NUMBER OF SUBJECTS TO BE INCLUDED 
The number of subjects included will correspond to the number of patients 
undergoing renal denervation for hypertension at the Grenoble University 
Hospital and in the various French centres participating in the study during the 
study period (the estimation is currently 100 per year). 
 
DATA ANALYSIS 
The database will be stored in accordance with the signed investigator 
commitment, on a secure database certified to keep health data, and linked to the 
REDCAP system supporting the eCRF. The analyses will be carried out at the 
University Cardiology Clinic of the Grenoble University Hospital by Professor 
ORMEZZANO and Dr Romain Boulestreau with the help of the SFHTA, using 
SPSS version 21 (SPSS Corp, Somers, NY) and STATA® 14.1 (Stata 
Corporation, College Station, TX). 
 
Statistical analysis: Absolute values, percentages and means (SD) will be 
calculated to describe the population.  
The differences between the variables before and after the RDN will be tested 
using either a paired t-test for normally distributed data or a Wilcoxon test, and a 
paired Chi2 or a Fisher test. For univariate analysis of variables between the RDN 
responder groups (5 mmHg reduction in 24h SBP) and non-responders, we will 
use the t-student analysis of variance test or non-parametric tests for continuous 
variables, and chi2 or Fisher tests for categorical variables. A multivariate analysis 
will also be performed. 
PEOPLE INCLUDED IN THE 
RESEARCH 
Number of subjects: Estimation of 100 per year (might be less in the first year, 
then more as RDN implementation in France increase) 
 
Inclusion criteria: Adult ( > 18 years old) hypertensive patients treated with RDN 
in France whatever the catheter and the indication. This might include 
retrospective data for patient already treated with RDN in the past.  

 
 
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Non-inclusion criteria: RDN not proposed to the patient, patient opposing the 
collection and use of his/her data for research purposes. 
 
Information and traceability procedures for non-objection/opposition :  
Patients will be fully and fairly informed, in comprehensible terms, of the 
objectives of the study and the nature of the information collected, and of their 
right to object at any time to the use of the data collected. They will be given an 
information letter and the non opposition will be written down in the medical 
records of the patient. If the subject objects to their personal health data being 
processed for research purposes, this objection will be recorded in their medical 
file. This right of objection may be exercised at any time by any means with either 
the person responsible for the research or the establishment holding the data, 
which undertake to respond to the request within a maximum of 2 months. 
Retrospective patients will be informed by post. On receipt of this letter, the 
patient will have 4 weeks to object. 
ETHICS 
NA 
WHY THE STUDY IS IN 
THE PUBLIC INTEREST 
The legal basis for this data processing is Article 6 of the General Data Protection 
Regulation (GDPR), namely the performance of a mission of public interest 
assigned to the data controller and the legitimate interests pursued by it. In 
addition, under Article 9 of the GDPR the data controller may exceptionally 
process special categories of data, including health data notably for scientific 
research purposes. 
EXPECTED BENEFITS 
To objectively evaluate RDN performance, patients and center profiles and care 
pathway in the various French centres participating to the registry, and to 
investigate whether there are any predictive factors (on the basis of the initial 
clinical and biological work-up) for the outcome in terms of lowering blood 
pressure, in order to better target patients who could benefit from this type of 
procedure in the future. 
Provide informed, independent data to the health authorities to support 
reimbursement decisions and the choice of indications.  

 
 
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Study schedule 
Visits 
During 
hospitalization for 
RDN 
1 month 
after 
RDN 
6 
months 
after 
RDN 
12 
months 
after 
RDN 
Patient information   
X 
 
 
 
RDN indication verification 
X 
 
 
 
Blood sample 
X 
 
 
 
Imaging examinations 
X 
 
 
 
Medical history collection 
X 
 
 
 
Clinical examination 
X  
X 
X 
X 
Ongoing therapy collection 
X  
X 
X 
X 
Adverses events recording 
X 
X 
X 
X 
Blood Pressure and heart rate 
recording 
X  
X 
X 
X 
Blood sample 
 
 
 
 
Ionogram (Na, K), glucose level, 
creatininemia (DFG MDRD), 
uricemia 
X 
X 
X 
X 
Total Cholestérol, HDL, LDL 
triglycerides, NFP 
 
 
 
X 
Microalbuminuria, proteinuria 
 
 
 
X 
Clinical examinations 
 
 
 
 
Home Blood Pressure 
Measurement 
 
X 
X 
X 
Ambulatory Blood Pressure 
Measurement 
 
 
 
X 
Renal Arteries ultrasound 
 
 
 
X 
Renal arteries angioCT 
 
 
 
X 
 
 
 
Bibliographie : 
1. Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal 
Denervation for Hypertension (DENERHTN) Trial. Azizi M, Pereira H, Hamdidouche I, Gosse P, Monge M, Bobrie G, 
Delsart P, Mounier-Véhier C, Courand PY, Lantelme P, Denolle T, Dourmap-Collas C, Girerd X, Michel Halimi J, 

 
 
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Zannad F, Ormezzano O, Vaïsse B, Herpin D, Ribstein J, Chamontin B, Mourad JJ, Ferrari E, Plouin PF, Jullien V, 
Sapoval M, Chatellier G; DENERHTN Investigators.Circulation. 2016 Sep 20;134(12):847-57.  
 
2. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant 
hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Azizi M, Sapoval M, Gosse P, 
Monge M, Bobrie G, Delsart P, Midulla M, Mounier-Véhier C, Courand PY, Lantelme P, Denolle T, Dourmap-Collas C, 
Trillaud H, Pereira H, Plouin PF, Chatellier G; Renal Denervation for Hypertension (DENERHTN) investigators. Lancet. 
2015 May 16;385(9981):1957-65 
 
3. Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the 
DENERHTN (Renal Denervation for Hypertension) Trial. Courand PY, Pereira H, Del Giudice C, Gosse P, Monge M, 
Bobrie G, Delsart P, Mounier-Vehier C, Lantelme P, Denolle T, Dourmap C, Halimi JM, Girerd X, Rossignol P, Zannad 
F, Ormezzano O, Vaisse B, Herpin D, Ribstein J, Bouhanick B, Mourad JJ, Ferrari E, Chatellier G, Sapoval M, Azarine 
A, Azizi M; DENERHTN Investigators. J Am Heart Assoc. 2017 Oct 10;6(10). 
 
4. Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation: The DENERHTN 
Study (Renal Denervation for Hypertension). Gosse P, Cremer A, Pereira H, Bobrie G, Chatellier G, Chamontin B, 
Courand PY, Delsart P, Denolle T, Dourmap C, Ferrari E, Girerd X, Michel Halimi J, Herpin D, Lantelme P, Monge M, 
Mounier-Vehier C, Mourad JJ, Ormezzano O, Ribstein J, Rossignol P, Sapoval M, Vaïsse B, Zannad F, Azizi M. 
Hypertension. 2017 Mar;69(3):494-500.  
 
5. Clinic Versus Ambulatory Blood Pressure in Resistant Hypertension: Impact of Antihypertensive Medication 
Nonadherence. A Post Hoc Analysis the DENERHTN Study. Hamdidouche I, Gosse P, Cremer A, Lorthioir A, Delsart 
P, Courand PY, Denolle T, Halimi JM, Girerd X, Ormezzano O, Rossignol P, Pereira P, Azizi M; DENERHTN 
Investigators. Hypertension. 2019 Nov;74(5):1096-1103. 
 
6. Position Paper on the Role of Renal Denervation in the Management of the Difficult-to-Treat Hypertensive Patient. High 
Blood Press Cardiovasc Prev. Bruno RM, Taddei S, Borghi C, et al. Italian Society of Arterial Hypertension (SIIA) 
2020;27(2):109‐117.  
 
7. Renal Denervation in Asia: Consensus Statement of the Asia Renal Denervation Consortium. Kario K, Kim BK, Aoki J, 
et al. Hypertension. 2020;75(3):590‐602. 
 
8. Device-based therapies for arterial hypertension. Lauder L, Azizi M, Kirtane  AJ, Böhm M, Mahfoud F. Nat Rev Cardiol. 
2020 Oct;17(10):614-628.  
 
9. Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with 
uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED 
Expansion) of antihypertensive medications: a novel approach using Bayesian design.Böhm M, Townsend RR, Kario K, 
et al.  Clin Res Cardiol 2020; 109: 289–302. 
 
10. Changes in 24-hour patterns of blood pressure in hypertension following renal denervation therapy. Kario K, Weber MA, 
Mahfoud F, et al. Hypertension 2019: 74: 244–49. 
 
11. REDUCE HTN: REINFORCE. A randomized, sham-controlled trial of bipolar radiofrequency renal denervation for the 
treatment of hypertension. Weber MA, Kirtane AJ, Weir MR, et al. JACC CardiovascInterv 2020; 13: 461–70. 
 
12. Renal denervation in patients with end-stage renal disease and resistant hypertension on long-term haemodialysis. Scalise 
F, Sole A, Singh G, Sorropago A et al.  J Hypertens. 2020 May;38(5):936-942 
 

 
 
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13. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety 
results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Kandzari DE, Böhm M, Mahfoud F, et al. 
Lancet 2018; 391: 2346–55. 
 
14. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive 
medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.Townsend RR, Mahfoud 
F, Kandzari DE, et al.  Lancet 2017; 390: 2160–70.