Effect of Renal Denervation on Atrial Fibrillation

Atrial Fibrillation Clinical Trial

— ERDAF  

Official title:

Effect of Renal Denervation on Atrial Fibrillation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04055285
• Other study ID #: ERDAF
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: August 2019
• Source: Hippocration General Hospital
• Contact: Constantinos P Tsioufis, MD, PhD
• Phone: +30 2132088386
• Email: ktsioufis[@]hippocratio.gr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the ERDAF study (Effect of Renal Denervation on Atrial Fibrillation) is to evaluate the renal sympathetic denervation in patients with resistant arterial hypertension and symptomatic paroxysmal or persistent atrial fibrillation(AF) in order to show if there is a reduction in the AF-related symptoms, the AF recurrence rate, and the total burden (symptomatic and/or asymptomatic) of the arrhythmia. To the best of our knowledge, ERDAF is the first randomized study, which is going to evaluate the effect of RDN [without pulmonary vein isolation (PVI)] on AF recurrence profile and AF ''burden'' using continuous long-term rhythm monitoring via ILRs for a period of 18 months.

Hypothesis

Renal sympathetic denervation in patients with resistant hypertension and symptomatic paroxysmal or persistent atrial fibrillation reduces AF recurrences, total AF "burden" (asymptomatic / symptomatic) and limits the AF-related symptoms.

Description:

In arterial hypertension (AH), a significant proportion of patients, despite the optimal medical therapy, do not achieve adequate blood pressure (BP) control (resistant hypertension). Renal sympathetic denervation (RDN) is a novel alternative minimally invasive therapeutic option for patients with resistant AH. Recent data has shown that RDN with or without pulmonary vein isolation (PVI) may also have a positive impact on the management of patients with paroxysmal or persistent atrial fibrillation (AF). However, there is no randomized study, to date, suggesting that RDN itself (without PVI) reduces the AF recurrences, symptoms, and the total burden of the arrhythmia. The purpose of this study [Effect of Renal Denervation on Atrial Fibrillation (ERDAF)] is to evaluate the RDN (without PVI) in patients with resistant AH and symptomatic paroxysmal or persistent AF in order to show if there is benefit in the incidence of AF recurrences, the total AF burden (symptomatic and asymptomatic) as well as the BP control. This is a single-center, randomized study in which thirty (30) patients with resistant AH and symptomatic paroxysmal or persistent AF will be randomized (1:1) after sinus rhythm restoration and implantation of an implantable loop recorder (ILR), in either RDN (n=15) or conventional treatment of resistant AH with optimal drug therapy (n=15). Patients will be followed-up every three months and for a period of 18 months after the implantation of the ILR. The first three months after RDN will be excluded from our final analysis (blanking period). The primary endpoint will be the change in the total AF burden (Total time in AF during the follow-up period). Secondary endpoints will include the change in the symptomatic and asymptomatic burden of AF, the time to detect the first AF recurrence (symptomatic and/or asymptomatic)-early recurrence of AF after RDN, and the change in BP during the follow-up period.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients >18 years with resistant hypertension [Systolic Blood Pressure (SBP) = 140 mmHg and/or Diastolic Blood Pressure (DBP) = 90 mmHg despite treatment with = 3 antihypertensive drugs of various classes, including a diuretic) and symptomatic paroxysmal or persistent AF will be included in the study after sinus rhythm restoration

Exclusion Criteria:

1. Patients with permanent AF or patients with long-standing persistent AF as defined by the current ESC guidelines for the management of AF1.

2. Patients with a glomerular filtration rate (eGFR)] <45 ml / min / 1.73 m2 calculated using the CKD-EPI43.

3. Patients with secondary arterial hypertension.

4. Patients with an established diagnosis of resistant hypertension <6 months.

5. Patients with severe renal artery stenosis or previous renal artery angioplasty.

6. Patients who have undergone or are about to undergo pulmonary vein isolation.

7. Patients with left end-diastolic ventricle diameter >60 mm in men or >55mm in women.

8. Patients with a left ventricular ejection fraction <35% in the transthoracic echocardiogram (TTE).

9. Patients with AF possible reversible causes (pulmonary embolism, acute coronary syndromes, thyrotoxicosis, alcohol abuse, etc.)

10. Patients with heart failure in NYHA III-IV stage.

11. Patients with life expectancy <1 year.

12. Pregnant women.

13. Patients who are unable to give consent to participate in the study.

14. Patients who do not wish to give written consent to participate in the study.

Related Conditions & MeSH terms

• Arterial Hypertension
• Atrial Fibrillation
• Hypertension

Intervention

Procedure:
• Sympathetic Renal Denervation
Catheter-based sympathetic renal denervation (RDN) using radiofrequency, ultrasound, or perivascular injection of neurotoxic agents such as alcohol has been introduced as a minimally invasive alternative treatment option for patients with resistant hypertension. RDN consists of endovascular catalysis of the kidney sympathetic nerves running in the wall of the renal arteries.

Device:
• Implantable Loop Recorder
Implantable Loop Recorders (ILRs) are small, subcutaneously implanted devices that are able to detect and store atrial fibrillation episodes lasting longer than 2 minutes with high sensitivity (96.1-100%) and good specificity (67-85.4%) for a period of up to three years.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hippocration General Hospital

References & Publications (20)

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Feyz L, Theuns DA, Bhagwandien R, Strachinaru M, Kardys I, Van Mieghem NM, Daemen J. Atrial fibrillation reduction by renal sympathetic denervation: 12 months' results of the AFFORD study. Clin Res Cardiol. 2019 Jun;108(6):634-642. doi: 10.1007/s00392-018-1391-3. Epub 2018 Nov 10. — View Citation

Grassi G, Mark A, Esler M. The sympathetic nervous system alterations in human hypertension. Circ Res. 2015 Mar 13;116(6):976-90. doi: 10.1161/CIRCRESAHA.116.303604. Review. — View Citation

Hindricks G, Pokushalov E, Urban L, Taborsky M, Kuck KH, Lebedev D, Rieger G, Pürerfellner H; XPECT Trial Investigators. Performance of a new leadless implantable cardiac monitor in detecting and quantifying atrial fibrillation: Results of the XPECT trial. Circ Arrhythm Electrophysiol. 2010 Apr;3(2):141-7. doi: 10.1161/CIRCEP.109.877852. Epub 2010 Feb 16. — View Citation

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Kosiuk Md J, Pokushalov Md Phd E, Hilbert Md S, Hindricks Md G, Bollmann Md PhD A, S Steinberg Md J. The Role of Renal Sympathetic Denervation in Atrial Fibrillation. J Atr Fibrillation. 2014 Feb 28;6(5):987. doi: 10.4022/jafib.987. eCollection 2014 Feb-Mar. Review. — View Citation

Lombardi F, Tarricone D, Tundo F, Colombo F, Belletti S, Fiorentini C. Autonomic nervous system and paroxysmal atrial fibrillation: a study based on the analysis of RR interval changes before, during and after paroxysmal atrial fibrillation. Eur Heart J. 2004 Jul;25(14):1242-8. — View Citation

Papademetriou V, Doumas M, Tsioufis K. Renal Sympathetic Denervation for the Treatment of Difficult-to-Control or Resistant Hypertension. Int J Hypertens. 2011;2011:196518. doi: 10.4061/2011/196518. Epub 2011 Mar 30. — View Citation

Papakonstantinou PE, Simantirakis EN. Long-term rhythm monitoring with an implantable loop recorder in patients after the first clinical atrial fibrillation episode. Towards an individualized management. Minerva Cardioangiol. 2019 Apr;67(2):121-130. doi: 10.23736/S0026-4725.19.04883-7. Epub 2019 Feb 5. Review. — View Citation

Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, Shirokova N, Karaskov A, Mittal S, Steinberg JS. A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol. 2012 Sep 25;60(13):1163-70. doi: 10.1016/j.jacc.2012.05.036. Epub 2012 Sep 5. — View Citation

Qiu M, Yin Y, Shan Q. Renal sympathetic denervation versus antiarrhythmic drugs for drug-resistant hypertension and symptomatic atrial fibrillation (RSDforAF) trial: study protocol for a randomized controlled trial. Trials. 2013 Jun 11;14:168. doi: 10.1186/1745-6215-14-168. — View Citation

Simantirakis EN, Papakonstantinou PE, Chlouverakis GI, Kanoupakis EM, Mavrakis HE, Kallergis EM, Arkolaki EG, Vardas PE. Asymptomatic versus symptomatic episodes in patients with paroxysmal atrial fibrillation via long-term monitoring with implantable loop recorders. Int J Cardiol. 2017 Mar 15;231:125-130. doi: 10.1016/j.ijcard.2016.12.025. Epub 2016 Dec 21. — View Citation

Simantirakis EN, Papakonstantinou PE, Kanoupakis E, Chlouverakis GI, Tzeis S, Vardas PE. Recurrence rate of atrial fibrillation after the first clinical episode: A prospective evaluation using continuous cardiac rhythm monitoring. Clin Cardiol. 2018 May;41(5):594-600. doi: 10.1002/clc.22904. Epub 2018 May 14. — View Citation

Tsioufis C, Dimitriadis K, Kasiakogias A, Kalos T, Liatakis I, Koutra E, Nikolopoulou L, Kordalis A, Ella RO, Lau EO, Grassi G, Papademetriou V, Tousoulis D. Effects of multielectrode renal denervation on elevated sympathetic nerve activity and insulin resistance in metabolic syndrome. J Hypertens. 2017 May;35(5):1100-1108. doi: 10.1097/HJH.0000000000001262. — View Citation

Tsioufis C, Ziakas A, Dimitriadis K, Davlouros P, Marketou M, Kasiakogias A, Thomopoulos C, Petroglou D, Tsiachris D, Doumas M, Skalidis E, Karvounis C, Alexopoulos D, Vardas P, Kallikazaros I, Stefanadis C, Papademetriou V, Tousoulis D. Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry. Clin Res Cardiol. 2017 May;106(5):322-330. doi: 10.1007/s00392-016-1056-z. Epub 2016 Dec 12. Erratum in: Clin Res Cardiol. 2017 May;106(5):392. — View Citation

Vollmann D, Sossalla S, Schroeter MR, Zabel M. Renal artery ablation instead of pulmonary vein ablation in a hypertensive patient with symptomatic, drug-resistant, persistent atrial fibrillation. Clin Res Cardiol. 2013 Apr;102(4):315-8. doi: 10.1007/s00392-012-0529-y. Epub 2012 Dec 14. — View Citation

Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; ESC Scientific Document Group . 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-3104. doi: 10.1093/eurheartj/ehy339. — View Citation

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change in the total AF "burden" (symptomatic and asymptomatic AF burden) during the follow-up period.	AF "burden": The amount of time (minutes or hours) the patient is in AF out of the total follow-up period.	From 3 months to 18 months.The first three months after RDN will be excluded from our final analysis (blanking period)
Secondary	Change in the symptomatic AF "burden" during the follow-up period.	Symptomatic AF ''burden'': The amount of time (minutes or hours) in which the patient is in AF, perceived by the patient AF, out of the total follow-up period.	From 3 months to 18 month.The first three months after RDN will be excluded from our final analysis (blanking period)
Secondary	Change in asymptomatic AF "burden" during the follow-up period.	Asymptomatic AF "burden": The amount of time (minutes or hours) in which the patient is in AF that the patient does not perceive out of the total follow-up period.	From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period)
Secondary	The time interval for the detection of the first AF recurrence after the ILR implantation during the follow-up period.		From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period)
Secondary	The time interval for detection of the first symptomatic recurrence of the arrhythmia after the ILR implantation during the follow-up period.		From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period)
Secondary	Change in blood pressure (systolic, diastolic, and mean blood pressure) as measured by 24-hour ambulatory blood pressure monitoring (ABPM) during the follow-up period.		From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period)
Secondary	Change in office blood pressure (systolic, diastolic).		From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period)