Renal Denervation + PVI vs PVI Alone for Persistent AF

NCT ID: NCT05116384

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-30
• Study Completion Date: 2026-06-30

Brief Summary

Pulmonary vein isolation (PVI) is the cornerstone of ablation for atrial fibrillation (AF). Increased cardiac sympathetic stimulation can facilitate AF and reduction can be accomplished by renal artery denervation (RDN). The recently completed randomized trial, ERADICATE-AF, convincingly demonstrated that RDN plus PVI resulted in a reduction in recurrent incident AF for uncontrolled hypertensives.

This is a randomized controlled pilot trial, "To Evaluate Renal Artery Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation" (ERADICATE-AF II) to test if RDN plus PVI enhances long-term efficacy vs PVI for persistent AF patients with controlled or without hypertension using implantable loop recordings.

Detailed Description

Pulmonary vein isolation (PVI) is the cornerstone of ablation strategies for atrial fibrillation (AF) and is the only cardio-centric approach consistently shown to be effective for reducing arrhythmia recurrence and improving symptom status. Catheter ablation is superior to medical therapy and current antiarrhythmic drug options are limited, can have significant adverse effects, and are associated with a high arrhythmia recurrence rate, especially for persistent AF. Catheter ablation is now commonly prescribed for symptomatic AF patients who do not respond to medications and carries a class II indication. Thousands of patients undergo catheter ablation in the US each year. Nonetheless, even with technical advances, PVI has a recognized and significant rate of short- and long-term failure, and often requires multiple procedures to establish success.

The mechanisms of AF are diverse, but increased central sympathetic outflow and efferent cardiac sympathetic nerve stimulation can lead to enhanced automaticity and triggered activity, and thus contribute to the development and perpetuation of AF. Reduction in cardiac sympathetic input has been proposed as a logical adjunctive approach to PVI but its technical application via cardiac ablation (targeting autonomic ganglia) has had mixed results at best.

The therapeutic objective of lesser cardiac sympathetic stimulation can be potentially accomplished by renal artery denervation (RDN), a technique originally developed for the treatment of resistant hypertension. RDN's potential for antiarrhythmic effect may be mediated by reduced central nervous sympathetic output and is exemplified by a decrease in whole-body norepinephrine spillover and muscle-sympathetic nerve activity.

The recently completed large-scale, randomized, multicenter, single-blind clinical trial, ERADICATE-AF, demonstrated that RDN plus PVI resulted in a relative 43% reduction (absolute change, 15%; P < 0.001) in recurrent incident AF during one year of follow-up. The trial enrolled > 300 patients with paroxysmal AF referred for ablation, all with poorly controlled hypertension despite medication. There was no difference in complications between the 2 groups, and the procedure with RDN was only lengthened by about 24 minutes.

The trial results suggested that a strategy of reducing cardiac autonomic input is an effective antiarrhythmic approach, in line with many preclinical models. It also represents a paradigm of the potential for complementary noncardiac ablation that is effective and safe when coupled with PVI. Until now, this approach has only been tested in patients with resistant and/or poorly controlled hypertension.

A randomized controlled pilot clinical trial has been proposed: "A Trial to Evaluate Renal Artery Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation" (ERADICATE-AF II), to test the hypothesis that RDN in addition to PVI enhances long-term antiarrhythmic efficacy in comparison to PVI alone for patients with persistent AF with controlled hypertension or without hypertension in a multicenter, single-blinded, longitudinal randomized clinical trial. The trial will be advantaged by performing implantable loop recordings (ILR) in all patients, which will facilitate the calculation of AF burden, now recognized as a powerful predictor of clinical outcome. With successful completion of this pilot program, we hope to launch a large-scale trial with cardiovascular and death events as endpoints.

The primary aim of the study:

To determine if patients with persistent AF with controlled hypertension or without hypertension who are referred for catheter ablation (PVI) and undergo adjunctive RDN have reduced AF burden at 12 months in comparison to patients who undergo only PVI

The following secondary aims will be tested:

In patients with persistent AF with controlled hypertension or without hypertension who are referred for catheter ablation (PVI) and undergo adjunctive RDN relative to patients who undergo only PVI:

1. To assess safety, blood pressure and autonomic nervous system outcomes

1. Procedural complications rates

2. Postural blood pressure changes over time

3. Ambulatory blood pressure monitor results

4. Cardiac sympathetic nervous system modulation

2. To evaluate clinical end points

1. Frequency of progression to recurrent persistent AF

2. Referral for repeat catheter ablation of AF

3. Need for cardiovascular emergency room visits and hospitalizations

3. To measure effects on quality of life

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Pulmonary vein isolation

Electrical isolation by cryoballoon of all pulmonary veins

Group Type: ACTIVE_COMPARATOR

catheter ablation

Intervention Type: DEVICE

cryo energy via cryoballoon

Pulmonary vein isolation + renal artery denervation

After completion of the standard PVI, radiofrequency ablation of bilateral renal arteries

Group Type: EXPERIMENTAL

catheter ablation

Intervention Type: DEVICE

cryo energy via cryoballoon

renal artery denervation

Intervention Type: DEVICE

RF energy delivery to multiple sites within each major renal artery

Interventions

catheter ablation

cryo energy via cryoballoon

Intervention Type: DEVICE

renal artery denervation

RF energy delivery to multiple sites within each major renal artery

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years

2. Symptomatic persistent AF eligible for referral for PVI based on current guidelines1 (persistent AF defined as continuation > 7 days and up to 1 year)

3. No prior history of HTN or HTN controlled on medical therapy (defined as SBP <140 mm Hg and DBP <85 mm Hg)

4. Renal vasculature accessible as determined by pre-procedural renal magnetic resonance angiogram

5. Willingness to undergo ILR placement

6. Willingness to comply with post-procedural follow-up requirements and to sign informed consent.

Exclusion Criteria

1. Inability to undergo AF catheter ablation (e.g., presence of a left atrial thrombus, contraindication to all anticoagulation)

2. Prior left atrial ablation for an atrial arrhythmia

3. NYHA class IV congestive heart failure or LVEF < 25%

4. Paroxysmal AF, or longstanding persistent AF (duration > 1 year)

5. Coronary revascularization or valve surgery within 3 months

6. Prior valve surgery using a mechanical prosthesis

7. Renal artery anatomy that is ineligible for treatment including:

1. Predicted inability to access renal vasculature

2. Main renal arteries < 4 mm in diameter or < 20 mm in length.

3. Hemodynamically or anatomically significant renal artery abnormality or stenosis

4. A history of prior renal artery intervention including balloon angioplasty or stenting that precludes a possibility of ablation treatment

5. Multiple main renal arteries to either kidney

8. An estimated glomerular filtration rate (eGFR) < 45mL/min/1.73m2, using the MDRD calculation

9. Life expectancy <1 year for any medical condition

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Steinberg

Professor of Medicine (adj)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Rochester

Short Hills, New Jersey, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jonathan Steinberg, MD

Role: CONTACT

jsteinberg@smgnj.com

9734364155

Facility Contacts

Jonathan Steinberg

Role: primary

jsteinberg@smgnj.com

9734364155

References

Steinberg JS, Shabanov V, Ponomarev D, Losik D, Ivanickiy E, Kropotkin E, Polyakov K, Ptaszynski P, Keweloh B, Yao CJ, Pokushalov EA, Romanov AB. Effect of Renal Denervation and Catheter Ablation vs Catheter Ablation Alone on Atrial Fibrillation Recurrence Among Patients With Paroxysmal Atrial Fibrillation and Hypertension: The ERADICATE-AF Randomized Clinical Trial. JAMA. 2020 Jan 21;323(3):248-255. doi: 10.1001/jama.2019.21187.

Reference Type: RESULT

PMID: 31961420 (View on PubMed)

Other Identifiers

R34HL153579

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UR ERADICATE-AF II

Identifier Type: -

Identifier Source: org_study_id