Renal Nerve Denervation in Patients With Hypertension and Paroxysmal and Persistent Atrial Fibrillation (Symplicity AF)

The purpose of this clinical study is to evaluate the feasibility of performing both renal nerve denervation and pulmonary vein isolation on the same patient with the intent of characterizing both safety and effectiveness in a paroxysmal and persistent atrial fibrillation population with hypertension. To assess safety, the study will measure the occurrence of a composite safety endpoint and, to assess effectiveness, the study will measure freedom of chronic treatment failure through a minimum of six months of follow-up.

Study Overview

• Status: Completed
• Conditions: Hypertension; Atrial Fibrillation
• Intervention / Treatment: Device: Arctic Front Advance™ Cardiac Cryoablation System; Device: Symplicity Spyral™ Multi-Electrode Renal Denervation Catheter

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Homburg, Germany, 66421
    • Universitätsklinikum des Saarlandes
• United States
  • California
    • Sacramento, California, United States, 95819
      • Mercy Medical Group-Cardiology
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Marquette, Michigan, United States, 49855
      • UPHS-Marquette
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University Of Pittsburgh Medical Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98122-5711
      • Swedish Medical Center Cherry Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Drug refractory recurrent symptomatic paroxysmal or persistent atrial fibrillation
• Office-based systolic blood pressure of ≥140 mm Hg based despite treatment with 1 or more antihypertensive medications
• Age 18 years to 80 years old.

Key Exclusion Criteria:

• Renal artery anatomy that is ineligible for treatment including: Lacks at least one renal artery for each kidney with ≥3 mm diameter and minimum treatable length per the Spyral Instructions for Use, Renal artery stenosis (>50%) or renal artery aneurysm in either renal artery, A history of prior renal artery intervention including balloon angioplasty or stenting, Renal artery which contain calcification which does not allow at least four radio frequency ablations to be delivered , Diffuse fibromuscular dysplasia (FMD) or FMD which does not allow at least four radio frequency ablations to be delivered; FMD defined as visible beading of the artery on angiography , Unilateral kidney.
• Estimated Glomerular Filtration Rate of <30 mL/min/1.73m2.
• Pregnant, nursing or planning to be pregnant. (Female participants of childbearing potential must have a negative serum or urine human chorionic gonadotropin (hCG) pregnancy test prior to angiography).
• Currently enrolled or plans to participate in a potentially confounding drug or device trial during the course of this study. Co-enrollment in concurrent studies is allowed when documented pre-approval is obtained from the Medtronic study manager.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cryoablation only; Pulmonary vein isolation	Device: Arctic Front Advance™ Cardiac Cryoablation System
Experimental: Cryoablation and renal nerve denervation; Pulmonary vein isolation plus renal nerve denervation	Device: Arctic Front Advance™ Cardiac Cryoablation System; Device: Symplicity Spyral™ Multi-Electrode Renal Denervation Catheter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects in Each Arm That Experience Safety Composite Events	Characterize the rate of safety composite events, (End stage renal disease, Death, Significant Embolic Event, Renal Artery Perforation or Dissection Requiring Intervention, Vascular Complications, Hospitalization for Hypertensive Crisis, New Renal Artery Stenosis, Cardiac Damage, Pulmonary Vein Stenosis, Atrio-Esophageal Fistula, Arrhythmia, Persistent Phrenic Nerve Palsy), within each of the two study arms and also characterize the difference in the rates between study arms. Each event in the composite has its own time frame, either one month or six months post procedure.	Up to one or six months post procedure depending on the event
Proportion of Patients With Chronic Treatment Success	Chronic treatment success is freedom from chronic treatment failure. Chronic treatment failure is defined as the occurrence of either a documented episode of AF lasting 2 or more minutes (as measured by an implantable loop recorder) or an intervention for AF.	Minimum of six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Office Systolic and Diastolic Blood Pressure at 6 Months From Baseline	Compare the difference of office systolic and diastolic blood pressure at 6 months and baseline between study arms.	6 months
Difference in Heart Rate at 6 Months and Baseline	Compare the difference in heart rate using the 6 month follow-up measurement and baseline visit measurement. These values will then be compared between study arms.	6 months
Procedural Measures	Elapsed fluoroscopy time and cryocatheter procedure time between study arms. Renal Denervation Procedure Time and Total Procedural Time will be reported only for the Cryoablation and Renal Denervation group.	Procedure
Proportion of Participants With Symptoms at 6 Months Between Study Arms	The endpoints for this objective are presence of the following arrhythmic symptoms as recorded at the 6-month visit through discussion with the patient at the time of the visit: Dizziness; Palpitations; Rapid heart beat; Dyspnea; Fatigue; Syncope; Other	6 months
Rate of Chronic Treatment Success (Primary Effectiveness Endpoint) for Subjects Off of Class I and III Anti-arrhythmic Drugs Following the Blanking Period.	Compare the rate of chronic treatment success (primary effectiveness endpoint) between study arms for subjects off of Class I and III anti-arrhythmic drugs following the blanking period.	6 months
Percent of Time in AF Burden Over All Follow-up Occurring After the Blanking Period	Compare the Percent of time in AF burden over all follow-up occurring after the blanking period between study arms.	91 days after the cryoablation procedure date until the last Reveal LINQ device data date.

Collaborators and Investigators

• Sponsor: Medtronic Vascular
• Investigators: Principal Investigator: Larry Chinitz, MD, NYU Langone Health

Publications and helpful links

General Publications

• Younis A, Steinberg JS. Renal Denervation for Patients With Atrial Fibrillation. Curr Cardiol Rep. 2021 Jul 16;23(9):126. doi: 10.1007/s11886-021-01558-4.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): April 19, 2021
• Study Completion (Actual): April 19, 2021

Study Registration Dates

• First Submitted: February 13, 2014
• First Submitted That Met QC Criteria: February 13, 2014
• First Posted (Estimated): February 17, 2014

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arrhythmias, Cardiac; Hypertension; Atrial Fibrillation
• Other Study ID Numbers: Symplicity AF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes