NCT03228823

Brief Summary

Premature ventricular contractions (PVCs) coexist in patients with heart failure (HF) and LV dysfunction. Frequent PVCs have shown to induce a reversible cardiomyopathy (PVC-CM). This clinical pilot study will enroll 36 patients with frequent PVCs (burden \>10%) and CM (LVEF \<45%) and randomize them to either: 1) RFA or 2) AADs. Prior to treatment, patients will undergo a baseline cardiac MR if clinically indicated followed by 3-month observation period (optimal HF medical therapy). Changes in LV function/scar, PVC burden/arrhythmias and clinical/functional status (QOL, HF symptoms and admissions, NYHA class) and adverse events will be assessed throughout the observation period and compare with PVC suppression strategies (RFA or AAD). Similar comparison will be made between RFA and AAD treatment groups during a 12-month follow up using a Prospective Randomized Open, Blinded End-point (PROBE) study design. The treatment regimens will be compared in an intention-to-treat analysis. In addition, a total of 20,000 consecutive ambulatory ECG Holter monitors from all participating centers will be screened to identify all patients with probable diagnosis of PVC-CM. This pilot study is intended to estimate the prevalence of this clinical entity and pave the way for a large full scale randomized trial to identify best treatment strategy for patients with PVC-CM. Treating and reversing this underestimated PVC-CM may improve patient's health and subsequently decrease HF healthcare spending.

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
5

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Aug 2018

Typical duration for phase_4

Geographic Reach
2 countries

11 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 18, 2017

Completed
7 days until next milestone

First Posted

Study publicly available on registry

July 25, 2017

Completed
1 year until next milestone

Study Start

First participant enrolled

August 1, 2018

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2021

Completed
Last Updated

April 14, 2021

Status Verified

April 1, 2021

Enrollment Period

3.1 years

First QC Date

July 18, 2017

Last Update Submit

April 13, 2021

Conditions

Keywords

Premature Ventricular contractionsCardiomyopathy

Outcome Measures

Primary Outcomes (2)

  • Improvement of left ventricular ejection fraction after PVC suppression

    Compare the overall improvement or change in LVEF between RFA and AAD groups.

    12 months

  • Responders to PVC suppression strategy

    Assessment of the number of responders (delta LVEF ≥ 10%) after PVC suppression strategies will assess the effectiveness of RFA and AADs to reverse or improve cardiomyopathy induced by frequent PVCs.

    12 months

Secondary Outcomes (3)

  • Successful PVC suppression

    12 months

  • Composite Adverse Events

    12 months

  • Composite Arrhythmia Burden

    12 months

Study Arms (2)

Radiofrequency Ablation

ACTIVE COMPARATOR

Radiofrequency ablation (RFA) will be performed after 3-month observation period. EPS and RFA will be performed using standard techniques and protocols similar to those patients that do not participate in this clinical study. In the event of polymorphic PVCs, all morphologies are to be targeted for ablation

Procedure: Radiofrequency ablation

Antiarrhythmic Drug

ACTIVE COMPARATOR

Antiarrhythmic drugs (AADs) will be only initiated after 3-month observation period. AAD therapy of choice is amiodarone. Amiodarone loading dose of 10 grams is recommended, followed by maintenance dose of 200-400mg daily to achieve successful PVC suppression. Investigators define successful PVC suppression only if ≥ 80% absolute reduction in PVC burden is achieved after a drug or intervention. Alternatively, sotalol and/or propafenone could be considered at discretion of electrophysiologists (sotalol dose of at least 120mg twice daily, propafenone 150-300mg tid) if there is a significant concern of safety profile of amiodarone.

Drug: Amiodarone (Antiarrhythmic drug)

Interventions

RFA to achieve PVC suppression will be performed using standard techniques and protocols similar to those patients that do not participate in this clinical study.

Also known as: Ablation
Radiofrequency Ablation

AAD therapy of choice is amiodarone. Amiodarone loading dose of 10 grams is recommended, followed by maintenance dose of 200-400mg daily to achieve successful PVC suppression. Alternatively, sotalol and/or propafenone could be considered at discretion of electrophysiologists (sotalol dose of at least 120mg twice daily, propafenone 150-300mg tid) if there is a significant concern of safety profile of amiodarone.

Also known as: Amiodarone
Antiarrhythmic Drug

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • LV dysfunction (calculated LVEF \< or equal to45% based on Echo) within 150 days of Enrollment (Day 0)
  • PVC burden \> or equal to 10% by at least a 24-hr ambulatory Holter monitor (within 150 days of Enrollment (Day 0)

You may not qualify if:

  • Age \< 18 years old
  • Current amiodarone use or within last 2 months
  • Current use of antiarrhythmic drugs class I or III
  • Contraindication to amiodarone use or any other class III antiarrhythmic
  • Severely symptomatic PVCs (unable to complete 3-month observation period)
  • Severe/significant CAD with planned revascularization in the near future
  • Complete AV block and pacemaker dependent
  • Pacemaker or ICD with \>10% RV pacing
  • Severe valvular heart disease or planned valvular/cardiac surgery
  • Uncontrolled / untreated endocrinopathies
  • Uncontrolled HTN, (systolic BP \>180mmHg or diastolic \>110 mmHg)
  • Hypertrophic cardiomyopathy
  • Systemic infiltrative and immune disorders
  • Family history of dilated CM in a first degree relative
  • Alcohol abuse or illicit drug use
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

University of California Los Angeles Medical Center

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

James A. Haley Veterans' Hospital

Tampa, Florida, 33612, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Roxbury VA Medical Center

West Roxbury, Massachusetts, 02132, United States

Location

Northwell Health System-Staten Island University Hospital

Staten Island, New York, 10305, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Libin Cardiovascular Institute, University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

Related Publications (1)

  • Torrado J, Sima A, Comstuck C, Kaszala K, Tan A, Koneru J, Frankel DS, Marchlinski F, Kowalski M, Sharma P, Gerstenfeld EP, Vaseghi M, Shivkumar K, Malhotra R, Morillo C, Ellenbogen KA, Huizar JF. Prevalence of frequent premature ventricular contractions and left-ventricular systolic dysfunction in patients receiving Holter monitoring. J Cardiovasc Electrophysiol. 2025 Jan;36(1):54-61. doi: 10.1111/jce.16478. Epub 2024 Oct 24.

MeSH Terms

Conditions

Ventricular Premature ComplexesCardiomyopathies

Interventions

Radiofrequency AblationAmiodaroneAnti-Arrhythmia Agents

Condition Hierarchy (Ancestors)

Cardiac Complexes, PrematureArrhythmias, CardiacHeart DiseasesCardiovascular DiseasesCardiac Conduction System DiseasePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiofrequency TherapyTherapeuticsAblation TechniquesSurgical Procedures, OperativeBenzofuransHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsCardiovascular AgentsTherapeutic UsesPharmacologic ActionsChemical Actions and Uses

Study Officials

  • Jose F Huizar, M.D.

    McGuire VA Medical Center

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: PVC suppression with either antiarrhythmic drugs or radiofrequency ablation
Sponsor Type
FED
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Arrhythmia and Device Clinic

Study Record Dates

First Submitted

July 18, 2017

First Posted

July 25, 2017

Study Start

August 1, 2018

Primary Completion

August 31, 2021

Study Completion

August 31, 2021

Last Updated

April 14, 2021

Record last verified: 2021-04

Data Sharing

IPD Sharing
Will share

This is solely a pilot study of frequent PVCs and cardiomyopathy. Results of this preliminary data will not provide final definitive data, yet investigators will make it available. However, investigators will make clear that this pilot data is not intended to answer benefits of different PVC suppression strategies to avoid misinterpretation or inaccurate conclusions based solely on preliminary data.

Shared Documents
CSR
Time Frame
3-6 months after pilot study has been completed

Locations