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Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS) (PAPS)

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ClinicalTrials.gov Identifier: NCT03228823
Recruitment Status : Recruiting
First Posted : July 25, 2017
Last Update Posted : June 12, 2019
Sponsor:
Collaborators:
Virginia Commonwealth University
University of California, San Francisco
University of Calgary
Washington University School of Medicine
Wake Forest University Health Sciences
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Jose Huizar, Hunter Holmes Mcguire Veteran Affairs Medical Center

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.


Condition or disease Intervention/treatment Phase
Ventricular Premature Beats, Contractions, or Systoles Cardiomyopathies Procedure: Radiofrequency ablation Drug: Amiodarone (Antiarrhythmic drug) Phase 4

Detailed Description:

Rationale. Frequent PVCs have shown to induce a reversible cardiomyopathy (PVC-CM). Yet, it is unclear why some patients develop PVC-CM, while others do not. Appropriate diagnosis and treatment of patients with PVC-CM is believed to carry significant benefits, improving quality of life (QOL), HF symptoms / admissions and life expectancy. Currently, these patients are offered radiofrequency ablation (RFA), antiarrhythmic drugs (AADs) or no treatment depending on physician's experience and resources. Nevertheless, no randomized-prospective study exists to support the benefit of RFA. Thus, a large-scale multicenter randomized clinical trial entitled "Prospective Assessment of PVC Suppression in Cardiomyopathy (PAPS)"' study has been planned to compare these treatment strategies. However, a PAPS pilot study is proposed to better estimate the potential affected patient population, limitations of enrollment, rate of clinical outcomes, potential crossover and drop out. This pilot study is key to better design and power the large-scale multicenter PAPS trial.

Objective. PAPS pilot study is a randomized clinical trial to assess the feasibility of enrolling, randomizing treatment strategies and retaining participants with frequent PVCs and associated CM.

Hypotheses. Our main hypotheses of the PAPS pilot study are:

  1. A large-scale randomized PAPS clinical study is feasible with minimal barriers of enrollment, treatment crossover and drop out due to a unique design including a short observation period and PVC suppression strategy in all participants.
  2. The rate of responders (defined as improvement of LVEF ≥ 10% points) with HF medical therapy alone during observation period will be less than 15%. In contrast, RFA and AADs will have a responder rate of at least 35% in the same population. Furthermore, RFA will have a greater 1-year response rate when compared to AAD therapy.
  3. RFA will have a lower rate of composite adverse events (worsening NYHA class, HF admission, treatment side effects & complications, and death), arrhythmia burden and a better long-term tolerance than AADs.

Methods. A prospective clinical pilot study is planned to prove the feasibility of a large-scale multicenter clinical trial (PAPS study) of patients with probable PVC-CM. This 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, all patients will undergo a baseline cardiac MR if clinically indicated and be allowed a 3-month observation period (optimal HF medical therapy). To assess the effects of PVC suppression, changes in LV function, rate of responders (defined above), PVC burden/arrhythmias and clinical/functional status (QOL, HF symptoms and admissions, NYHA class) and adverse events will be compared between observation period and both PVC suppression strategies (RFA or AAD). To identify the best PVC suppression strategy, similar comparisons between RFA and AAD treatment groups will be performed at 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 summary, the multicenter PAPS pilot study is intended to better estimate the prevalence of PVC-CM, prove feasibility and rates of clinical outcomes. This pilot study with a multidisciplinary approach will pave the way for a large-scale randomized PAPS trial to identify the best treatment strategy for patients with PVC-CM. Treating and reversing PVC-CM with its associated HF morbidity and mortality will impact not only healthcare spending, but most importantly it will improve patient's health, quality of life and long-term prognosis.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: PVC suppression with either antiarrhythmic drugs or radiofrequency ablation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS): A Pilot Study
Actual Study Start Date : August 1, 2018
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cardiomyopathy

Arm Intervention/treatment
Active Comparator: Radiofrequency Ablation
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
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.
Other Name: Ablation

Active Comparator: Antiarrhythmic Drug
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)
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.
Other Name: Amiodarone




Primary Outcome Measures :
  1. Improvement of left ventricular ejection fraction after PVC suppression [ Time Frame: 12 months ]
    Compare the overall improvement or change in LVEF between RFA and AAD groups.

  2. Responders to PVC suppression strategy [ Time Frame: 12 months ]
    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.


Secondary Outcome Measures :
  1. Successful PVC suppression [ Time Frame: 12 months ]
    Efficacy of Radiofrequency ablation vs. Antiarrhythmic drugs to achieve successful PVC suppression (defined as a reduction of PVC burden greater than ≥80%).

  2. Composite Adverse Events [ Time Frame: 12 months ]
    Composite end-point of adverse events, including worsening in NYHA functional class (I-IV), number of HF and cardiac-related admissions, RFA complications and AAD adverse effects and cardiovascular death.

  3. Composite Arrhythmia Burden [ Time Frame: 12 months ]
    Composite end-point of arrhythmia burden, including PVC recurrence, non-sustained (< 30sec) and sustained (> 30sec) ventricular arrhythmias and arrhythmic sudden cardiac death



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • Contraindication to short-term acute anticoagulation (due to possible randomization to ablation)
  • Atrial fibrillation and flutter with rapid ventricular response with possible tachycardia-induced cardiomyopathy
  • Possible infectious etiology of cardiomyopathy
  • Pregnant or lactating women
  • Previous PVC ablation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03228823


Contacts
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Contact: Jose F Huizar, M.D. 804-675-5466 jose.huizar2@va.gov
Contact: Pamela K Summers, BS, CCRP 804-675-6831 pamela.summers@va.gov

Locations
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United States, California
University of California Los Angeles Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Julie Sorg, R.N., M.S.N.         
Contact: Marmar Vaseghi, M.D., Ph.D.    310 206 2235    mvaseghi@mednet.ucla.edu   
Principal Investigator: Marmar Vaseghi, M.D., Ph.D.         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Sara Yogi, B.A.    415-502-3803    sara.yogi@ucsf.edu   
Contact: Edward Gerstenfeld, M.D.    415-476-5706    edward.gerstenfeld@ucsf.edu   
Principal Investigator: Edward Gerstenfeld, M.D.         
Principal Investigator: Teresa DeMarco, M.D.         
United States, Florida
James A. Haley Veterans' Hospital Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Visola Alimova    813-972-2000 ext 5293    visola.alimova@va.gov   
Principal Investigator: Raymond Cutro, MD         
Sub-Investigator: Fabio Leonelli, MD         
Sub-Investigator: David Wilson, MD         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Kelli Jones, R.N.    312-942-8707    kelli_jones@rush.edu   
Contact: Parikshit Sharma, M.D.    312-942-8707    parikshit_s_sharma@rush.edu   
Principal Investigator: Parikshit Sharma, M.D.         
United States, Massachusetts
Roxbury VA Medical Center Not yet recruiting
West Roxbury, Massachusetts, United States, 02132
Contact: Adelqui Peralta, M.D.    857-203-6841    adelqui.peralta@va.gov   
Principal Investigator: Adelqui Peralta, M.D.         
United States, New York
Northwell Health System-Staten Island University Hospital Recruiting
Staten Island, New York, United States, 10305
Contact: Richard Dima    718-226-1489    rdima@northwell.edu   
Contact: Marcin Kowalski, M.D.    718-226-4645    mkowalski1@northwell.edu   
Principal Investigator: Marcin Kowalski, M.D.         
United States, Pennsylvania
University of Pennsylvania Medical Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Mary Gnap, R.N.    215-349-8446    mary.gnap@uphs.upenn.edu   
Contact: David Frankel, M.D.    215-662-6801    david.frankel@uphs.upenn.edu   
Principal Investigator: David Frankel, M.D.         
United States, Virginia
McGuire VA Medical Center Recruiting
Richmond, Virginia, United States, 23249
Contact: Pamela K Summers, B.S., CCRP    804-675-5000 ext 6831    pamela.summers@va.gov   
Contact: Donna Sargent, R.N., BSN    804-675-5466    donna.sargent@va.gov   
Principal Investigator: Jose F Huizar, M.D.         
Sub-Investigator: Karoly Kaszala, M.D., Ph.D.         
Sub-Investigator: Alex Y Tan, M.D.         
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Kenneth A Ellenbogen, M.D.    804-628-0147    kenneth.Ellenbogen@vcuhealth.org   
Contact: Melissa Hockman, R.N., B.S.N.    (804) 675-5167    melissa.hockman@vcuhealth.org   
Principal Investigator: Kenneth A Ellenbogen, M.D.         
Principal Investigator: Adam Sima, Ph.D.         
Canada, Alberta
Libin Cardiovascular Institute, University of Calgary Not yet recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Jennifer McKeage, R.N.    403-210-6047    jmckeage@ucalgary.ca   
Contact: Carlos A. Morillo, M.D.    403-944-2670    carlos.morillo@ucalgary.ca   
Principal Investigator: Carlos A Morillo, M.D.         
Sponsors and Collaborators
Hunter Holmes Mcguire Veteran Affairs Medical Center
Virginia Commonwealth University
University of California, San Francisco
University of Calgary
Washington University School of Medicine
Wake Forest University Health Sciences
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Study Director: Jose F Huizar, M.D. McGuire VA Medical Center
  Study Documents (Full-Text)

Documents provided by Jose Huizar, Hunter Holmes Mcguire Veteran Affairs Medical Center:
Informed Consent Form  [PDF] June 28, 2017


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Responsible Party: Jose Huizar, Director, Arrhythmia and Device Clinic, Hunter Holmes Mcguire Veteran Affairs Medical Center
ClinicalTrials.gov Identifier: NCT03228823     History of Changes
Other Study ID Numbers: NIH ID 9372611
R34HL138110-01 ( U.S. NIH Grant/Contract )
First Posted: July 25, 2017    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Clinical Study Report (CSR)
Time Frame: 3-6 months after pilot study has been completed

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Jose Huizar, Hunter Holmes Mcguire Veteran Affairs Medical Center:
Premature Ventricular contractions
Cardiomyopathy
Additional relevant MeSH terms:
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Premature Birth
Cardiomyopathies
Ventricular Premature Complexes
Cardiac Complexes, Premature
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Heart Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Cardiac Conduction System Disease
Pathologic Processes
Amiodarone
Propafenone
Anti-Arrhythmia Agents
Vasodilator Agents
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Sodium Channel Blockers
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 CYP3A Inhibitors
Voltage-Gated Sodium Channel Blockers