Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Edward Gerstenfeld, M.D.Teresa DeMarco, M.D.

Description

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.

Official Title

Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS): A Pilot Study

Details

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.

Keywords

Ventricular Premature Beats, Contractions, or Systoles Cardiomyopathies Premature Ventricular contractions Cardiomyopathy Premature Birth Ventricular Premature Complexes Cardiac Complexes, Premature Amiodarone Propafenone Anti-Arrhythmia Agents Radiofrequency ablation Amiodarone (Antiarrhythmic drug) Antiarrhythmic Drug

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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 CAN'T join 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
  • 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

Locations

  • University of California, San Francisco accepting new patients
    San Francisco California 94143 United States
  • University of California Los Angeles Medical Center accepting new patients
    Los Angeles California 90095 United States

Lead Scientists

  • Edward Gerstenfeld, M.D.
    Dr Gerstenfeld is the Melvin Scheinman Endowed Professor of Medicine and Chief of the Section of Cardiac Electrophysiology at UCSF.
  • Teresa DeMarco, M.D.
    CLINICAL INTERESTS: Advanced heart failure, cardiomyopathies, heart transplantation, mechanical circulatory support, and pulmonary hypertension RESEARCH INTERESTS: Translational research in the diagnosis, prognosis, medical and surgical treatment for the above disease states

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Hunter Holmes Mcguire Veteran Affairs Medical Center
ID
NCT03228823
Phase
Phase 4
Study Type
Interventional
Last Updated