Clinical trial NCT03228823: Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
Official title: Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS): A Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ventricular Premature Beats, Contractions, or Systoles
Cardiomyopathies
Keywords: Premature Ventricular contractions
Cardiomyopathy
Lead sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
Sponsor class: FED
Collaborators: name: Virginia Commonwealth University
name: University of California, San Francisco
name: University of Calgary
name: Washington University School of Medicine
name: Wake Forest University Health Sciences
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-07-25
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PVC suppression with either antiarrhythmic drugs or radiofrequency ablation
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Improvement of left ventricular ejection fraction after PVC suppression
timeFrame: 12 months
measure: Responders to PVC suppression strategy
timeFrame: 12 months
Secondary outcomes:
measure: Successful PVC suppression
timeFrame: 12 months
measure: Composite Adverse Events
timeFrame: 12 months
measure: Composite Arrhythmia Burden
timeFrame: 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Tampa
country: United States
facility: James A. Haley Veterans' Hospital
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: West Roxbury
country: United States
facility: Roxbury VA Medical Center
state: Massachusetts
city: Staten Island
country: United States
facility: Northwell Health System-Staten Island University Hospital
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Calgary
country: Canada
facility: Libin Cardiovascular Institute, University of Calgary
state: Alberta
Study officials:
affiliation: McGuire VA Medical Center
name: Jose F Huizar, M.D.
role: STUDY_DIRECTOR
References: