Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03228823 |
| Other study ID # |
NIH ID 9372611 |
| Secondary ID |
R34HL138110-01 |
| Status |
Active, not recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2018 |
| Est. completion date |
August 31, 2021 |
Study information
| Verified date |
April 2021 |
| Source |
Hunter Holmes Mcguire Veteran Affairs Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
