Clinical trial NCT05784051: Prophylactic Frequent Premature Ventricular complexeS sUPPression on Left ventriculaR Function impairmEnt in aSymptomatic patientS
Official title: Prophylactic Frequent Premature Ventricular complexeS sUPPression on Left ventriculaR Function impairmEnt in aSymptomatic patientS
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Premature Ventricular Contractions
Ventricular Dysfunction, Left
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-03-24
Enrollment: 298
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The SUPPRESS study will be a national multicenter randomized open label trial using the PROBE study design (Prospective Randomized Open Blinded End-point).

Patients fulfilling the inclusion criteria (asymptomatic patients with frequent (\> 10%/day) PVCs and normal LVEF) and without any exclusion criteria that agree to enter the protocol will be randomized to:

1. Experimental group: 149 patients treated for PVCs with drug therapy and/or catheter ablation/ medical treatment including drug administration ± catheter ablation (Ablation can be performed if the PVC burden remain \>10% after 2 lines of AAD treatment).
2. Control group: 149 patients with therapeutic abstention or no treatment modification such as drug therapy/ Therapeutic abstention or no modification of therapy
Primary purpose: PREVENTION

Brief summary: The main objective of the study is to demonstrate that prophylactic treatment of patients with asymptomatic frequent (\>10%) PVCs is superior to simple follow-up strategy with no therapy to prevent subsequent LV dysfunction at 24 months. The prophylactic treatment is based on drugs ± ablation (ablation can be performed if the PVC burden remain \>10% after 2 lines of AAD treatment since the initiation of the study).

The primary endpoint will be the development of LV dysfunction (PVC-iCMP) defined as a 15% relative LVEF decrease (and/or a LVEF \<50%) within 2 years following randomization, on cardiac magnetic resonance imaging (cMRI) (or transthoracic echocardiography (TTE) when not possible).

Detailed description: Premature ventricular contractions (PVCs) are frequently encountered in clinical practice, in the setting of underlying heart disease as well as in "normal" hearts. Frequent PVCs have been shown to impact long term prognosis in patients with structurally normal hearts,\[1\] as well as in documented cardiomyopathy. In both settings, PVCs may cause symptoms and, in rare cases, sudden cardiac death. For about two decades, it has been accepted that frequent PVCs may also induce left ventricular (LV) dysfunction called PVC-induced cardiomyopathy (PVC-iCMP). Indeed, PVC suppression by using drugs or catheter ablation has been associated with full recovery of left ventricular dysfunction.\[2-4\] De facto, PVC-iCMP diagnosis as well as identification of predictors has always been established retrospectively. Therefore, risk stratification or simply knowing the exact incidence of the disease in exposed patients remain difficult.

European and US guidelines recommend to treat symptomatic PVC patients regardless of the burden or their risk profile, as well as "frequent PVCs" associated with LV dysfunction (Experts tend to consider worthwhile treating for burden \>10%, which was the lowest burden associated with PVC-iCMP).

However, there is no clear recommendation for asymptomatic patients exposed to very frequent PVCs, at risk of developing cardiomyopathy. As no previous studies included such population, expert suggested that these patients should be at least closely followed. Consequently, management of such patients is widely heterogeneous.

The hypothesis of this study is that prophylactic suppression of very frequent PVCs (\>10%) will prevent or significantly reduce the incidence of PVC-iCMP.

Eligibility criteria: Inclusion Criteria:

Inclusion criteria (all must be present):

1. 18 ≤ Age ≤ 85
2. PVC burden ≥ to 10% regardless of current or preexisting antiarrhythmic drug intake (for instance, a patient under betablocker therapy because of his PVCs or hypertension can be included)
3. Asymptomatic status
4. Normal (\>or= 55%) LVEF. Patients with underlying cardiomyopathy can be included as long as LV function remains preserved.
5. Signed informed consent

Exclusion criteria (any of them):

1. Pregnant woman or Female of childbearing potential without effective method of birth control or nursing woman.
2. Patients that can't undergo MRI study
3. De novo requirement for antiarrhythmic drug prescription for another indication (e.g. atrial fibrillation...)
4. The physician already decided that the patient requires drug initiation or escalation;
5. Ischemic cardiomyopathy requiring revascularization (PCI or surgery)
6. History of LV dysfunction
7. Participation in another research involving the human person
8. Patient under legal protection
9. Non affiliation to a social security scheme

Primary outcomes:
measure: occurence of Left ventricular dysfunction (PVC-iCMP)
timeFrame: 24 months
Secondary outcomes:
measure: Rate of Death
timeFrame: 24 months
measure: Rate of Cardiovascular Death
timeFrame: 24 months
measure: Rate of Hospitalization for an adverse event
timeFrame: 24 months
measure: Percentage of patients with a PVC burden <10%
timeFrame: during 24 months follow up
measure: LVEF variation
timeFrame: 24 months
measure: Nt-ProBNP relative variation
timeFrame: 24 months
Other outcomes:
Locations:
Study officials:
References: