Prophylactic Frequent Premature Ventricular complexeS sUPPression on Left ventriculaR Function impairmEnt in aSymptomatic patientS (SUPPRESS)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Ventricular Dysfunction, Left; Premature Ventricular Contractions
• Intervention / Treatment: Drug: Experimental group; Drug: Control group

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.

• Study Type: Interventional
• Enrollment (Estimated): 298
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; 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).	Drug: Experimental group; medical treatment including drug administration ± catheter ablation (Ablation can be performed if the PVC burden remain >10% after 2 lines of AAD treatment).; Other Names: medical treatment
Active Comparator: Control group; Patients with therapeutic abstention or no treatment modification such as drug therapy/ Therapeutic abstention or no modification of therapy	Drug: Control group; patients of this group have no therapeutic or no treatment modification such as drug therapy; Other Names: Therapeutic abstention or no modification of therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
occurence of Left ventricular dysfunction (PVC-iCMP)	The primary endpoint will be the development of left ventricular 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).	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Death	Death from any cause	24 months
Rate of Cardiovascular Death	measure of safety endpoint: Death cause of death	24 months
Rate of Hospitalization for an adverse event	occurence of adverse events (AE) and serious adverse events (SAE) within follow-up that may be linked or not to anti-arrhythmic drugs (AAD) or ablation procedure	24 months
Percentage of patients with a PVC burden <10%	measure of efficacy endpoints: PVC burden will be measured the second year following randomization	during 24 months follow up
LVEF variation	LVEF variation(from baseline to M24)	24 months
Nt-ProBNP relative variation	Nt-ProBNP relative variation from baseline to M24	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 24, 2023

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Cardiac Complexes, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Ventricular Dysfunction; Ventricular Dysfunction, Left; Ventricular Premature Complexes
• Other Study ID Numbers: APHP180618

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No