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

Ventricular Dysfunction, Left Clinical Trial

— SUPPRESS  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05784051
• Other study ID #: APHP180618
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: October 1, 2023
• Est. completion date: June 1, 2027

Study information

• Verified date: September 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 298
• Est. completion date: June 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Premature Birth
• Premature Ventricular Contractions
• Ventricular Dysfunction
• Ventricular Dysfunction, Left
• Ventricular Premature Complexes

Intervention

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).
• Control group
patients of this group have no therapeutic or no treatment modification such as drug therapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Rate of Death	Death from any cause	24 months
Secondary	Rate of Cardiovascular Death	measure of safety endpoint: Death cause of death	24 months
Secondary	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
Secondary	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
Secondary	LVEF variation	LVEF variation(from baseline to M24)	24 months
Secondary	Nt-ProBNP relative variation	Nt-ProBNP relative variation from baseline to M24	24 months