Early Valve Surgery Versus Conventional Treatment in Infective Endocarditis Patients With High Risk of Embolism

NCT ID: NCT03718052

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-11
• Study Completion Date: 2026-07-31

Brief Summary

Infective endocarditis (IE) is associated with an overall in-hospital mortality rate of 15-25% and a high incidence of embolic events (20-50%). Leading causes of mortality are heart failure (HF) resulting from valve dysfunction, and stroke caused by vegetation embolization. The rate of symptomatic embolic events occurring after antibiotic initiation is around 15%. Valve surgery benefit has been clearly demonstrated in patients with periannular complications and moderate to severe HF resulting from acute valve regurgitation. The timing of surgery to prevent embolism is critical since the risk of new embolic event is highest during the first weeks of antibiotic treatment.

The primary objective is to compare clinical outcomes of Early Valve Surgery (as soon as possible within 72 hours of randomization) with those of a conventional management based on current guidelines in patients with native left-sided IE and high risk of embolism.

208 patients (104 patients per arm) will be included in a national multicenter (21 centers) prospective randomized open blinded end-point (PROBE) sequential superiority trial.

Detailed Description

Infective endocarditis (IE) is associated with an overall in-hospital mortality rate of 15-25% and a high incidence of embolic events (20-50%). Leading causes of mortality are heart failure (HF) resulting from valve dysfunction, and stroke caused by vegetation embolization. The rate of symptomatic embolic events occurring after antibiotic initiation is around 15%. Valve surgery benefit has been clearly demonstrated in patients with periannular complications and moderate to severe HF resulting from acute valve regurgitation. Indications of valve surgery for prevention of embolic complications are less clearly defined. Potential complications of valve surgery and of implanted permanent prosthetic valve are to be balanced against their potential benefits in terms of prevented embolism and improved survival. The timing of surgery to prevent embolism is critical since the risk of new embolic event is highest during the first weeks of antibiotic treatment. The points in favor of early valve surgery (EVS) in patients with high embolic risk include the following 1) patients with high risk of embolism are identified by transesophageal echocardiography (TOE); 2) advances in surgical management of IE dramatically lowered postoperative mortality; 3) 2015 European ESC IE guidelines state that valve surgery should be performed in IE with vegetation above 10 mm AND an embolic event occurring while patients are receiving antibiotic (grade I/B) and should be considered in IE with vegetation above 30 mm (Grade IIaB ) and may be above 10 mm and severe valve regurgitation.

The primary objective is to compare clinical outcomes of EVS (as soon as possible within 72 hours of randomization) with those of a conventional management based on current 2015 European ESC guidelines in patients with native left-sided IE and high risk of embolism.

The primary assessment criterion is a composite of all-cause death and clinically symptomatic embolic events within 6 weeks from randomization in all included patient.

208 patients (104 patients per arm) will be included in a national multicenter (21 centers) prospective randomized open blinded end-point (PROBE) sequential superiority trial.

Conditions

Endocarditis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Early valve surgery (EVS)

Cardiac surgery as soon as possible within 72 hours of randomization

Group Type: EXPERIMENTAL

Early valve surgery (EVS)

Intervention Type: PROCEDURE

Early valve surgery (EVS) within 72 hours of randomization

Conventional care

Conventional care according to the 2015 European guidelines.

Group Type: ACTIVE_COMPARATOR

Conventional Care

Intervention Type: PROCEDURE

Conventional care according to the 2015 European guidelines.

Interventions

Early valve surgery (EVS)

Early valve surgery (EVS) within 72 hours of randomization

Intervention Type: PROCEDURE

Conventional Care

Conventional care according to the 2015 European guidelines.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Definite or possible IE based on the modified Duke criteria (ESC 2015)

3. Length of vegetation on native aortic and/or mitral valve, as assessed by TOE * :

• between 10 and 15 mm AND (severe regurgitation OR previous symptomatic or asymptomatic embolic events)
• OR above or equal to 15 mm

4. Initiation of specific IE active antibiotic less than 5 days (≤120 hours) before inclusion

5. For non-menopause women: negative blood or urinary β-HCG test. *If the patient has several vegetations, only one vegetation with these criterions, is enough to included patient.

Exclusion Criteria

1. Patient with "emergent" indication of surgery based on 2015 European Guidelines

2. Prosthetic valve endocarditis

3. Patient who is not candidate for surgery due to high risk post-surgery mortality including for example coexisting major embolic stroke with a high risk of hemorrhagic transformation, symptomatic hemorrhagic stroke; poor medical status, such as coexisting malignancies…

4. No written informed consent from the patient or a legal representative if appropriate

5. Patient with no national health or universal plan affiliation coverage

6. Pregnancy

7. Patient under guardianship or curatorship

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xavier Duval

Role: PRINCIPAL_INVESTIGATOR

Bichat Hospital

Locations

Bichat Claude Bernard Hospital

Paris, , France

Countries

France

Other Identifiers

P160952J

Identifier Type: -

Identifier Source: org_study_id