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

Not Applicable

Recruiting

• Conditions: Endocarditis
• Interventions: Procedure: Early valve surgery (EVS); Procedure: Conventional Care

• Registration Number: NCT03718052
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2018-10-10
• Study First Submitted QC: 2018-10-22
• Study First Posted: 2018-10-24
• Study Start: 2019-04-11
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-05
• Last Update Posted: 2024-06-07
• Primary Completion: 2025-05-30
• Study Completion: 2026-04-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 208

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early valve surgery (EVS)	Early valve surgery (EVS)	Cardiac surgery as soon as possible within 72 hours of randomization
Conventional care	Conventional Care	Conventional care according to the 2015 European guidelines.

Primary Outcome Measures

Name	Time	Method
Complications and deaths in all included patient	Week 6	A composite of all-cause death and clinically symptomatic embolic events within 6 weeks from randomization in all included patient.

Secondary Outcome Measures

Name	Time	Method
Complications and deaths in patient with definite IE	Week 6	All-cause death and clinically symptomatic embolic events from randomization in patient with definite IE
Complications and deaths	Months 6 and 12	Combination of all-cause death and clinically symptomatic embolic events documented by imaging studies up to 6 months and one-year after randomization.
Intensive care scale	Week 6 , Months 3, 6 and 12	Glasgow outcome scale and Rankin scale at week 6, month 3, 6 and one-year visits.
Infective EI relapse	Months 6 and 12	Relapse of infective IE up to 6 months and one-year after randomization.
Infective EI recurrences	Months 6 and 12	Recurrences of infective IE up to 6 months and one-year after randomization.
Rehospitalization	Week 6, Months 6 and 12	Readmission due to development of congestive heart failure up to 6 weeks, 6 months and one-year after randomization
Deaths	Months 6 and 12	All-cause death up to 6 months and one-year (post study analysis) after randomization
Symptomatic embolic events	Months 6 and 12	All clinically symptomatic embolic events documented by imaging studies up to 6 months and one-year after randomization
Rehospitalization for valve surgery	Months 6 and 12	Readmission for valve surgery (between hospital discharge and 6 months and one-year after enrolment) in patients operated on during the acute phase of IE
Quality of life scale 1	Months 6 and 12	WhoQol scale up to 6 months and one-year after randomization.
Quality of life scale 2	Months 6 and 12	SF36 up to 6 months and one-year after randomization.
Delay between randomization and surgery	Months 12	Time interval between randomization and date of cardiac surgery in patients operated-on during the acute phase of the IE.
Thrombosis and ischemia	Months 6 and 12	Six month and one-year prosthesis thrombosis, severe adverse events due to anticoagulation, ischemic stroke due to documented suboptimal anticoagulation

Trial Locations

Locations (1)

Bichat Claude Bernard Hospital; 🇫🇷 Paris, France