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

Endocarditis Clinical Trial

— CHIRURGENDO  

Official title:

Early Valve Surgery Versus Conventional Treatment in Infective Endocarditis Patients With High Risk of Embolism: a Randomized Superiority Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03718052
• Other study ID #: P160952J
• Status: Recruiting
• Phase: N/A
• Start date: April 11, 2019
• Est. completion date: April 11, 2026

Study information

• Verified date: June 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Xavier DUVAL
• Phone: 140257135
• Email: xavier.duval[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 208
• Est. completion date: April 11, 2026
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Embolism
• Endocarditis
• Endocarditis, Bacterial

Intervention

Procedure:
• Early valve surgery (EVS)
Early valve surgery (EVS) within 72 hours of randomization
• Conventional Care
Conventional care according to the 2015 European guidelines.

Locations

Country	Name	City	State
France	Bichat Claude Bernard Hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

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