Clinical trial NCT03718052: Early Valve Surgery Versus Conventional Treatment in Infective Endocarditis Patients With High Risk of Embolism
Official title: Early Valve Surgery Versus Conventional Treatment in Infective Endocarditis Patients With High Risk of Embolism: a Randomized Superiority Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Endocarditis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-10-24
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Complications and deaths in all included patient
timeFrame: Week 6
Secondary outcomes:
measure: Complications and deaths in patient with definite IE
timeFrame: Week 6
measure: Complications and deaths
timeFrame: Months 6 and 12
measure: Deaths
timeFrame: Months 6 and 12
measure: Symptomatic embolic events
timeFrame: Months 6 and 12
measure: Intensive care scale
timeFrame: Week 6 , Months 3, 6 and 12
measure: Infective EI relapse
timeFrame: Months 6 and 12
measure: Infective EI recurrences
timeFrame: Months 6 and 12
measure: Rehospitalization
timeFrame: Week 6, Months 6 and 12
measure: Rehospitalization for valve surgery
timeFrame: Months 6 and 12
measure: Thrombosis and ischemia
timeFrame: Months 6 and 12
measure: Quality of life scale 1
timeFrame: Months 6 and 12
measure: Quality of life scale 2
timeFrame: Months 6 and 12
measure: Delay between randomization and surgery
timeFrame: Months 12
Other outcomes:
Locations:
city: Paris
country: France
facility: Bichat Claude Bernard Hospital
Study officials:
affiliation: Bichat Hospital
name: Xavier Duval
role: PRINCIPAL_INVESTIGATOR
References: