Endocarditis
Conditions
Keywords
Endocarditis
Brief summary
There have been no prospective clinical studies in infective endocarditis comparing early surgery with the conventional treatment strategy based on current guidelines. The purpose of this prospective randomized trial is to compare clinical outcomes of early surgery versus conventional treatment strategy in patients with high embolic risk of infective endocarditis.
Detailed description
Infective Endocarditis is still associated with high mortality (16-25%) and high incidence of embolic events (10-49%), and the optimal therapeutic strategy remains unclear. The benefit of surgery was particularly high in patients with abscess formation, periannular complications, and moderate to severe heart failure related to acute mitral or aortic regurgitation. Retrospective studies reported that valve surgery was associated with improved survival, but the benefit of early surgery has not been adequately studied due to inherent treatment biases and significant differences in baseline characteristics. Embolic indications for surgery are more controversial, and surgery is usually performed in cases of recurrent emboli and persist vegetations despite appropriate antibiotic treatment. The combined risk of early surgery and valve prosthesis needs to be balanced against the potential benefit of preventing embolism and improving survival. Risk-benefit balance changes recently to favor early surgery in patients with high embolic risk of endocarditis for the following reasons. Identification of patients with high risk of embolism becomes possible with the use of transesophageal echocardiography. Patients with vegetation length \> 10 mm on transesophageal echocardiography have a significantly higher risk of embolization. With advances in surgical technique, urgent surgery is feasible with low operative mortality, and the success rate of valve repair has been increased. To the best of our knowledge, there have been no prospective outcome studies comparing early surgery with the conventional treatment strategy based on current guidelines. The purpose of this multi-center, prospective, randomized trial is to compare clinical outcomes of early surgery versus conventional treatment strategy in patients with high embolic risks of infective endocarditis.
Interventions
PROCEDUREValve surgery with removal of vegetations
Early valve repair or replacement with removal of vegetations within 48 hours of randomization
Sponsors
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed as infective endocarditis based on modified Duke criteria fulfilling both conditions: * severe mitral or aortic regurgitation * vegetation length \> 10 mm on mitral or aortic valve
Exclusion criteria
* Patients with urgent and emergent indication of surgery based on current guidelines; aortic abscess, moderate to severe heart failure due to valvular regurgitation, periannular complications, fungal endocarditis * Prosthetic valve endocarditis * Patient without vegetations on echocardiography * Patients with ischemic or hemorrhagic stroke within 2 weeks before the admission * Patients referred from other hospitals more than 7 days after the appropriate antibiotic treatment of infective endocarditis * Patients who were not candidates for surgery based on age \> 80 years and coexisting malignancies * Patients who did not consent to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With In-hospital Death or Clinical Embolic Events | within 6 weeks from the randomization | The composite of in-hospital death and clinical embolic events confirmed by imaging studies: the acute onset of clinical symptoms or signs of embolism and the occurrences of new lesions, as confirmed by follow-up imaging studies. |
Secondary
| Measure | Time frame |
|---|---|
| All-cause Death | up to 6 month after enrollment |
| Recurrences of Infective Endocarditis | up to 6 months after enrollment |
| All Embolic Events Including Symptomatic and Asymptomatic Embolization Documented by Imaging Studies | up to 6 months after enrollment |
| Readmission Due to Development of Congestive Heart Failure | up to 6 months after enrollment |
Countries
South Korea
Participant flow
Recruitment details
Patients were eligible for enrollment if they were diagnosed as definite infective endocarditis and had both severe mitral or aortic valve disease and vegetation length \> 10 mm. Between September 2006 and March 2011, a total of 76 patients were enrolled at the Asan Medical Center (n=71) and Seoul National University Hospital (n=5) in Korea.
Pre-assignment details
The exclusion criteria were defined as patients with moderate to severe CHF; heart block; annular or aortic abscess; fungal endocarditis; and those who were not candidates for early surgery on the basis of age \> 80 years, coexisting major embolic stroke with a risk of hemorrhagic transformation and/or poor medical status.
Participants by arm
| Arm | Count |
|---|---|
| Conventional Conventional Treatment based on current guidelines | 39 |
| Surgery Early surgery within 48 hours of randomization | 37 |
| Total | 76 |
Baseline characteristics
| Characteristic | Surgery | Conventional | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical >=65 years | 4 Participants | 9 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 29 Participants | 61 Participants |
| Age, Continuous | 46 years STANDARD_DEVIATION 15 | 48 years STANDARD_DEVIATION 17 | 47 years STANDARD_DEVIATION 16 |
| Region of Enrollment Korea, Republic of | 37 participants | 39 participants | 76 participants |
| Sex: Female, Male Female | 13 Participants | 12 Participants | 25 Participants |
| Sex: Female, Male Male | 24 Participants | 27 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 39 | 0 / 37 |
| serious Total, serious adverse events | 9 / 39 | 1 / 37 |
Outcome results
Primary
Number of Participants With In-hospital Death or Clinical Embolic Events
The composite of in-hospital death and clinical embolic events confirmed by imaging studies: the acute onset of clinical symptoms or signs of embolism and the occurrences of new lesions, as confirmed by follow-up imaging studies.
Time frame: within 6 weeks from the randomization
Population: intention to treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional | Number of Participants With In-hospital Death or Clinical Embolic Events | 9 participants |
| Surgery | Number of Participants With In-hospital Death or Clinical Embolic Events | 1 participants |
Comparison: We estimated that a sample size of 74 patients would provide 80% power to detect a significant difference with respect to the primary end point at the 2-sided significance level of 0.05, assuming that the in-hospital event rate would be 23% in the conventional treatment group and 3% in the early surgery group.p-value: <0.05Fisher Exact
Secondary
All-cause Death
Time frame: up to 6 month after enrollment
Secondary
All Embolic Events Including Symptomatic and Asymptomatic Embolization Documented by Imaging Studies
Time frame: up to 6 months after enrollment
Secondary
Readmission Due to Development of Congestive Heart Failure
Time frame: up to 6 months after enrollment
Secondary
Recurrences of Infective Endocarditis
Time frame: up to 6 months after enrollment