Antibiotics Vs Antibiotics and Surgical ThERapy for Infective Endocarditis (ASTERIx)

Emil Loldrup Fosbol

Status: Enrolling

Conditions: Endocarditis Infective

Treatments: Procedure: Heart valve surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT05061355

H-21014406

Details and patient eligibility

About

Infective endocarditis (IE) is a deadly disease and the incidence is increasing. An important initial assessment of patients with IE includes whether surgical treatment is indicated; yet, appropriate data to guide this assessment do not exist.

The ASTERIx study will assess whether a surgical approach in addition to medical care for treatment of IE is superior to medical care alone. In total, 496 patients will be included in the study over four years. The study is event-driven and will require at least 240 events. The study will assess the primary composite outcome of death, embolization, relapse of IE, new heart failure or reinfection.

Study participants who survive to discharge will be followed by routine clinical check-ups at one- and four-weeks post-discharge and at three months. Additionally a 12-month study follow-up is planned.

The investigators will also conduct a small substudy to assess the frequency of silent emboli.

Full description

Infective endocarditis (IE) is a life-threatening disease and studies suggest that the incidence of IE has almost doubled in the last twenty years. Despite improved disease-management and diagnostics (i.e. antibiotics, surgery, and imaging techniques) IE remains a condition that is hard to diagnose and associated with high mortality (≈1/3 die within one year). Surgery is a key part of the clinical practice in IE, but the role of surgery has been greatly debated and is also used with great variation among centers. Valve repair and replacement are high-risk procedures and per-operative risk is therefore also a natural part of decision for surgery. Clinical guidelines on surgical indications have remained stable in the past decades; however, these recommendations are not based on randomized data and at the moment we are putting very sick patients with endocarditis through high-risk procedures without the proper knowledge and perhaps we refrain from surgery where benefit may be likely.

Eligible patients for study inclusion (inclusion criteria are met), will be assessed at the respective departments in Denmark where IE patients are treated (or in similar department for the international centers). All departments refer to a local endocarditis heart team at a tertiary center with cardiothoracic surgical capabilities. If no exclusion criteria exist (confirmed by the local endocarditis heart team) and the patients sign informed consent after a decent time for reflection (24 hours) then randomization will be done as soon as possible. Study participants with IE are randomized to either:

1. Medical Therapy and surgery: Standard of care treatment with antibiotics according to national and international guidelines depending on the microbiological agent and the investigators aim to perform surgery within 48 hours of randomization.
2. Medical Therapy alone with standard of care treatment with antibiotics according to guidelines depending on the microbiological agent.

Point of randomization will be in the hospital when the patient is assessed for open heart valve surgery by the heart team.

If study participants are included in the study and are randomized to the medical treatment arm of the trial, participants will stay at the local IE center and continue treatment there. If participants are randomized to surgery, the participants will be transferred to a tertiary center as soon as possible and returned to the non-surgical center for completement of treatment. After end of treatment all participants will be discharged to routinely follow-up at one- and four-weeks and at three months. Additionally, a 12 months visit will be planned for all study participants.

Enrollment: 496 estimated patients

Sex: All

Ages: 18 to 84 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Definite left-sided infective endocarditis defined by the ESC (European Society of Cardiology) modified Duke Criteria

AND

Valve vegetation =>10mm AND <=30mm with 1 or no previous embolic event during current IE case

Exclusion criteria

• Unwilling to sign informed consent
• At least one clear class I recommendation for surgery because of heart failure or uncontrolled local infection (abscess, false aneurysm, fistula)
• Unavailable for follow-up (e.g. tourist)

OR

At least one of the following criteria (unsuitable for surgery)

• Intracranial hemorrhage <1 month
• Life expectancy <1 year
• Age ≥85 years
• BMI below 15 or above 45
• Possible severe liver cirrhosis (Child-Pugh Class B or worse)
• Clinical frailty score of 5 or above
• EUROSCORE II > 50%
• Severe pulmonary disease (FEV1 (Forced expiratory volume in 1 second) or DLCO (Diffusing capacity for carbon monoxide) <30% of expected)
• Left ventricular ejection fraction (<20%)
• Technically inoperable (e.g. extracorporeal circulation deemed impossible)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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496 participants in 2 patient groups

Surgery plus medical therapy

Experimental group

Description:

Heart valve surgery will be performed as soon as possible and preferably within 48 hours of randomization in addition to standard medical care for IE.

Treatment:

Procedure: Heart valve surgery

Medical therapy

No Intervention group

Description:

Only standard medical care for IE.