Clinical trial NCT05061355: Antibiotics Vs Antibiotics and Surgical ThERapy for Infective Endocarditis
Official title: Antibiotics Vs Antibiotics and Surgical ThERapy for Infective Endocarditis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endocarditis Infective
Keywords: Surgery
Medical care
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Herlev and Gentofte Hospital
name: Bispebjerg Hospital
name: Amager Hospital
name: Nordsjaellands Hospital
name: Copenhagen University Hospital, Hvidovre
First posted: 2021-09-29
Enrollment: 496
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: All-cause mortality (Death) among study participants after randomization
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Number of study participants with clinical stroke (persisting symptoms >24 hours from onset) after randomization
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Number of study participants with systemic embolization after randomization
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Number of study participants with new endocarditis event after randomization
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Number of study participants hospitalized for Heart Failure (HF) after randomization
timeFrame: It will be assessed at discharge, and every year thereafter
Secondary outcomes:
measure: Individual components of the primary endpoint at study conclusion
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Number of study participants undergoing unplanned heart valve surgery due to IE after randomization
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Number of study participants with end-stage renal disease and in need of renal replacement therapy after randomization
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Number of study participants with either implantation of a Pacemaker or Pacemaker extraction after randomization.
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Cause-specific mortality (Death) among study participants after randomization.
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Number of days in hospital.
timeFrame: It will be assessed at discharge, and every year thereafter
measure: Clinical status at discharge
timeFrame: It will be assessed at discharge, and every year thereafter
Other outcomes:
measure: Number of study participants suffering from silent embolic event (without any clinical symptoms) after randomization
timeFrame: It will be assessed at point of randomization and 4 weeks after
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: University Hospital of Copenhagen, Rigshospitalet
city: Copenhagen
country: Denmark
facility: Amager Hvidovre Hospital
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Gentofte
country: Denmark
facility: Herlev and Gentofte Hospital
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Zealand University Hospital
city: Leipzig
country: Germany
facility: Leipzig Heart Center
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Stockholm
country: Sweden
facility: Karolinska Institutet
state: Solna
city: Linköping
country: Sweden
facility: Linköping Heart Center, University Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Emil L Fosbol, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: