Antibiotics Vs Antibiotics and Surgical ThERapy for Infective Endocarditis

NCT ID: NCT05061355

Last Updated: 2024-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

496 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-09

Study Completion Date

2026-06-01

Brief Summary

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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

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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.

Conditions

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Endocarditis Infective

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Surgery plus medical therapy

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.

Group Type EXPERIMENTAL

Heart valve surgery

Intervention Type PROCEDURE

Heart valve surgery will be performed as soon as possible and preferably within 48 hours

Medical therapy

Only standard medical care for IE.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Heart valve surgery

Heart valve surgery will be performed as soon as possible and preferably within 48 hours

Intervention Type PROCEDURE

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

84 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Herlev and Gentofte Hospital

OTHER

Sponsor Role collaborator

Bispebjerg Hospital

OTHER

Sponsor Role collaborator

Amager Hospital

OTHER

Sponsor Role collaborator

Nordsjaellands Hospital

OTHER

Sponsor Role collaborator

Copenhagen University Hospital, Hvidovre

OTHER

Sponsor Role collaborator

Emil Loldrup Fosbol

OTHER

Sponsor Role lead

Responsible Party

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Emil Loldrup Fosbol

MD, PhD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Emil L Fosbol, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Locations

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Aalborg University Hospital

Aalborg, , Denmark

Site Status RECRUITING

Aarhus University Hospital

Aarhus, , Denmark

Site Status RECRUITING

University Hospital of Copenhagen, Rigshospitalet

Copenhagen, , Denmark

Site Status RECRUITING

Amager Hvidovre Hospital

Copenhagen, , Denmark

Site Status RECRUITING

Bispebjerg Hospital

Copenhagen, , Denmark

Site Status RECRUITING

Herlev and Gentofte Hospital

Gentofte Municipality, , Denmark

Site Status RECRUITING

Nordsjællands Hospital

Hillerød, , Denmark

Site Status RECRUITING

Odense University Hospital

Odense, , Denmark

Site Status RECRUITING

Zealand University Hospital

Roskilde, , Denmark

Site Status RECRUITING

Leipzig Heart Center

Leipzig, , Germany

Site Status RECRUITING

Amsterdam University Medical Center

Amsterdam, , Netherlands

Site Status RECRUITING

Catharina Hospital

Eindhoven, , Netherlands

Site Status RECRUITING

Leiden University Medical Center

Leiden, , Netherlands

Site Status RECRUITING

Karolinska Institutet

Stockholm, Solna, Sweden

Site Status RECRUITING

Linköping Heart Center, University Hospital

Linköping, , Sweden

Site Status RECRUITING

Countries

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Denmark Germany Netherlands Sweden

Central Contacts

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Emil L Fosbol, MD, Ph.D

Role: CONTACT

+45 354 56340

Peter L Graversen, MD

Role: CONTACT

+45 354 58698

Facility Contacts

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Hanne S Jensen, MD

Role: primary

Jonas Povlsen

Role: primary

Emil Fosbøl, MD, PhD

Role: primary

+4535456340

Ekim Seven, MD

Role: primary

Nana Køber, MD

Role: primary

Kasper Iversen, MD

Role: primary

Malene Wienberg, MD

Role: primary

Kenneth Pedersen, MD

Role: primary

Niels E Bruun, MD

Role: primary

Maren A Zieger, Study Coordinator

Role: primary

+49 341 865-251545

Role: backup

Michael A Borger

Role: backup

Henneke Gerritsen, Research Nurse/Coordinator Ca

Role: primary

+31 (0) 20 - 444 44 45

Jasper L Selder, MD

Role: backup

Ingrid Aarts, Research Coordinator

Role: primary

040 - 239 83 60

Kayan Lam, MD

Role: backup

Jesper Hjortnaes, MD

Role: primary

Madeleine Dewerand, Research Coordinator

Role: primary

+46 8-524 833 73

Christian Olsson, MD, PhD

Role: backup

Nina Hallsten, MD

Role: primary

072-4638242

Farkas Vánky, MD

Role: backup

Other Identifiers

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H-21014406

Identifier Type: -

Identifier Source: org_study_id

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