Antibiotics Vs Antibiotics and Surgical ThERapy for Infective Endocarditis

NCT05061355 | Recruiting DMC

• 1 other identifier: H-21014406
• Study Type: interventional
• Target: 496
• Locations: 4 countries
• Sites: 15

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.

Conditions

Endocarditis Infective

Keywords

Surgery; Medical care

Outcome Measures

Primary Outcomes (5)

• All-cause mortality (Death) among study participants after randomization

  The incidence of all-cause mortality will be compared between treatment groups (medical therapy vs. medical therapy + surgery). \[Date on all-mortality will be assessed in the ASTERIx study database REDCap (electronic Case Report File (eCRF)) and all information in the database are gathered from the study participants medical records\].

  It will be assessed at discharge, and every year thereafter

• Number of study participants with clinical stroke (persisting symptoms >24 hours from onset) after randomization

  The incidence of stroke with corresponding clinical signs of stroke (e.g., sudden numbness or weakness of the face, arm or leg, typically in one side of the body, confusion: trouble speaking or understanding speech etc.). \[The information on clinical stroke are assessed in the study participants medical records which contains information on imaging modalities and this information are entered in the ASTERIx REDCap database. \]

  It will be assessed at discharge, and every year thereafter

• Number of study participants with systemic embolization after randomization

  New embolic event (with corresponding symptoms from the affected organ/organs), to one of the following organs: * Brain * Kidney * Spleen * Eyes or * Extremities \[Information on embolic events are gathered from study participants medical records which includes imaging modalities e.g., PET-CT. Information on new embolic events will be entered in ASTERIx REDCap database, only date of first embolic event after randomization are entered into REDCap.\]

  It will be assessed at discharge, and every year thereafter

• Number of study participants with new endocarditis event after randomization

  The incidence of new endocarditis event after randomization are defined as followed: * Relapse of bacteria with the same organism \> 7 days after study intervention * Vegetation enlargement (\>50%) or local spreading of infection assessed by echocardiography . * Re-infection after complete treatment for the initial endocarditis episode. \[All the listed outcomes defining new endocarditis event will be assessed from study participants medical records including information from the Danish Microbiology Database and entered into ASTERIx REDCap database\]

  It will be assessed at discharge, and every year thereafter

• Number of study participants hospitalized for Heart Failure (HF) after randomization

  The incidence of hospitalization for Heart Failure among study participants. \[Information are gathered from medical records and entered into ASTERIx REDCap database\].

  It will be assessed at discharge, and every year thereafter

Secondary Outcomes (7)

• Individual components of the primary endpoint at study conclusion

  It will be assessed at discharge, and every year thereafter

• Number of study participants undergoing unplanned heart valve surgery due to IE after randomization

  It will be assessed at discharge, and every year thereafter

• Number of study participants with end-stage renal disease and in need of renal replacement therapy after randomization

  It will be assessed at discharge, and every year thereafter

• Number of study participants with either implantation of a Pacemaker or Pacemaker extraction after randomization.

  It will be assessed at discharge, and every year thereafter

• Cause-specific mortality (Death) among study participants after randomization.

  It will be assessed at discharge, and every year thereafter

Other Outcomes (1)

• Number of study participants suffering from silent embolic event (without any clinical symptoms) after randomization

  It will be assessed at point of randomization and 4 weeks after

Study Arms (2)

Surgery plus medical therapy

EXPERIMENTAL

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.

Procedure: Heart valve surgery

Medical therapy

NO INTERVENTION

Only standard medical care for IE.

Interventions

Heart valve surgery PROCEDURE

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

Surgery plus medical therapy

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• Emil Loldrup Fosbol: lead
• Herlev and Gentofte Hospital: collaborator
• Bispebjerg Hospital: collaborator
• Amager Hospital: collaborator
• Nordsjaellands Hospital: collaborator
• Copenhagen University Hospital, Hvidovre: collaborator

Study Sites (15)

Aalborg University Hospital

Aalborg, Denmark

RECRUITING

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

University Hospital of Copenhagen, Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Amager Hvidovre Hospital

Copenhagen, Denmark

RECRUITING

Bispebjerg Hospital

Copenhagen, Denmark

RECRUITING

Herlev and Gentofte Hospital

Gentofte Municipality, Denmark

RECRUITING

Nordsjællands Hospital

Hillerød, Denmark

RECRUITING

Odense University Hospital

Odense, Denmark

RECRUITING

Zealand University Hospital

Roskilde, Denmark

RECRUITING

Leipzig Heart Center

Leipzig, 04289, Germany

RECRUITING

Amsterdam University Medical Center

Amsterdam, 1105, Netherlands

RECRUITING

Catharina Hospital

Eindhoven, 5623, Netherlands

RECRUITING

Leiden University Medical Center

Leiden, Netherlands

RECRUITING

Karolinska Institutet

Stockholm, Solna, 17177, Sweden

RECRUITING

Linköping Heart Center, University Hospital

Linköping, 581 85, Sweden

RECRUITING

MeSH Terms

Conditions

Endocarditis

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Emil L Fosbol, MD, Ph.D

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emil L Fosbol, MD, Ph.D

CONTACT

+45 354 56340; emil.fosboel@regionh.dk

Peter L Graversen, MD

CONTACT

+45 354 58698; peter.laursen.graversen@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: September 29, 2021
• Study Start: September 9, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 14, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (9); NL (3); SE (2); DE (1)