Echocardiography Versus no Echocardiography in S. Aureus Bacteraemia and VIRSTA Score < 3 (VIRSTA-VAL)

Echocardiography Versus no Echocardiography in Individuals With Staphylococcus Aureus Bacteremia and a VIRSTA Score <3: a Non-inferiority Randomized Controlled Trial

Staphylococcus aureus is the most frequent cause of both healthcare-associated and community-acquired bloodstream infections worldwide. Infective endocarditis (IE) has been detected in 5-17% of cases and is a determinant of poor prognosis. The investigators developed a score (the VIRSTA score) based on patients' characteristics to rule out IE with high confidence (negative predictive value (NPV) above 99%) in patients with SAB. This score, with a cut-off of 3 has been externally validated by two international studies which have also established its high NPV. The 2023 European society of cardiology (ESC) guidelines state that echocardiography should be considered in all patients with Staphylococcus aureus bacteremia (SAB) using risk scores (including VIRSTA score) to guide the use or not of echocardiography. While recommended, the investigators think that VIRSTA score must be evaluated in terms of patients' outcome.

Study Overview

• Status: Recruiting
• Conditions: Bacteremia; Staphylococcus Aureus; Infective Endocarditis
• Intervention / Treatment: Procedure: systematic echocardiography; Procedure: no echocardiography arm

Detailed Description

In the interventional arm (no-echocardiography strategy) without echocardiography, at the individual level, not performing an echocardiography will avoid a useless examination, the mobilization of the patient and the discomfort related to its performance.

In this arm, the theoretical risk is to diagnose Infective endocarditis (IE ) only at a later phase stage, i.e., at a phase of symptomatic manifestation of valve regurgitation or at the occurrence of relapse of bacteremia due to insufficient duration of antibiotic treatment. It should be noted that patients with prosthetic valve, who have "de facto" a VIRSTA score > 3, will therefore not be included in the protocol. Given the expected rarity of IE in patients with a VIRSTA score <3 and the theoretical consequences of not performing echocardiography, the primary endpoint chosen will be mortality and Staphylococcus aureus bacteraemia (SAB) relapse. The endpoint will be assessed at 90 days and not at discharge to capture relapses of inadequately treated bacteremia and the mid-term consequences of a possible delay in IE diagnosis.

On a collective scale, not performing echocardiography in many patients in whom it is not useful will allow resources to be allocated to the individuals who need it most.

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xavier Duval; Phone Number: 33 01 40 25 71 35; Email: xavier.duval@aphp.fr
• Study Contact Backup: Name: Sarah Tubiana; Phone Number: 33 01 40 25 60 51; Email: sarah.tubiana@aphp.fr

Study Locations

• France
  • Paris, France, 75018
    • Recruiting
    • Bichat Claude Bernard Hospital
    • Contact: Xavier Duval, MD, PhD; Email: xaviel.duval@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Volunteers over 18 years of age;
• Hospitalized with at least one blood culture positive for Staphylococcus aureus;
• At the time of inclusion, negative control blood culture performed 48 hours after the first Staphylococcus aureus blood culture collection;
• VIRSTA score < 3; Exclusion criteria
• Patient with catheter colonization without SAB, defined as positive blood cultures only through vascular access device specimen;
• Patient referred to the hospital for the management of IE;
• Contra indication to transthoracic echocardiography (TTE);
• Echocardiography already performed before inclusion (TTE or TEE) for the current SAB;
• Pregnancy;
• Patient under guardianship or trusteeship.
• Absence of written informed consent from the patient
• No affiliation to social security (beneficiary or assignee)
• Subject already involved in another interventional clinical research for which echocardiography must be done"

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: systematic echocardiography arm; "transthoracic echocardiography (TTE) will be performed as soon as possible within 14 days following the first blood sample collection for SAB diagnosis, completed, if required, by a transoesophageal (TEE) echocardiography based on the judgment of the echocardiographist. SAB in patients of both arms will be treated according to current recommendations, taking into account the result of the echocardiography in the control arm. "	Procedure: systematic echocardiography; "transthoracic echocardiography (TTE) will be performed as soon as possible within 14 days following the first blood sample collection for SAB diagnosis, completed, if required, by a transoesophageal (TEE) echocardiography based on the judgment of the echocardiographist. SAB in patients of both arms will be treated according to current recommendations, taking into account the result of the echocardiography in the control arm. "
Experimental: no echocardiography arm; "no echocardiography will be performed unless occurrence of new events evocating IE (extra-cardiac events or positive Staphylococcus aureus blood culture), based on the clinical judgment of the investigator. SAB in patients of both arms will be treated according to current recommendations, taking into account the result of the echocardiography in the control arm. "	Procedure: no echocardiography arm; "no echocardiography will be performed unless occurrence of new events evocating IE (extra-cardiac events or positive Staphylococcus aureus blood culture), based on the clinical judgment of the investigator. SAB in patients of both arms will be treated according to current recommendations, taking into account the result of the echocardiography in the control arm. "

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All causes mortality		90 Days
SAB relapse microbiologically confirmed	Relapse of SAB is defined in patients with bacteriologic success as the isolation of a strain of Staphylococcus aureus with in vitro antibiotic susceptibility pattern similar to that of the Staphylococcus aureus strain isolated at inclusion. Relapse will be confirmed at the end of the study by an independent adjudication committee	90 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of definite IE according to ESC 2023 criteria	An independent adjudication committee will classify definite, possible or excluded IE according to the 2023 ESC criteria	the end of hospital stay, up to 90 days
Number of definite IE according to ESC 2023 criteria		90 Days
Number of IE valvular cardiac surgery and indications (heart failure, uncontrolled infection or prevention of embolism)		the end of hospital stay, up to 90 days
Number of IE valvular cardiac surgery and indications (heart failure, uncontrolled infection or prevention of embolism)		90 Days
Length of hospitalization (days)		180 Days
All-causes mortality		180 Days
Number of SAB relapse		90 Days
Cost difference between the two strategies	Cost-effectiveness analysis if there is a difference in the number of events in each arm	90 Days
quality of life measured by EQ5D5L		180 Days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Xavier Duval, Assistance Publique - Hopitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: June 7, 2024
• First Posted (Actual): June 13, 2024

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Echocardiography; Infective endocarditis; VIRSTA score < 3; Staphylococcus aureus bacteraemia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pathological Conditions, Signs and Symptoms; Staphylococcal Infections; Bacteremia; Endocarditis
• Other Study ID Numbers: APHP220807; 2023-A01572-43 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No