Ignite Creation Date:
2024-05-06 @ 7:00 PM
Last Modification Date:
2024-10-26 @ 2:58 PM
Study NCT ID:
NCT05862025
Status:
RECRUITING
Last Update Posted:
2023-11-21
First Post:
2023-05-07
Brief Title:
Evaluation of the Usefulness of Echocardiography in Patients With Staphylococcus Aureus Bacteremia ET-AUREUS Study
Sponsor:
Puerta de Hierro University Hospital
Organization:
Puerta de Hierro University Hospital
Study Overview
Official Title:
Evaluation of the Usefulness of Echocardiography in Patients With Staphylococcus Aureus Bacteremia at Low Risk of Infective Endocarditis ET-AUREUS Study
Status:
RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ET-AUREUS
Brief Summary:
The goal of this prospective interventionist cohort study is to assess the prevalence of infective endocarditis in patients with Staphylococcus aureus bacteremia at low risk of this complication
The main questions it aims to answer are
Determine whether the risk of infective endocarditis in patients with Staphylococcus aureus bacteriemia identified as low-risk using the VIRSTA score is low enough to safely omit transthoracic or transesophageal echocardiography
Determine whether the risk of infective endocarditis in patients with Staphylococcus aureus bacteriemia in patients with no identifiable risk factor is low enough to safely omit transthoracic or transesophageal echocardiography
Calculate a cost-benefit estimate of omitting echocardiographic testing in patients identified as low-risk by means of the above methods
Participants will undergo mandatory transthoracic and transesophageal echocardiography during the first 2 weeks from Staphylococcus aureus bacteremia onset
The main questions it aims to answer are
Determine whether the risk of infective endocarditis in patients with Staphylococcus aureus bacteriemia identified as low-risk using the VIRSTA score is low enough to safely omit transthoracic or transesophageal echocardiography
Determine whether the risk of infective endocarditis in patients with Staphylococcus aureus bacteriemia in patients with no identifiable risk factor is low enough to safely omit transthoracic or transesophageal echocardiography
Calculate a cost-benefit estimate of omitting echocardiographic testing in patients identified as low-risk by means of the above methods
Participants will undergo mandatory transthoracic and transesophageal echocardiography during the first 2 weeks from Staphylococcus aureus bacteremia onset
Detailed Description:
2- Hypothesis Prospective evaluation of a cohort of patients with OAB who undergo TEE TTE will provide insight into the actual risk of IE in those patients at low risk
3- Objectives
Main objective
To estimate the prevalence of IE defined by the modified Duke criteria in patients with low risk according to the VIRSTA scale
To determine whether the risk of IE in patients with OAB identified as low risk using the VIRSTA scale is low enough to safely omit transthoracic or transesophageal echocardiography using this scale
Secondary objectives
To determine whether the risk of IE in patients with SAAB identified as low risk using the PREDICT or POSITIVE scales is low enough to safely omit transthoracic or transesophageal echocardiography
To identify risk factors for IE in patients with SAAB
Determine whether the risk of IE in patients with no risk factors is low enough to safely omit transthoracic or transesophageal echocardiography
Estimate the number of echocardiographies that could be avoided by these approaches
Estimate the cost-benefit of omitting echocardiographic testing in patients identified as low risk by the above methods
3- Material and methods
Design Multicenter prospective cohort study
Project execution sites Hospitals with the capacity to detect AFB contact the patient within 72-96h and the possibility of performing transthoracic echocardiography TTE and transesophageal echocardiography TEE in the center itself Currently 13 collaborating centers plus the sponsoring center Hospital Puerta de Hierro
Sample size calculation Sample size calculation was performed in order to estimate the prevalence of IE in patients with OAB identified as low risk using the VIRSTA scale For a confidence level of 95 with a loss rate of 10 precision of 2 and an expected proportion of 2 of IE in low-risk patients a sample size of 210 VIRSTA-negative patients was calculated Given that at inclusion it will be unknown whether the patient is VIRSTA negative and that among the objectives of the study is the identification of other subgroups of low-risk patients taking into account that approximately 45 of patients with AFB are VIRSTA negative a total sample size of 470 patients with AFB is estimated
Intervention
Systematic performance of TTE and TEE in all included patients TTE will be performed and reported first followed by TEE same or different days Both tests should be performed within 10 days of the patients inclusion in the study
The studies will be performed in each of the centers participating in the project with the latest generation echocardiographic equipment commonly used in each center All echocardiograms will be anonymized and assigned a correlative patient number
The acquisition of the images of the vegetation or infectious complication will be zoomed and 3 consecutive cardiac cycles will be recorded and sent in DICOM format both cine and image to the centralized imaging laboratory where interpretation will be performed by at least two cardiologists with expertise in echocardiography
The cardiologists interpreting the echocardiograms centrally will be blinded to any clinical microbiological and other complementary test data of the patient as well as to the local interpretation of the images The cardiologist interpreting the TTE will be blind to the TEE and vice versa
Definitions of positive echocardiographic findings for IE
Echocardiograms with at least one of the following findings will be considered positive or suggestive of IE
Vegetation echogenic mass usually mobile attached to an endocardial surface or intracardiac device Most frequently attached to a valve and with independent movement They are usually located on the ventricular side of ventriculo-arterial valves and on the atrial side of atrioventricular valves
Perivalvular abscessesinfection areas of inhomogeneous perivalvular thickening may be echodense or echolucent usually located in the valve annuli
Fistula communication between two adjacent cavities the Doppler-color passes from one cavity to another depending on the pressure in both
Pseudoaneurysm pulsatile perivalvular cavity without echoes inside into which flow enters detected by doppler-color
Perforation Destruction of the valvular surface that causes acute valvular insufficiency the valvular defect is usually seen by 2D and the insufficiency that passes through it which is usually eccentric Multiple perforations may coexist in the same valve
Endocarditis on prosthetic valve in addition to all of the above images compatible with paravalvular leak of new appearance detected with color Doppler or valve dehiscence will be considered
Predefined cutoff points to reasonably rule out IE
IE will be considered reasonably ruled out when the estimated risk of IE is low enough that the costs and risks of the tests needed for diagnosis TTE or TEE outweigh the benefits
In defining cutoff points for this low risk of IE we consider several recent publications that estimate the risk of IE above which a patient benefits from such evaluations 824 as well as the usefulness of the negative likelihood ratio LR- or likelihood ratio - in predicting this risk as has been reported by other authors 25 In line with these studies the following cut-off points are predefined
1 If the risk of IE was less than 05 and the CP- of the scale less than 005 IE would be considered reasonably ruled out without the need for any echocardiographic assessment
2 If the risk of IE was between 05-2 or the CP- of the scale between 005-010 IE would be considered reasonably ruled out without the need for TEE when a negative TTE with good visualization of the heart valves is available
3 If the risk of IE was between 2-5 or the CP- of the scale between 010-020 IE could be considered reasonably ruled out with a negative TTE without the need for TEE only if the prevalence of IE after TTE was less than 1 Otherwise the use of TEE would be considered necessary
4 If the risk of IE was greater than 5 or the CP- of the scale was greater than 020 TEE would be considered necessary to safely rule out IE
Variables to be studied
Demographic data comorbidities mode of acquisition and primary focus of bacteremia clinical microbiological echocardiographic and evolution data from patients medical records as well as echocardiographic findings will be collected Data will be collected from the electronic history of each center and included in an anonymized form in an online medical database platform eCDR
Statistical analysis Quantitative variables will be presented as median and 25th and 75th percentiles and qualitative variables by absolute and relative frequencies
An interval estimation 95 of the prevalence of IE in patients identified as low risk will be performed using the VIRSTA PREDICT and POSITIVE scales The prevalence of IE in patients without any of the identified factors will also be estimated using secondary analyses see below The diagnostic validity indices sensitivity specificity negative PC- and positive PC likelihood ratios and negative NPV and positive predictive values PPV vs the gold standard modified Duke criteria will be estimated With these data we will estimate the risk of IE in an identified low-risk patient from a population with a prevalence similar to ours Echocardiography TTE andor TEE will be considered dispensable in patients with SAAB when the estimated risk of IE in patients identified as low risk and the CP- of the scale is below the aforementioned predefined cut-off points
For the study of IE risk factors univariate inferential analysis will be performed using the Mann-Whitney U test for quantitative variables and with the χ2 test or Fishers exact test when necessary for qualitative variables Those variables that are clinically and statistically significant will be included in a multivariate logistic regression model
Finally the number of echocardiographic tests both TTE and TEE that could have been safely omitted using the different approaches will be estimated For the cost-benefit study the following risks will be taken into account increased mortality due to nondiagnosis of IE 15 2 increased mortality due to TEE 01 3 increased mortality due to TTE 0 The costs of performing tests are estimated following the catalog of public prices of the Community of Madrid Order 7272017 cost TEE 80
Bilateral p-values of less than 005 will be considered statistically significant All statistical analyses will be performed using the SPSS version 25 software package
3- Objectives
Main objective
To estimate the prevalence of IE defined by the modified Duke criteria in patients with low risk according to the VIRSTA scale
To determine whether the risk of IE in patients with OAB identified as low risk using the VIRSTA scale is low enough to safely omit transthoracic or transesophageal echocardiography using this scale
Secondary objectives
To determine whether the risk of IE in patients with SAAB identified as low risk using the PREDICT or POSITIVE scales is low enough to safely omit transthoracic or transesophageal echocardiography
To identify risk factors for IE in patients with SAAB
Determine whether the risk of IE in patients with no risk factors is low enough to safely omit transthoracic or transesophageal echocardiography
Estimate the number of echocardiographies that could be avoided by these approaches
Estimate the cost-benefit of omitting echocardiographic testing in patients identified as low risk by the above methods
3- Material and methods
Design Multicenter prospective cohort study
Project execution sites Hospitals with the capacity to detect AFB contact the patient within 72-96h and the possibility of performing transthoracic echocardiography TTE and transesophageal echocardiography TEE in the center itself Currently 13 collaborating centers plus the sponsoring center Hospital Puerta de Hierro
Sample size calculation Sample size calculation was performed in order to estimate the prevalence of IE in patients with OAB identified as low risk using the VIRSTA scale For a confidence level of 95 with a loss rate of 10 precision of 2 and an expected proportion of 2 of IE in low-risk patients a sample size of 210 VIRSTA-negative patients was calculated Given that at inclusion it will be unknown whether the patient is VIRSTA negative and that among the objectives of the study is the identification of other subgroups of low-risk patients taking into account that approximately 45 of patients with AFB are VIRSTA negative a total sample size of 470 patients with AFB is estimated
Intervention
Systematic performance of TTE and TEE in all included patients TTE will be performed and reported first followed by TEE same or different days Both tests should be performed within 10 days of the patients inclusion in the study
The studies will be performed in each of the centers participating in the project with the latest generation echocardiographic equipment commonly used in each center All echocardiograms will be anonymized and assigned a correlative patient number
The acquisition of the images of the vegetation or infectious complication will be zoomed and 3 consecutive cardiac cycles will be recorded and sent in DICOM format both cine and image to the centralized imaging laboratory where interpretation will be performed by at least two cardiologists with expertise in echocardiography
The cardiologists interpreting the echocardiograms centrally will be blinded to any clinical microbiological and other complementary test data of the patient as well as to the local interpretation of the images The cardiologist interpreting the TTE will be blind to the TEE and vice versa
Definitions of positive echocardiographic findings for IE
Echocardiograms with at least one of the following findings will be considered positive or suggestive of IE
Vegetation echogenic mass usually mobile attached to an endocardial surface or intracardiac device Most frequently attached to a valve and with independent movement They are usually located on the ventricular side of ventriculo-arterial valves and on the atrial side of atrioventricular valves
Perivalvular abscessesinfection areas of inhomogeneous perivalvular thickening may be echodense or echolucent usually located in the valve annuli
Fistula communication between two adjacent cavities the Doppler-color passes from one cavity to another depending on the pressure in both
Pseudoaneurysm pulsatile perivalvular cavity without echoes inside into which flow enters detected by doppler-color
Perforation Destruction of the valvular surface that causes acute valvular insufficiency the valvular defect is usually seen by 2D and the insufficiency that passes through it which is usually eccentric Multiple perforations may coexist in the same valve
Endocarditis on prosthetic valve in addition to all of the above images compatible with paravalvular leak of new appearance detected with color Doppler or valve dehiscence will be considered
Predefined cutoff points to reasonably rule out IE
IE will be considered reasonably ruled out when the estimated risk of IE is low enough that the costs and risks of the tests needed for diagnosis TTE or TEE outweigh the benefits
In defining cutoff points for this low risk of IE we consider several recent publications that estimate the risk of IE above which a patient benefits from such evaluations 824 as well as the usefulness of the negative likelihood ratio LR- or likelihood ratio - in predicting this risk as has been reported by other authors 25 In line with these studies the following cut-off points are predefined
1 If the risk of IE was less than 05 and the CP- of the scale less than 005 IE would be considered reasonably ruled out without the need for any echocardiographic assessment
2 If the risk of IE was between 05-2 or the CP- of the scale between 005-010 IE would be considered reasonably ruled out without the need for TEE when a negative TTE with good visualization of the heart valves is available
3 If the risk of IE was between 2-5 or the CP- of the scale between 010-020 IE could be considered reasonably ruled out with a negative TTE without the need for TEE only if the prevalence of IE after TTE was less than 1 Otherwise the use of TEE would be considered necessary
4 If the risk of IE was greater than 5 or the CP- of the scale was greater than 020 TEE would be considered necessary to safely rule out IE
Variables to be studied
Demographic data comorbidities mode of acquisition and primary focus of bacteremia clinical microbiological echocardiographic and evolution data from patients medical records as well as echocardiographic findings will be collected Data will be collected from the electronic history of each center and included in an anonymized form in an online medical database platform eCDR
Statistical analysis Quantitative variables will be presented as median and 25th and 75th percentiles and qualitative variables by absolute and relative frequencies
An interval estimation 95 of the prevalence of IE in patients identified as low risk will be performed using the VIRSTA PREDICT and POSITIVE scales The prevalence of IE in patients without any of the identified factors will also be estimated using secondary analyses see below The diagnostic validity indices sensitivity specificity negative PC- and positive PC likelihood ratios and negative NPV and positive predictive values PPV vs the gold standard modified Duke criteria will be estimated With these data we will estimate the risk of IE in an identified low-risk patient from a population with a prevalence similar to ours Echocardiography TTE andor TEE will be considered dispensable in patients with SAAB when the estimated risk of IE in patients identified as low risk and the CP- of the scale is below the aforementioned predefined cut-off points
For the study of IE risk factors univariate inferential analysis will be performed using the Mann-Whitney U test for quantitative variables and with the χ2 test or Fishers exact test when necessary for qualitative variables Those variables that are clinically and statistically significant will be included in a multivariate logistic regression model
Finally the number of echocardiographic tests both TTE and TEE that could have been safely omitted using the different approaches will be estimated For the cost-benefit study the following risks will be taken into account increased mortality due to nondiagnosis of IE 15 2 increased mortality due to TEE 01 3 increased mortality due to TTE 0 The costs of performing tests are estimated following the catalog of public prices of the Community of Madrid Order 7272017 cost TEE 80
Bilateral p-values of less than 005 will be considered statistically significant All statistical analyses will be performed using the SPSS version 25 software package
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None