Neurological Complication of Infective Endocarditis: A Prospective Multi-site Cohort Study

December 7, 2021 updated by: Basile Kerleroux, the Jeunes en Neuroradiologie Interventionnelle (JENI) research group

Neurological Complication of Infective Endocarditis: A Prospective Multi-site Cohort Study With Systematic MRI and Digital Subtraction Angiography

The main objective of this study is to better estimate the rate of infectious intracranial aneurysms (IIA) in proved infective endocarditis (IE). It also aims to identify MRI markers capable of accurately predicting (or excluding) IIA; to assess the impact of the different MRI abnormalities on the outcome; to capture the real-world management of EI with neurological complications in comprehensive IE centers in France

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Rationale:

The incidence of Infective endocarditis (IE) in developed countries is approximately 3-15 per 100,000 pers-years. Discharge mortality remains 15-30% and therapeutic management suffers in many ways from the paucity of randomized studies.(1) Symptomatic neurological complications, which occur in 15 to 30% of patients, are the most frequent extra-cardiac complication of IE and are deemed to worsen the outcome of EI.(2,3) Among this overall neurological complications, Infectious Intracranial Aneurysms (IIA) are a relatively rare, yet probably underestimate, vessel wall injury caused by septic emboli, with potentially intracranial bleeding for the patients.

Neuroimaging in the context of IE has gained wide acceptance and is encouraged in the current guidelines.(4,5) Nevertheless the benefit of early neuroimaging to optimize the initial therapeutic management remains debated.(6,7) While the appearance and the frequency of the various neurologic complications of EI are well known thanks to prospective cohort studies with systematic pre-therapeutic MRI(8-10), several clinically relevant questions are still unknow or approximate, including: 1/ What is the rate of IIA in proved EI. The current gold standard for the detection of these small and distally located aneurysms remains Digital Subtraction Angiography (DSA) and to our knowledge, there is no prospective unbiased cohort of IE with systematic DSA available in the literature. 2/ Are there MRI signs correlated with the presence of IIA on DSA? Several MRI markers such as sulcal SWI lesion or cerebral microbleeds (CMBs) with contrast enhancement look promising (10), but validation in unbiased prospective studies with systematic MRI and DSA is needed. 3/ What is the impact on the outcome of the different MRI abnormalities and of unruptured and ruptured IIA? As previously mentioned, the value of both MRI and DSA remain unclear to guide the acute therapeutic management of EI. A recent French survey highlighted differences between university Hospital in France in the management of IIA. Thus, the analysis of the current management of EI with neurological complications could also help at informing the design of future randomized trials.

Questions:

  1. Better estimate the rate of IIA in proved EI.
  2. Identify MRI markers able to accurately predict (or exclude) IIA.
  3. What is the impact of different MRI abnormalities on the outcome?
  4. Capture the real-world management of EI with neurological complications in comprehensive EI centers in France

Design and setting:

Multi-site, prospective cohort study, with standardized imaging protocol, in academic centers where MRI and DSA are performed routinely in patients with EI.

Ethics:

As for all non-interventional studies of de-identified data, written informed consent will be waived and a commitment to compliance (Reference Methodology CPMR-4) will be filed to the French data protection authority (CNIL) prior to data centralization, in respect to the General Data Protection Regulation. Patients and proxies will be informed they could oppose the use of their data for research purposes.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Multicenter, prospective cohort study of infective endocarditis in academic centers where Brain MRI and DSA are performed routinely.

Description

Inclusion Criteria:

  • patients with left-sided active infective endocarditis (IE) satisfying modified Duke Criteria,
  • patients who underwent both digital subtraction angiography (DSA) and brainMRI (as part of routine care)
  • DSA protocol with 3D rotational for both carotids and one vertebral artery
  • MRI/MRA standardized protocol including at least: Diffusion, FLAIR, 3D SWI, 3DT1SE and post gadolinium 3DT1SE and 3D TOF (large field: from the vertex to the magnum foramen).

Exclusion Criteria:

  • uncertain diagnosis of IE by infectious disease consultants
  • patients with chronic IE
  • MRI performed after the completion of Infectious intracranial aneurysms (IIA) treatment
  • MRI performed without contrast injection or complete protocol
  • More than 48-hours delay between performing MRI and DSA

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Infective endocarditis
Infective endocarditis with systematic brain MRI and digital subtraction angiography (DSA) performed routinely.
Diagnostic test: Brain MRI
Brain MRI performed routinely in patients with EI
Diagnostic test: digital subtraction angiography (DSA)
Digital Subtraction Angiography (DSA) performed routinely in patients with EI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The assess the occurrence of infectious intracranial aneurysms in proven infective endocarditis
Time Frame: 3 months
In all included cases, infectious intracranial aneurysms will be detected using cerebral Digital Subtraction Angiography (DSA), which remains the current gold standard for the detection of these small and distally located aneurysms. DSA protocol will include 2D and 3D rotational acquisitions on both carotid arteries and one vertebral artery. The number of infective endocarditis with infectious intracranial aneurysms will be referred to the total number of endocarditis to estimate the incidence of these cerebral anomalies.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the diagnostic performance of MRI markers to detect infectious intracranial aneurysms
Time Frame: 3 months
Logistic regression and Linear Discriminant Analysis (LDA) methods will be used to identify the most relevant MRI signs to predict or exclude IIA (on DSA).
3 months
To assess the predictive performance of imaging markers on clinical outcome
Time Frame: 2 years
Logistic regression will be used to identify MRI and DSA sign associated with neurological worsening at follow-up.
2 years
To assess the rate of symptomatic intracranial haemorrhage following heart surgery
Time Frame: 6 months
In case of neurological deterioration after cardiac surgery, brain imaging (MRI or NCCT) will be performed to detect the occurrence or progression of cerebral haemorrhage. Logistic regression will be used to identify the MRI and DSA signs associated with this neurological complication.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

the Jeunes en Neuroradiologie Interventionnelle (JENI) research group

Collaborators

University Hospital, Limoges
Sainte Anne Hospital (Paris)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2022

Primary Completion (Anticipated)

March 31, 2022

Study Completion (Anticipated)

June 30, 2022

Study Registration Dates

First Submitted

November 24, 2021

First Submitted That Met QC Criteria

December 7, 2021

First Posted (Actual)

December 9, 2021

Study Record Updates

Last Update Posted (Actual)

December 9, 2021

Last Update Submitted That Met QC Criteria

December 7, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JENI2021IIA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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