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

Endocarditis, Bacterial Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05152225
• Other study ID #: JENI2021IIA
• Status: Not yet recruiting
• Start date: January 1, 2022
• Est. completion date: June 30, 2022

Study information

• Verified date: December 2021
• Source: the Jeunes en Neuroradiologie Interventionnelle (JENI) research group
• Contact: Basile Kerleroux, MD-MSc
• Phone: +33145648222
• Email: basile.kerleroux[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: June 30, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Aneurysm
• Endocarditis
• Endocarditis, Bacterial
• Intracranial Aneurysm

Intervention

Diagnostic Test:
• Brain MRI
Brain MRI performed routinely in patients with EI
• digital subtraction angiography (DSA)
Digital Subtraction Angiography (DSA) performed routinely in patients with EI

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
the Jeunes en Neuroradiologie Interventionnelle (JENI) research group	Sainte Anne Hospital (Paris), University Hospital, Limoges

References & Publications (8)

Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Tleyjeh IM, Rybak MJ, Barsic B, Lockhart PB, Gewitz MH, Levison ME, Bolger AF, Steckelberg JM, Baltimore RS, Fink AM, O'Gara P, Taubert KA; American Heart Association Committee on Rheumatic Fever, Endocarditi — View Citation

Carneiro TS, Awtry E, Dobrilovic N, Fagan MA, Kimmel S, Weinstein ZM, Cervantes-Arslanian AM. Neurological Complications of Endocarditis: A Multidisciplinary Review with Focus on Surgical Decision Making. Semin Neurol. 2019 Aug;39(4):495-506. doi: 10.1055 — View Citation

Cho SM, Rice C, Marquardt RJ, Zhang LQ, Khoury J, Thatikunta P, Buletko AB, Hardman J, Uchino K, Wisco D; Infective Endocarditis Strokes and Imaging Characteristics (IESIC) group. Magnetic Resonance Imaging Susceptibility-Weighted Imaging Lesion and Contr — View Citation

García-Cabrera E, Fernández-Hidalgo N, Almirante B, Ivanova-Georgieva R, Noureddine M, Plata A, Lomas JM, Gálvez-Acebal J, Hidalgo-Tenorio C, Ruíz-Morales J, Martínez-Marcos FJ, Reguera JM, de la Torre-Lima J, de Alarcón González A; Group for the Study of — View Citation

Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, Dulgheru R, El Khoury G, Erba PA, Iung B, Miro JM, Mulder BJ, Plonska-Gosciniak E, Price S, Roos-Hesselink J, Snygg-Martin U, Thuny F, Tornos Mas P, Vilacosta I, Zamorano JL; ESC S — View Citation

Iung B, Tubiana S, Klein I, Messika-Zeitoun D, Brochet E, Lepage L, Al-Attar N, Ruimy R, Leport C, Wolff M, Duval X; ECHO-IMAGE Study Group. Determinants of cerebral lesions in endocarditis on systematic cerebral magnetic resonance imaging: a prospective — View Citation

Migdady I, Rice CJ, Hassett C, Zhang LQ, Wisco D, Uchino K, Cho SM. MRI Presentation of Infectious Intracranial Aneurysms in Infective Endocarditis. Neurocrit Care. 2019 Jun;30(3):658-665. doi: 10.1007/s12028-018-0654-1. — View Citation

Snygg-Martin U, Gustafsson L, Rosengren L, Alsiö A, Ackerholm P, Andersson R, Olaison L. Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical br — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The assess the occurrence of infectious intracranial aneurysms in proven infective endocarditis	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	To assess the diagnostic performance of MRI markers to detect infectious intracranial aneurysms	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
Secondary	To assess the predictive performance of imaging markers on clinical outcome	Logistic regression will be used to identify MRI and DSA sign associated with neurological worsening at follow-up.	2 years
Secondary	To assess the rate of symptomatic intracranial haemorrhage following heart surgery	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