Clinical trial NCT01079728: Prediction of Stroke-associated Pneumonia
Official title: Prediction of Stroke-associated Pneumonia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ischemic Stroke
Keywords: ischemic stroke
stroke-associated pneumonia
prediction
immune and infection parameters
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Siemens Health Care
name: NeuroCure Clinical Research Center, Charite, Berlin
First posted: 2010-03-03
Enrollment: 486
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: ischemic stroke in the anterior (ACA, MCA) and posterior cerebral circulation (PCA, BA) of any severity in the last 36h

Brief summary: Stroke-associated pneumonia (SAP) constitutes a clinically relevant complication of stroke, because it increases the mortality and has a negative impact on the neurological prognosis of the patient.

An early identification of patients at risk for SAP allowing an early initiation of antiinfective therapy may improve the prognosis. To date, no reliable prediction models or clinical scores for stroke-associated pneumonia exist. Recently, it was shown that parameters indicating an impaired immune function are associated with the subsequent occurrence of SAP and could therefore be used as predictors for SAP.

This study will develop and prospectively validate a prognostic score to predict SAP based on clinical parameters. Furthermore, the study examines the prognostic properties of selected immune and infectious parameters for the prediction and diagnosis of SAP. The study will further address the question whether these infectious and immune parameters predict the 3-month-outcome. In a subgroup of patients, MRI parameters on stroke size and localization will be assessed to investigate whether these parameters might allow prediction of SAP or the 3-month-outcome.


Eligibility criteria: Inclusion Criteria:

* ischemic stroke in the anterior (ACA, MCA) and posterior cerebral circulation (PCA, BA) of any severity
* stroke onset within the last 36h
* age ≥ 18
* consent by the patient or the legal representative

Exclusion Criteria:

* intracranial hemorrhage
* signs of infection at admission (clinical / paraclinical)
* pre-existing dysphagia
* mechanical ventilation at admission
* participation in an interventional trial

Primary outcomes:
measure: Predictive score for SAP based on clinical parameters assessed within 36h after stroke onset
timeFrame: SAP within 7 days after onset of symptoms (stroke)
measure: Predictive properties of immune parameters (IL6, IL10, mHLA-DR) or infection parameters (PCT) for the occurrence of a SAP within 7 days after stroke onset
timeFrame: SAP within 7 days after onset of symptoms (stroke)
Secondary outcomes:
measure: Predictive properties of immune parameters (IL6, IL8, IL10, mHLA-DR, MBL, monocytic cytokine secretion after ex vivo stimulation, C5a) and infection parameters (PCT, LBP) for the neurological outcome
timeFrame: Neurological outcome 3 months after onset of symptoms (stroke)
measure: Plasma levels of acetylcholinesterase
timeFrame: within 7 days after onset of symptoms (stroke)
measure: Localization and stroke volume analysis
timeFrame: SAP within 7 days and neurological outcome after 3 months after onset of symptoms (stroke)
measure: Predictive properties of immune parameters (IL6, IL8, IL10, mHLA-DR, MBL, monocytic cytokine secretion after ex vivo stimulation, C5a) and infection parameters (PCT, LBP) for the occurence of a SAP
timeFrame: SAP within 7 days after onset of symptoms (stroke)
measure: Influence of insular cortex involvement and infarct volume on the occurrence of a SAP within 7 days and and on the neurological outcome after 3 months
timeFrame: SAP within 7 days after onset of symptoms (stroke) and neurological outcome after 3 months
measure: Transcriptome analyses
timeFrame: SAP within 7 days and neurological outcome after 3 months after onset of symptoms (stroke)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite University (Center for Stroke Research Berlin CSB & NeuroCure Clinical Research Center NCRC)
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin, Neurologie
city: Berlin
country: Germany
facility: Vivantes Auguste Viktoria Klinikum Neurologie
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain Neurologie
city: Berlin
country: Germany
facility: Vivantes Klinikum Spandau Neurologie
city: Berlin
country: Germany
facility: Vivantes Neukölln Neurologie
city: Potsdam
country: Germany
facility: Sankt Josefs Krankenhaus Potsdam Neurologie
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
Study officials:
affiliation: Charite University Berlin (Center for Stroke Research Berlin CSB & NeuroCure Clinical Research Center NCRC)
name: Andreas Meisel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité University Berlin (Center for Stroke Research Berlin CSB)
name: Peter Heuschmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoffmann S, Harms H, Ulm L, Nabavi DG, Mackert BM, Schmehl I, Jungehulsing GJ, Montaner J, Bustamante A, Hermans M, Hamilton F, Gohler J, Malzahn U, Malsch C, Heuschmann PU, Meisel C, Meisel A; PREDICT Investigators. Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study. J Cereb Blood Flow Metab. 2017 Dec;37(12):3671-3682. doi: 10.1177/0271678X16671964. Epub 2016 Oct 14.
citation: Hotter B, Hoffmann S, Ulm L, Meisel C, Bustamante A, Montaner J, Katan M, Smith CJ, Meisel A. External Validation of Five Scores to Predict Stroke-Associated Pneumonia and the Role of Selected Blood Biomarkers. Stroke. 2021 Jan;52(1):325-330. doi: 10.1161/STROKEAHA.120.031884. Epub 2020 Dec 7.
citation: Hotter B, Hoffmann S, Ulm L, Meisel C, Fiebach JB, Meisel A. IL-6 Plasma Levels Correlate With Cerebral Perfusion Deficits and Infarct Sizes in Stroke Patients Without Associated Infections. Front Neurol. 2019 Feb 15;10:83. doi: 10.3389/fneur.2019.00083. eCollection 2019.
citation: Hotter B, Hoffmann S, Ulm L, Montaner J, Bustamante A, Meisel C, Meisel A. Inflammatory and stress markers predicting pneumonia, outcome, and etiology in patients with stroke: Biomarkers for predicting pneumonia, functional outcome, and death after stroke. Neurol Neuroimmunol Neuroinflamm. 2020 Feb 25;7(3):e692. doi: 10.1212/NXI.0000000000000692. Print 2020 May.
citation: Mengel A, Ulm L, Hotter B, Harms H, Piper SK, Grittner U, Montaner J, Meisel C, Meisel A, Hoffmann S. Biomarkers of immune capacity, infection and inflammation are associated with poor outcome and mortality after stroke - the PREDICT study. BMC Neurol. 2019 Jul 3;19(1):148. doi: 10.1186/s12883-019-1375-6.
citation: Winek K, Lobentanzer S, Nadorp B, Dubnov S, Dames C, Jagdmann S, Moshitzky G, Hotter B, Meisel C, Greenberg DS, Shifman S, Klein J, Shenhar-Tsarfaty S, Meisel A, Soreq H. Transfer RNA fragments replace microRNA regulators of the cholinergic poststroke immune blockade. Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32606-32616. doi: 10.1073/pnas.2013542117. Epub 2020 Dec 7.