Prediction of Stroke-associated Pneumonia (PREDICT)

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke

• Study Type: Observational
• Enrollment (Actual): 486

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Vivantes Auguste Viktoria Klinikum Neurologie
  • Berlin, Germany
    • Vivantes Neukölln Neurologie
  • Berlin, Germany, 10117
    • Charite University (Center for Stroke Research Berlin CSB & NeuroCure Clinical Research Center NCRC)
  • Berlin, Germany
    • Unfallkrankenhaus Berlin, Neurologie
  • Berlin, Germany
    • Vivantes Klinikum im Friedrichshain Neurologie
  • Berlin, Germany
    • Vivantes Klinikum Spandau Neurologie
  • Potsdam, Germany
    • Sankt Josefs Krankenhaus Potsdam Neurologie
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ischemic stroke patients; patients with an ischemic stroke in the anterior (ACA, MCA) and posterior flow area (PCA, BA) of any severity in the last 36h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive score for SAP based on clinical parameters assessed within 36h after stroke onset	To establish a predictive score for SAP based on clinical parameters assessed within 36h after stroke onset	SAP within 7 days after onset of symptoms (stroke)
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	To evaluate of the 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	SAP within 7 days after onset of symptoms (stroke)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	To evaluate of the 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	Neurological outcome 3 months after onset of symptoms (stroke)
Plasma levels of acetylcholinesterase	To investigate the parasympathetic influence on the immune function after stroke by measuring plasma levels of acetylcholinesterase	within 7 days after onset of symptoms (stroke)
Localization and stroke volume analysis	To investigate the influence of the localization and stroke volume on the occurrence of a SAP and on neurological outcome	SAP within 7 days and neurological outcome after 3 months after onset of symptoms (stroke)
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	To evaluate of the 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	SAP within 7 days after onset of symptoms (stroke)
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	To investigate the influence of insular cortex involvement and infarct volume on the occurrence of a SAP within 7 days after stroke onset and on the neurological outcome after 3 months	SAP within 7 days after onset of symptoms (stroke) and neurological outcome after 3 months
Transcriptome analyses	To perform transcriptome analyses to identify new biomarkers which may predict the occurence of a SAP or the 3-month neurological outcome	SAP within 7 days and neurological outcome after 3 months after onset of symptoms (stroke)

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: NeuroCure Clinical Research Center, Charite, Berlin; Siemens Health Care
• Investigators: Principal Investigator: Peter Heuschmann, MD, Charité University Berlin (Center for Stroke Research Berlin CSB)

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (ACTUAL): January 1, 2013
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: March 2, 2010
• First Submitted That Met QC Criteria: March 2, 2010
• First Posted (ESTIMATE): March 3, 2010

Study Record Updates

• Last Update Posted (ACTUAL): January 4, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: ischemic stroke; prediction; immune and infection parameters; stroke-associated pneumonia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Stroke; Ischemic Stroke; Pneumonia
• Other Study ID Numbers: PREDICT (CardioDx)