Acute Ischaemic STROKE: From LAboratory to the Patient's BED

NCT05725694 | Unknown

• 1 other identifier: 24055
• Study Type: observational
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Recanalization strategies have radically changed the outcome in a significant part of stroke patients. The unpredictable occurrence of cerebral edema (CE) and hemorrhagic transformation (HT) are frequent events in patients affected by ischemic stroke, even when an effective vessel recanalization has been achieved. These complications, related with blood brain barrier (BBB) disruption, remain difficult to prevent or treat, and antagonize the beneficial effect of successful recanalization, leading to poor outcome. Aim: to shed light on the reperfusion injury biological bases, this study aims at evaluating the effects of circulating and imaging biomarkers in relation to CE and HT both in stroke patients and in a coherent murine stroke model. A close interaction between clinical and preclinical research could lead to a broader understanding of the results deriving from the individual lines of activity, allowing a deeper interpretation of the underlying phenomena. Methods: The clinical setting is a retrospective observational study enrolling consecutive patients with acute ischemic stroke in the anterior circulation territory, treated with reperfusion therapies, at Careggi University Hospital in Florence (Italy) from October 1, 2015 to May 31, 2020. In this cohort, the investigators will apply a new approach to assess the presence of CE and HT after stroke in CT scans, through the quantification of anatomical distortion (AD) (induced by fluid extravasation in brain tissue) at 24 hours. A large panel of blood biomarkers related to inflammation, endothelial dysfunction , and fibrin resistance to lysis, will be measured as blood samples are taken from each patient before and 24 hours after thrombolysis or thrombectomy. The role of both AD and blood biomarkers as predictors of 3 months functional outcome, assessed by modified Rankin Scale (mRS), will be estimated. Using a translational approach the investigators will develop a new mouse model of light-induced occlusion/reperfusion of the middle cerebral artery (MCA) to better reproduce the human setting. Then, the investigators will assess functional impairment induced by stroke with and without recanalization at different time points and the investigators will assess through ex vivo experiments the insurgence of BBB alterations 24 hours after the lesion. Finally, the investigators will characterize the stroke volume and the inflammation one week after stroke.

Conditions

Acute Ischemic Stroke; Reperfusion Injury; Cerebral Edema; Hemorrhagic Transformation Due to Acute Stroke; Animal Model

Keywords

Anatomical Distortion; Blood biomarkes; Translational Stroke Research; Mouse ischemia/reperfusion stroke model

Outcome Measures

Primary Outcomes (4)

• 3 month clinical-functional outcome

  All stroke patients are followed-up 3 months after the ictal event in the out-patient clinic of Careggi University Hospital, and their functional outcome is assessed according to the modified Rankin Scale. The Modified Rankin Scale is a 6 point disability scale with possible scores ranging from 0 (no symptoms) to 5 (severe disability). A separate category of 6 is used for patients who expire.

  For each patient enrolled in the study the functional outcome is assessed 3 months after the ictal event

• The occurrence of Cerebral Edema

  Defined according to Cerebral Edema Classification used by the Helsinki Stroke Thrombolysis Registry Group (Strbian et al. 2013) on 24h Non-enhanced CT brain scan. \[CED1= Focal brain swelling up to one-third of the hemisphere; CED2= Focal brain swelling greater than one-third of the hemisphere; CED3= Brain swelling with midline shift\]

  Non-enhanced CT brain scans acquired at 24 hours after the ictal event

• The occurrence of Haemorrhagic Transformation

  Defined according to the ECASS (European Cooperative Acute Stroke Study) II radiographic classification of hemorrhagic transformation after ischemic stroke (Larrue et al. 2001) on 24h Non-enhanced CT brain scan. \[HI1: Hemorrhagic infarction type 1; HI2: Hemorrhagic infarction type 2; PH1: Parenchymal hematoma type 1; PH2: Parenchymal hematoma type 2.\]

  Non-enhanced CT brain scans acquired at 24 hours after ictal event

• The occurrence of relevant Haemorrhagic Transformation

  The presence and grading of Haemorrhagic Transformation defined as haemorrhagic infarction type two or any type of parenchymal haemorrhage (PH1 and PH2) according to ECASS II classification (Larrue et al, 2001) on 24h Non-enhanced CT brain scan. \[PH1: Parenchymal hematoma type 1; PH2: Parenchymal hematoma type 2.\]

  Non-enhanced CT brain scans acquired at 24 hours after ictal event

Secondary Outcomes (3)

• Anatomical Distortion (AD) volume (ml)

  Non-enhanced CT brain scans acquired at 2 timepoints: 1) Baseline = before rtPA administration or thrombectomy, 2) Follow-up at 24 hours

• Corrected infarct volume (ml)

  Non-enhanced CT brain scans acquired at 2 time points: 1) Baseline = before rtPA administration or thrombectomy, 2) Follow-up at 24 hours

• Relative Anatomical Distortion (AD) volume (ml)

  Non-enhanced CT brain scans acquired at 2 time points: 1) Baseline = before rtPA administration or thrombectomy, 2) Follow-up at 24 hours

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is a retrospective observational hospital-based study that will include all patients with acute ischemic stroke in the anterior circulation territory, consecutively treated either with systemic thrombolysis or endovascular thrombectomy in Careggi University Hospital, Florence, from 1 October 2015 to 31 May 2020, with available head CT scan in DICOM format performed in Careggi at baseline (before the Acute phase treatment) and follow up (approximately 24 hours). The study was approved by the local Ethics Committee (ethics committee registration number: Comitato Etico Area Vasta Centro \[CEAVC\] 16923\_oss).

You may qualify if:

• All patients with acute ischemic stroke consecutively treated (according to guidelines: Jauch et al, stroke 2013; Powers et al, Stroke 2015) either with systemic thrombolysis or endovascular thrombectomy in Careggi University Hospital, Florence, from October 1, 2015 to May 31, 2020
• With available head CT scan in DICOM format performed in Careggi at baseline (before the acute phase treatment) and at 24 hrs follow up;
• With stroke in the anterior circulation territory (according to Bamford et al, 1991);
• With informed consent to data processing

You may not qualify if:

• Patients who deny their consent to data processing;
• Baseline and follow-up clinical and radiological data consistent with stroke in the posterior circulation;
• Pregnancy;
• Age \<18 years;

Sponsors & Collaborators

• Istituto di Neuroscienze Consiglio Nazionale delle Ricerche: lead
• Careggi Hospital: collaborator
• University of Florence: collaborator

Related Publications (7)

• Piccardi B, Arba F, Nesi M, Palumbo V, Nencini P, Giusti B, Sereni A, Gadda D, Moretti M, Fainardi E, Mangiafico S, Pracucci G, Nannoni S, Galmozzi F, Fanelli A, Pezzati P, Vanni S, Grifoni S, Sarti C, Lamassa M, Poggesi A, Pescini F, Pantoni L, Gori AM, Inzitari D. Reperfusion Injury after ischemic Stroke Study (RISKS): single-centre (Florence, Italy), prospective observational protocol study. BMJ Open. 2018 May 24;8(5):e021183. doi: 10.1136/bmjopen-2017-021183.

  PMID: 29794101 BACKGROUND

• Harston GWJ, Carone D, Sheerin F, Jenkinson M, Kennedy J. Quantifying Infarct Growth and Secondary Injury Volumes: Comparing Multimodal Image Registration Measures. Stroke. 2018 Jul;49(7):1647-1655. doi: 10.1161/STROKEAHA.118.020788. Epub 2018 Jun 12.

  PMID: 29895538 BACKGROUND

• Bamford JM, Sandercock PA, Warlow CP, Slattery J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1989 Jun;20(6):828. doi: 10.1161/01.str.20.6.828. No abstract available.

  PMID: 2728057 BACKGROUND

• Balbi M, Vanni MP, Vega MJ, Silasi G, Sekino Y, Boyd JD, LeDue JM, Murphy TH. Longitudinal monitoring of mesoscopic cortical activity in a mouse model of microinfarcts reveals dissociations with behavioral and motor function. J Cereb Blood Flow Metab. 2019 Aug;39(8):1486-1500. doi: 10.1177/0271678X18763428. Epub 2018 Mar 9.

  PMID: 29521138 BACKGROUND

• Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986 May-Jun;17(3):472-6. doi: 10.1161/01.str.17.3.472.

  PMID: 3715945 BACKGROUND

• Strbian D, Meretoja A, Putaala J, Kaste M, Tatlisumak T; Helsinki Stroke Thrombolysis Registry Group. Cerebral edema in acute ischemic stroke patients treated with intravenous thrombolysis. Int J Stroke. 2013 Oct;8(7):529-34. doi: 10.1111/j.1747-4949.2012.00781.x. Epub 2012 Mar 9.

  PMID: 22405327 BACKGROUND

• Larrue V, von Kummer R R, Muller A, Bluhmki E. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke. 2001 Feb;32(2):438-41. doi: 10.1161/01.str.32.2.438.

  PMID: 11157179 BACKGROUND

Related Links

• McCarthy, Paul. (2022). FSLeyes (1.5.0). Zenodo.

Biospecimen

Retention: SAMPLES WITHOUT DNA

Patients blood is collected in tubes both with anticoagulant and without anticoagulant. Tubes are then centrifuged at room temperature at 1500 x g for 15 minutes, and the supernatant is stored in aliquots at -80° C.

MeSH Terms

Conditions

Ischemic Stroke; Reperfusion Injury; Brain Edema; Disease Models, Animal

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Animal Diseases

Study Officials

• Marzia Baldereschi, MD

  Istituto di Neuroscienze Consiglio Nazionale delle Ricerche

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2023
• First Posted: February 13, 2023
• Study Start: October 1, 2015
• Primary Completion: May 31, 2020
• Study Completion: March 31, 2023
• Last Updated: March 15, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share