COAgulation Disorders in Ischaemic and Haemorrhagic Stroke (COADIHS)

In this study the investigators will assess both procoagulant and anticoagulant pathways using thrombin generation and platelet function tests; as well as neuronal ischemia using cell free DNA in all patients presenting with ischaemic and haemorrhagic stroke (including aneurysmal subarachnoid haemorraghe). Also the cross-talk between inflammation and thrombosis, so-called thrombo-inflammation is further investigated. As such the investigators aim to characterise the patient's coagulation profile before administration of any treatment. By assessing these pathways the investigators strive to detect specific markers to predict vital and functional outcome at 3 months in these patients. Finally the investigators may provide new pathophysiological insights in the course of disease following these events that can possibly improve future therapeutic strategies.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Aneurysmal Subarachnoid Hemorrhage; Haemorrhagic Stroke
• Intervention / Treatment: Diagnostic test: blood sampling

Detailed Description

In the COADIHS trial the main objective is to map the coagulation profile, both procoagulant and anticoagulant pathways, in patients presenting with acute ischaemic or haemorrhagic stroke.

By assessing these different pathways the investigators aim to detect possible biomarkers of coagulation with predictive value for functional and vital outcome at 3 months.

In different subgroup analyses the investigators try to answer additional research questions as posed by the specific pathophysiology.

Primary Objective:

Mapping the coagulation profile of both procoagulant and anticoagulant pathways together with markers of inflammation and ischemia in patients presenting with all types of acute ischaemic or haemorrhagic stroke, at presentation and during first 7 days of clinical course in order to detect biochemical markers with predictive value of vital and functional outcome at 3 months.

Secondary Objective:

• Detection of culprit underlying thrombophilia in cryptogenic stroke and evaluation of their effect on clinical course and outcome (recurrent stroke).
• Evaluating the interaction between the coagulation profile and pre-stroke medication that works on coagulation pathways.
• To investigate the role of platelets and platelet activation in different pathophysiological mechanisms described in development of delayed cerebral ischemia following aneurysmal subarachnoid haemorrhage (aSAH)(microvessel constriction, thromboinflammation, large artery vasospasm, cortical spreading depolarization)
• To evaluate the role of haemostatic derangements following aSAH as biomarker to predict delayed cerebral ischemia.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Hendrik Stragier, MD; Phone Number: +3289325277; Email: hendrik.stragier@zol.be

Study Locations

• Belgium
  • Genk, Belgium, 3600
    • Recruiting
    • Ziekenhuis Oost-Limburg
    • Contact: Hendrik Stragier, MD; Phone Number: +3289325277; Email: hendrik.stragier@zol.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population will consist of patients presenting at the hospital with ischaemic stroke, haemorrhagic stroke or aneurysmal subarachnoid haemorrhage.

As our hospital is a referral centre, both referred patients and patients presenting at our emergency department will be screened for eligibility.

Description

Inclusion Criteria:

Presenting at the hospital with ischaemic stroke, haemorrhagic stroke, aneurysmal subarachnoid haemorrhage or any other type of non-traumatic, intracranial bleeding

In patients with minor ischemic stroke (NIHSS <= 4) only baseline lab sampling will be performed (T0 and T0B).

Exclusion Criteria:

• Refusal of participation by patient or legal representative
• Traumatic intracranial (subdural, subarachnoid, epidural haematoma) bleeding
• Patients receiving treatment with interference on coagulation (pro / anti) before first sampling: in this group of patients the coagulation assessment at presentation will be excluded, further lab sampling is performed according to protocol.
• Patients categorized as having stroke mimic will be excluded from analysis afterwards

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ischemic Stroke; Patients presenting at emergency department / Intensive Care unit with ischemic stroke; registration of baseline clinical data; registration of baseline blood parameters (in context of standard of clinical care); additional blood sampling at 5 time points during 1st week with the purpose of full coagulation testing and cell free DNA methylation	Diagnostic test: blood sampling; At 5 time points (D0 (T0),morning after (T0B),D3 (T1),D5 (T2),D7(T3)) blood samples will be drawn next to blood sampling in context of standard of clinical care. A full coagulation and inflammation profile will be obtained as well as cell free DNA methylation
Haemorrhagic stroke; Patients presenting at emergency department / Intensive Care unit with haemorraghic stroke (spontaneous intracranial bleeding, no trauma); registration of baseline clinical data; registration of baseline blood parameters (in context of standard of clinical care); additional blood sampling at 5 time points during 1st week with the purpose of full coagulation testing and cell free DNA methylation	Diagnostic test: blood sampling; At 5 time points (D0 (T0),morning after (T0B),D3 (T1),D5 (T2),D7(T3)) blood samples will be drawn next to blood sampling in context of standard of clinical care. A full coagulation and inflammation profile will be obtained as well as cell free DNA methylation
Aneursmal Subarachnoid Haemorrhage; Patients presenting at emergency department / Intensive Care unit with aneurysmal subarachnoid haemorrhage; registration of baseline clinical data; registration of baseline blood parameters (in context of standard of clinical care); additional blood sampling at 5 time points during 1st week with the purpose of full coagulation testing and cell free DNA methylation	Diagnostic test: blood sampling; At 5 time points (D0 (T0),morning after (T0B),D3 (T1),D5 (T2),D7(T3)) blood samples will be drawn next to blood sampling in context of standard of clinical care. A full coagulation and inflammation profile will be obtained as well as cell free DNA methylation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Outcome Modified rankin scale	Modified Rankin Scale as defined by: score 0: no symptoms score 1: No significant disability despite symptoms; able to carry out all usual duties and activities Score 2:Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance Score 3: Moderate disability; requiring some help, but able to walk without assistance Score 4:Moderately severe disability; unable to walk and attend to bodily needs without assistance Score 5: Severe disability; bedridden, incontinent and requiring constant nursing care and attention Score 6:Dead With Score 3-6 defined as poor outcome and score 0-2 defined as good outcome	3 months
Functional Outcome recurrent stroke	Recurrent stroke during first 3 months	3 months
Vital Outcome - all cause mortality	Mortality rate in the participants of all cause at 3 months	3 months
Functional Outcome EuroQol-5D	EuroQol-5D questionnaire scoring different aspects of functionality In each dimension a scale of 1-5 will be recorded, defined as: mobilityNo problemsSlight problemsModerate problemsSevere problems'unable to'; self-careNo problemsSlight problemsModerate problemsSevere problems'unable to'; usual activitiesNo problemsSlight problemsModerate problemsSevere problems'unable to'; pain/discomfortNo problemsSlight problemsModerate problemsSevere problemsextreme; anxiety / depressionNo problemsSlight problemsModerate problemsSevere problemsextremely a global health score will be assessed	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU Length of stay	duration (days)	3 months
Hospital Length of stay	duration (days)	3 months
Need for mechanical ventilation in ICU	Yes/No and duration (days)	3 months
Need for renal replacement therapy in ICU	YES / NO and duration (days)	3 months
Deep vein thrombosis	Yes/No	3 months
Need for ventriculo-external drain / ventriculo-peritoneal drain	Yes / No	3 months
Rate of delayed cerebral ischemia participants with aneurysmal subarachnoid haemorrhage	Rate of delayed cerebral ischemia in participants with aneurysmal subarachnoid haemorrhage; vasospasm: clinical / radiological (transcranial doppler, CT perfusion, MRI); Delayed cerebral ischemia as diagnosed with MRI	3 months
Need for decompressive craniectomy	Yes / no	3 months
Haemorrhagic transformation of infarction	yes / No	3 months
Rebleeding aneurysm in aneurysmal subarachnoid haemorrhage	yes /no	3 months
Rate of epilepsy	Both convulsive epileptic episode as non-convulsive epileptic episode. Both clinical diagnosis and elektro-encephalogram	3 months
Rate of infection in participants	CNS infection, Pulmonary infection, genito-urinary infection, catheter related blood stream infection,gastro-intestinal infection, skin infection, other infection, bacteriemia, fungaemia	3 months
Rate of Intensive Care Aquired weakness (ICUAW)	critical illness myopathy, critical illness polyneuropathy or icu-AW	3 months
Rate of diabetes insipidus during first week	Diabetes insipidus	7days
Rate of cardiovascular compromise during first week	As defined by use of vasopressors and inotropes / acute heart failure / acute myocardial infarction / cardiac arrest / new arrythmia / use of VA-ECMO	7 days
Rate of acute respiratory failure during first week	acute respiratory failure (intubation + mechanical ventilation / non-invasive ventilation / ARDS), need for VV-ECMO / neurogenic pulmonary edema	7 days
Rate of Acute kidney injury during first week	acute kidney injury (KDIGO classification)	7 days
Rate of enteral feeding (oral/nasograstic) or Total parenteral nutrition during first week	TPN / enteral feeding (oral/nastrogastric)	7 days
Rate of Acute liver failure during first week	Acute liver failure; INR > 1.5; Any grade of hepatic encefalopathy; No prior evidence of liver disease	7 days
Rate of infection during first week	CNS infection / pulmonary infection / endocarditis / UTI / GI infection /skin infection / blood stream infection	7 days
Rate of antiplatelet / anticoagulant therapy during first week	Rate of antiplatelet therapy or anticoagulant therapy in participants	7 days

Collaborators and Investigators

• Sponsor: Ziekenhuis Oost-Limburg
• Collaborators: Synapse bv
• Investigators: Principal Investigator: Hendrik Stragier, MD, Ziekenhuis Oost-Limburg

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2023
• Primary Completion (Estimated): May 2, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: May 30, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Estimated): November 14, 2024
• Last Update Submitted That Met QC Criteria: November 12, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hematologic Diseases; Hemorrhagic Disorders; Intracranial Hemorrhages; Ischemic Stroke; Hemorrhagic Stroke; Stroke; Ischemia; Hemorrhage; Subarachnoid Hemorrhage; Hemostatic Disorders; Blood Coagulation Disorders
• Other Study ID Numbers: Z-2022142

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
• product manufactured in and exported from the U.S.: No