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COAgulation Disorders in Ischaemic and Haemorrhagic Stroke

Recruiting
Conditions
Haemorrhagic Stroke
Aneurysmal Subarachnoid Hemorrhage
Ischemic Stroke
Interventions
Diagnostic Test: blood sampling
Registration Number
NCT05974111
Lead Sponsor
Ziekenhuis Oost-Limburg
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
350
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Aneursmal Subarachnoid Haemorrhageblood samplingPatients 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
Haemorrhagic strokeblood samplingPatients 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
Ischemic Strokeblood samplingPatients 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
Primary Outcome Measures
NameTimeMethod
Vital Outcome - all cause mortality3 months

Mortality rate in the participants of all cause at 3 months

Functional Outcome Modified rankin scale3 months

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

Functional Outcome recurrent stroke3 months

Recurrent stroke during first 3 months

Functional Outcome EuroQol-5D3 months

EuroQol-5D questionnaire scoring different aspects of functionality

In each dimension a scale of 1-5 will be recorded, defined as:

* mobility

1. No problems

2. Slight problems

3. Moderate problems

4. Severe problems

5. 'unable to'

* self-care

1. No problems

2. Slight problems

3. Moderate problems

4. Severe problems

5. 'unable to'

* usual activities

1. No problems

2. Slight problems

3. Moderate problems

4. Severe problems

5. 'unable to'

* pain/discomfort

1. No problems

2. Slight problems

3. Moderate problems

4. Severe problems

5. extreme

* anxiety / depression

1. No problems

2. Slight problems

3. Moderate problems

4. Severe problems

5. extremely

a global health score will be assessed

Secondary Outcome Measures
NameTimeMethod
Need for ventriculo-external drain / ventriculo-peritoneal drain3 months

Yes / No

Need for renal replacement therapy in ICU3 months

YES / NO and duration (days)

Rebleeding aneurysm in aneurysmal subarachnoid haemorrhage3 months

yes /no

Rate of delayed cerebral ischemia participants with aneurysmal subarachnoid haemorrhage3 months

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

Need for decompressive craniectomy3 months

Yes / no

Rate of diabetes insipidus during first week7days

Diabetes insipidus

Hospital Length of stay3 months

duration (days)

Haemorrhagic transformation of infarction3 months

yes / No

ICU Length of stay3 months

duration (days)

Rate of epilepsy3 months

Both convulsive epileptic episode as non-convulsive epileptic episode. Both clinical diagnosis and elektro-encephalogram

Rate of infection in participants3 months

CNS infection, Pulmonary infection, genito-urinary infection, catheter related blood stream infection,gastro-intestinal infection, skin infection, other infection, bacteriemia, fungaemia

Need for mechanical ventilation in ICU3 months

Yes/No and duration (days)

Deep vein thrombosis3 months

Yes/No

Rate of Intensive Care Aquired weakness (ICUAW)3 months

critical illness myopathy, critical illness polyneuropathy or icu-AW

Rate of cardiovascular compromise during first week7 days

As defined by use of vasopressors and inotropes / acute heart failure / acute myocardial infarction / cardiac arrest / new arrythmia / use of VA-ECMO

Rate of acute respiratory failure during first week7 days

acute respiratory failure (intubation + mechanical ventilation / non-invasive ventilation / ARDS), need for VV-ECMO / neurogenic pulmonary edema

Rate of Acute kidney injury during first week7 days

acute kidney injury (KDIGO classification)

Rate of enteral feeding (oral/nasograstic) or Total parenteral nutrition during first week7 days

TPN / enteral feeding (oral/nastrogastric)

Rate of Acute liver failure during first week7 days

Acute liver failure

* INR \> 1.5

* Any grade of hepatic encefalopathy

* No prior evidence of liver disease

Rate of infection during first week7 days

CNS infection / pulmonary infection / endocarditis / UTI / GI infection /skin infection / blood stream infection

Rate of antiplatelet / anticoagulant therapy during first week7 days

Rate of antiplatelet therapy or anticoagulant therapy in participants

Trial Locations

Locations (1)

Ziekenhuis Oost-Limburg

🇧🇪

Genk, Belgium

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