Delayed Cerebral Ischaemia and Coagulation Alterations After Aneurysmal Subarachnoid Haemorrhage

Active, not recruiting

• Conditions: Aneurysmal Subarachnoid Hemorrhage
• Interventions: Device: ROTEM; Procedure: EEG; Procedure: bilateral compression ultrasound of the lower extremity veins

• Registration Number: NCT03985176
• Lead Sponsor: Tampere University Hospital

Brief Summary

Despite the advances in neurosurgical and -radiological techniques and intensive care, the mortality and morbidity rates in SAH have not changed in recent years. There is still only a limited understanding of the mechanisms of secondary insults causing brain injury after SAH, also called delayed cerebral ischemia (DCI).

In this study, the investigators are exploring the use of quantifiable biomarkers from blood and continuous EEG monitoring as tools for the diagnostics of DCI. Additionally, the investigators are looking into other clinical variables (eg. pain, heart function) as factors of DCI.

Detailed Description

Subarachnoidal hemorrhage (SAH) is a cause of long-term disability and death. Annually about 1000 people in Finland suffer from SAH, their average age being under 50 years. SAH has a mortality rate of 12 % acutely and 40 % of patients die within a month from admission to hospital. In addition, 30 % of the surviving patients remain with neurological deficits. Most survivors of the primary insult suffer from a secondary injury during the first 2-3 weeks from the insult.

Despite the advances in neurosurgical and -radiological techniques and intensive care, the mortality and morbidity rates in SAH have not changed in recent years. There is still only a limited understanding of the mechanisms of secondary insults causing brain injury after SAH, also called delayed cerebral ischemia (DCI).

In this study, the investigators are exploring the use of quantifiable biomarkers from blood and continuous EEG monitoring as tools for the diagnostics of DCI. Additionally, the investigators are looking into other clinical variables (eg. pain, heart function) as factors of DCI.

Study Timeline

• Study First Submitted: 2019-06-05
• Study Start: 2019-06-10
• Study First Submitted QC: 2019-06-12
• Study First Posted: 2019-06-13
• Primary Completion: 2022-03-31
• Status Verified: 2022-10
• Last Update Submitted: 2022-11-07
• Last Update Posted: 2022-11-10
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 62

Inclusion Criteria

• Age ≥ 18 years
• Admitted to the Tampere University Hospital ICU due to aneurysmal SAH
• Acute subarachnoid haemorrhage (confirmed by computed tomography, CT, AND confirmed origin either with computed angiography (CTA) or digital subtraction angiography (DSA)
• Definite or approximated time for the onset of symptoms and delay to ICU admission no more than 24 hours
• Expected treatment time at least 120 hours in the Tampere University Hospital

Exclusion Criteria

• Known pregnancy
• Any long-term anticoagulant or antithrombotic medication, except for low-dose aspirin (under 150 mg/day)
• Known active cancer or cirrhotic liver disease or end-stage renal disease requiring renal replacement therapy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Aneurysmal SAH patients	bilateral compression ultrasound of the lower extremity veins	Patients suffering from aneurysmal subarachnoid haemorrhage
Aneurysmal SAH patients	ROTEM	Patients suffering from aneurysmal subarachnoid haemorrhage
Aneurysmal SAH patients	EEG	Patients suffering from aneurysmal subarachnoid haemorrhage

Primary Outcome Measures

Name	Time	Method
Incidence of delayed cerebral ischemia	14 days	Incidence of DCI (delayed cerebral ischemia)

Secondary Outcome Measures

Name	Time	Method
Assessment of cardiopulmonary function by transthoracic echocardiography	At admission and at at 24±4 hours	Function of the left and right ventricle using scale 1. hyperkinetic,2. normal, 3. moderately impaired, 4. severely impaired
Neuroglial brain injury biomarkers	From 24 to 288 hours	Peripheral blood biomarkers potentially reflecting neuroglial injury will be analysed with enzyme-linked immunosorbent assays
Maximal clot firmness of FIBTEM (FIBTEM-MCF) analysis	at 72 hours	Maximal clot firmness of FIBTEM analysis (FIBTEM-MCF) using rotational thromboelastometry (ROTEM) assay
Continuous electroencephalography	From 48 hours to 14 days	Continuous electroencephalography will be evaluated for signs that are potential surrogates of developing delayed cerebral ischemia (such as alpha-delta-ratio, focal slowing, epileptiform abnormalities, relative alpha variability)
Assessment of pain	Up to 14 days	Critical Care Pain Observation Tool values, from 0: no pain to 8: maximum pain
Incidence of deep venous thrombosis	Within 3-7 days	Incidence of deep venous thrombosis
Other rotational thromboelastometry analysis	from 24 to 288 hours	Maximal clot firmness of extrinsic (EXTEM) analysis (EXTEM-MCF) using rotational thromboelastometry
Assessment of neurological outcome	90 days	Description of the neurological outcome by using extended Glasgow Outcome Score; 1. Death; 2. Vegetative sate; 3. Lower severe disability; 4. Upper severe disability; 5. Lower moderate disability; 6. Upper moderate disability; 7. Lower good recovery; 8. Upper good recovery

Trial Locations

Locations (1)

Tampere University Hospital; 🇫🇮 Tampere, Finland