Delayed Cerebral Ischaemia and Coagulation Alterations After Aneurysmal Subarachnoid Haemorrhage

Delayed Cerebral Ischaemia and Coagulation Alterations After Aneurysmal Subarachnoid Haemorrhage: a Clinical Observational Trial

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 Overview

• Status: Active, not recruiting
• Conditions: Aneurysmal Subarachnoid Hemorrhage
• Intervention / Treatment: Device: ROTEM; Procedure: EEG; Procedure: bilateral compression ultrasound of the lower extremity veins

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 Type: Observational
• Enrollment (Actual): 62

Contacts and Locations

Study Locations

• Finland
  • Tampere, Finland, 33500
    • Tampere University Hospital

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

Patients suffering from aneurysmal subarachnoid haemorrhage

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Aneurysmal SAH patients; Patients suffering from aneurysmal subarachnoid haemorrhage	Device: ROTEM; ROTEM measurements 24,48, 72, 120, 192 and 288 hours from aneurysmal SAH; Procedure: EEG; Continuous EEG-monitoring after aneurysm treatment until patient transferred to ward or up to 14 days after aneurysmal SAH; Procedure: bilateral compression ultrasound of the lower extremity veins; to exclude asymptomatic deep venous thrombosis once over days 3 to 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of delayed cerebral ischemia	Incidence of DCI (delayed cerebral ischemia)	14 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Investigators: Study Chair: Simo Varila, Tampere University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 10, 2019
• Primary Completion (ACTUAL): March 31, 2022
• Study Completion (ANTICIPATED): December 31, 2025

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (ACTUAL): June 13, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 10, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Intensive Care Unit; Neurosurgery; delayed cerebral ischemia; aneurysmal subarachnoid hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infarction; Stroke; Brain Infarction; Intracranial Hemorrhages; Brain Ischemia; Ischemia; Hemorrhage; Cerebral Infarction; Subarachnoid Hemorrhage
• Other Study ID Numbers: R18110

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