Plain English Summary
Background and study aims
Spontaneous subarachnoid haemorrhage (bleeding on the surface of the brain ) accounts for about 5% of all cases of stroke. Although the initial death rate has been reducing over the past two decades, long-term outcomes still remain disappointing because of many complications in the course of the disease despite best intensive care. Delayed cerebral ischemia (insufficient blood flow to the brain) is a common complication and occurs in about 2040% of patients and may progress to cerebral infarction (blockage of blood vessels). The causes of this serious complication remain poorly understood. While traditionally attributed to the narrowing of large brain vessels (referred to as vasospasm), recent research has indicated that delayed cerebral ischemia may instead result from many factors. Recently, small membrane fragments, called cellular microparticles, have been identified as players in these mechanisms. In a small-scale study, our research group was able to detect increased cellular microparticle release into the blood circulation in patients with subarachnoid hemorrhage. Further, we found a strong correlation with the occurrence of delayed ischemic complications. Therefore, we propose that the generation of cellular microparticles is due to dysfunction of blood vessels after subarachnoid hemorrhage, and has an impact on the occurrence of delayed cerebral ischemia. Changes in the load of cellular microparticles may happen before delayed cerebral ischemia and detection of these abnormalities can help to identify patients at risk.
Who can participate?
Men and women aged between 1875 years with signs and symptoms of a subarachnoid hemorrhage that started within 48 hours before screening.
What does the study involve?
In this study we will find out the changes in cellular microparticle load by flow cytometry, an established cell counting and characterization method, in the blood circulation. We will perform an array of statistical tests and delayed cerebral ischemia is assessed by magnetic resonance imaging according to a standardized procedure. Functional outcome is assessed with a set of tests 3 months later.
What are the possible benefits and risks of participating?
Participation of the patients in this study will not interfere with their usual standard of care, and therefore patients may not directly benefit from this study themselves. However, their participation may help others who find themselves in the same position in the future. Frequent collections of blood and cerebrospinal fluid samples are necessary to guide intensive care treatment of patients suffering from subarachnoid hemorrhage. We believe that the additional withdrawal of 5-15 ml of blood per sampling required for our analyses poses no extra risk for our patients. On the other hand, a clear benefit for all patients is the regular follow-up with standardized tests.
Where is the study run from?
The Center for Neurology and Neurosurgery of Innsbruck Medical University (Austria).
When is the study starting and how long is it expected to run for?
Recruitment starts in June 2014. The study will run for 36 months.
Who is funding the study?
Austrian Science Fund (FWF), Austria.
Who is the main contact?
Dr Ronny Beer
ronny.beer@i-med.ac.at
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
KLI-375-B00
Study information
Scientific title
Novel biomarkers for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: cellular microparticles revisited
Acronym
Study hypothesis
It is hypothesised that the generation of cellular microparticles is a consequence of the microvascular dysfunction after subarachnoid hemorrhage, and has an impact on the occurrence of delayed cerebral ischemia. Further, it is hypothesized that changes in microparticle burden precede the emergence of delayed cerebral ischemia and detection of these abnormalities can help to identify patients at risk.
Ethics approval
Institutional Review Board of Innsbruck Medical University (Austria); 28/02/2014; ref. AN4091 292/4.6 (3328a)
Study design
Prospective observational cohort study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Other
Trial type
Screening
Patient information sheet
Not available in web format yet, please use the contact details below to request patient information material.
Condition
Aneurysmal subarachnoid hemorrhage/neurocritical care
Intervention
Objective 1 will be to examine by flow cytometry the temporal evolution of endothelial, platelet-, leukocyte-, and erythrocyte-derived microparticles in patients with aneurysmal subarachnoid hemorrhage and control patients in the systemic circulation, and where applicable in the cerebrospinal fluid (drawn from external ventricular drainage catheter) and in blood drawn from the internal jugular vein, as well as intracranial arteries if it is necessary to advance the microcatheter distally during angiography. Sampling of body fluids is performed at predefined, standardized time-points (i.e., daily from treatment days 17 and every other day thereafter until treatment day 14, and at treatment day 21).
Objective 2 will investigate the clinical course and outcome of the study cohort focusing on the occurrence of cerebral vasospasm and delayed cerebral ischemia. Therefore, clinical and neuroimaging investigations follow a stringent time-dependent protocol (neurological assessments will be completed every 6 hours or upon evident clinical deterioration from admission until day 21; neuroimaging studies will be performed at admission [baseline] to confirm the diagnosis, after aneurysm repair [i.e., within 24 hours], at day 8 ± 2, day 14 ± 2, day 21 ± 2 and day 90 ± 7; additional neuroimaging studies indicated at the discretion of the treating physicians are permitted). All patients will be followed for at least 3 months.
Objective 3 will correlate the potential qualitative and quantitative changes in cellular microparticle load with the occurrence of cerebral vasospasm and/or delayed cerebral ischemia, as well as with functional outcome assessed 3 months after the ictus.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
Prognostic value of cellular microparticles for the occurrence of cerebral infarction attributable to delayed cerebral ischemia (i.e., not adjudicated to lesions arising from the aneurysm repair procedure, intracerebral hemorrhage or ventricular drain encephalomalacia) assessed by magnetic resonance imaging (MRI) at day 21 ± 2.
Secondary outcome measures
Association of cellular microparticles with patient morbidity and mortality at the 3-month follow-up visit. Other (exploratory) endopoints, derived from the clinical database, might be analyzed on data-driven considerations.
Overall trial start date
01/06/2014
Overall trial end date
31/05/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients of either sex aged between 1875 years
2. Signs and symptoms of SAH with an onset within 48 hours before screening irrespective of World Federation of Neurological Surgeons (WFNS) grade (IV) at admission
3. A computed tomography (CT) scan shows an aneurysmal bleeding pattern in combination with the presence of an appropriate aneurysm at CT angiography or digital subtraction angiography (DSA)
4. Women of childbearing potential must have a negative serum pregnancy test
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
63 patients are required (per protocol)
Participant exclusion criteria
1. Definite contraindication to magnetic resonance imaging (MRI) (e.g., pacemakers)
2. History of trauma, cerebral vascular malformation or other non-aneurysmal source of bleeding
3. Moderate to severe cerebral vasospasm at screening
4. Known coagulopathies, long-term therapy with platelet aggregation inhibitors or oral anticoagulants
5. Severe concomitant diseases as well as patients in whom death seems imminent
Recruitment start date
01/06/2014
Recruitment end date
31/05/2017
Locations
Countries of recruitment
Austria
Trial participating centre
Neurological Intensive Care Unit
Innsbruck
6020
Austria
Sponsor information
Organisation
Austrian Science Fund (FWF) (Austria)
Sponsor details
Haus der Forschung
Sensengasse 1
Vienna
1090
Austria
+43 (0) 1 5056740
office@fwf.ac.at
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Austrian Science Fund (FWF) (Austria), ref: KLI-375-B00
Alternative name(s)
Fonds zur Förderung der Wissenschaftlichen Forschung, FWF Der Wissenschaftsfonds, FWF Austrian Science Fund, FWF, FFWF
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Austria
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list