Condition category
Nervous System Diseases
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status
Results overdue

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 20–40% 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 18–75 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

Trial website

Contact information



Primary contact

Dr Ronny Beer


Contact details

Neurological Intensive Care Unit
Department of Neurology
Innsbruck Medical University
Anichstrasse 35

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Novel biomarkers for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: cellular microparticles revisited


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


Secondary study design

Cohort study

Trial setting


Trial type


Patient information sheet

Not available in web format yet, please use the contact details below to request patient information material.


Aneurysmal subarachnoid hemorrhage/neurocritical care


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 1–7 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



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


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Patients of either sex aged between 18–75 years
2. Signs and symptoms of SAH with an onset within 48 hours before screening irrespective of World Federation of Neurological Surgeons (WFNS) grade (I–V) 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


Age group




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


Recruitment end date



Countries of recruitment


Trial participating centre

Neurological Intensive Care Unit

Sponsor information


Austrian Science Fund (FWF) (Austria)

Sponsor details

Haus der Forschung
Sensengasse 1
+43 (0) 1 5056740

Sponsor type




Funder type


Funder name

Austrian Science Fund (FWF) (Austria), ref: KLI-375-B00

Alternative name(s)

FWF Austrian Science Fund, Fonds zur Förderung der Wissenschaftlichen Forschung, FWF Der Wissenschaftsfonds, Der Wissenschaftsfonds FWF, FWF, FFWF

Funding Body Type

government organisation

Funding Body Subtype

National government



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

Publication citations

Additional files

Editorial Notes