Condition category
Circulatory System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Background and study aims
A subarachnoid haemorrhage (SAH) is a type of stroke that is most often caused by a bulge in a brain blood vessel (aneurysm) bursting and bleeding into the subarachnoid space surrounding the brain. It is a life-threatening disease and those patients who survive the early bleeding are at risk of developing secondary complications such as delayed cerebral ischemia (DCI), a form of secondary stroke. In general, DCI is the major cause of poor outcome and death after SAH. One of the major contributors to DCI is the amount of blood in the subarachnoid space, and reducing the subarachnoid blood has been found to decrease DCI. Therefore the aim of this study is to assess the effect of blood clearance using a blood resolving agent (rt-PA) in patients with severe aneurysmal SAH.

Who can participate?
Patients aged over 18 with severe aneurysmal SAH

What does the study involve?
Participants are randomly allocated to one of two groups. One group is treated with rt-PA via a standard monitoring catheter (tube) into the brain chambers (ventricles) whilst being slowly rotated on a moving bed for 48 hours. The other group receives treatment as usual. Both groups are followed up to assess their neurological (mental) outcome and undergo CT scans to check for cerebral infarctions (brain damage).

What are the possible benefits and risks of participating?
By reducing the amount of blood in the subarachnoid space, DCI and poor neurological outcome may be prevented. One possible risk of rt-PA is an increased risk of bleeding in the brain (intracranial) or in the rest of the body (systemic). However, based on previous studies, the risk of side effects is very low.

Where is the study run from?
Heinrich-Heine University (Germany)

When is the study starting and how long is it expected to run for?
December 2008 to September 2011

Who is funding the study?
Heinrich-Heine University (Germany)

Who is the main contact?
Prof. Daniel Hänggi

Trial website

Contact information



Primary contact

Prof Daniel Hänggi


Contact details

Department of Neurosurgery
Heinrich-Heine University
Moorenstr. 5

Additional identifiers

EudraCT number number

Protocol/serial number

Study ID: 3062

Study information

Scientific title

Prospective, randomized, phase IIb trial on concomitant intraventricular fibrinolysis and low-frequency rotation after severe subarachnoid hemorrhage


Study hypothesis

To test whether increased wash-out of subarachnoid blood by intraventrikular fibrinolysis and low-frequency rotation can reduce the incidence of secondary brain injury and poor outcome after aneurysmal subarachnoid hemorrhage (SAH).

Ethics approval

Local Institutional Ethics Committee of the Medical Faculty of Heinrich-Heine University, 06/06/2008, ref: 3062

Study design

Single-center randomized controlled phase IIb study with blinded outcome analysis

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet


Aneurysmal subarchnoid hemorrhage


Concomitant intraventricular fibrinolysis (rt-PA) and low frequency rotational therapy for 48 hours, as compared to treatment as usal.

Experimental therapy consists of intraventricular application of recombinant tissue plasminogen activator (rt-PA, Actilyse®, Boehringer Ingelheim, Germany) and low frequency rotational therapy (RotoRest®, KCI, NY, USA). Experimental therapy is initiated 6 hours, after obliteration of the ruptured aneurysm and unremarkable postinterventional CT scan, and conducted for 48 hours. For intraventricular fibrinolysis, 5 mg of rt-PA will be diluted in 2ml of NaCl and given as an intraventicular bolus every 12 hours over 48 hours via the external ventricular drain. After rt-PA bolus, the external ventricular drain will be locked and solely used to monitor intracranial pressure for 30 minutes to avoid premature drainage of the fibrinolytic agent. During the 48-hour period patients will remain sedated and intubated with concomitant lateral rotational therapy. Daily CT scanning will be performed until 2 days after cessation of rt-PA fibrinolysis to rule out hemorrhagic complications. Patients will be monitored for DCI using Perfusion-CT scanning.

Intervention type



Phase II

Drug names

Primary outcome measure

Glasgow outcome score at discharge and after 6 weeks

Secondary outcome measures

1. Clot clearance rate (CCR) between day 1 and day 5 after SAH ictus
2. Radiographic vasospasm between day 1 and day 15 after SAH ictus
3. New cerebral infarction on discharge CT or after death
4. Occurrence of posthemorrhagic hydrocephalus at discharge

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Aneurysmal SAH (WFNS grade III-V)
2. Fisher grade II - IV
3. Patient age > 18
4. Admission less than 24 hours after ictus
5. No history for anticoagulative or antiaggregative agents
6. Informed consent by a legal representative

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Non-aneurysmal or Fisher ° 0-I SAH
2. Fusiform, mycotic or traumatic aneurysms
3. Pregnancy
4. Admission greater than 24 hours after ictus
5. History for severe cardiovascular disease
6. Clotting disorders
7. Platelet count less than 100,000, INR greater than 1.4
8. Ongoing internal bleeding

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Heinrich-Heine University

Sponsor information


Heinrich-Heine University (Germany)

Sponsor details

c/o Prof. Dr Daniel Hänggi
Department of Neurosurgery
Moorenstr. 5

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Heinrich-Heine-Universität Düsseldorf

Alternative name(s)

Heinrich Heine University Düsseldorf, HHU

Funding Body Type

government organisation

Funding Body Subtype

Local 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

2013 results in:

Publication citations

  1. Results

    Etminan N, Beseoglu K, Eicker SO, Turowski B, Steiger HJ, Hänggi D, Prospective, randomized, open-label phase II trial on concomitant intraventricular fibrinolysis and low-frequency rotation after severe subarachnoid hemorrhage., Stroke, 2013, 44, 8, 2162-2168, doi: 10.1161/STROKEAHA.113.001790.

Additional files

Editorial Notes

26/05/2017: Plain English summary added.