Condition category
Circulatory System
Date applied
18/07/2012
Date assigned
03/09/2012
Last edited
26/05/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

Type

Scientific

Primary contact

Prof Daniel Hänggi

ORCID ID

Contact details

Department of Neurosurgery
Heinrich-Heine University
Moorenstr. 5
Düsseldorf
40225
Germany

Additional identifiers

EudraCT number

ClinicalTrials.gov 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

Acronym

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

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Aneurysmal subarchnoid hemorrhage

Intervention

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

Other

Phase

Phase II

Drug names

Primary outcome measures

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

01/12/2008

Overall trial end date

30/09/2011

Reason abandoned

Eligibility

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

Patient

Age group

Adult

Gender

Both

Target number of participants

60

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

01/12/2008

Recruitment end date

30/09/2011

Locations

Countries of recruitment

Germany

Trial participating centre

Heinrich-Heine University
Düsseldorf
40225
Germany

Sponsor information

Organisation

Heinrich-Heine University (Germany)

Sponsor details

c/o Prof. Dr Daniel Hänggi
Department of Neurosurgery
Moorenstr. 5
Düsseldorf
40225
Germany

Sponsor type

Hospital/treatment centre

Website

http://www.uni-duesseldorf.de/

Funders

Funder type

University/education

Funder name

Heinrich-Heine-Universität Düsseldorf

Alternative name(s)

Heinrich Heine University Düsseldorf, HHU

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

Germany

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

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23735957

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.