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
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 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
01/12/2008
Overall trial end date
30/09/2011
Reason abandoned (if study stopped)
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
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
Basic results (scientific)
Publication list
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23735957
Publication citations
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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.