Clinical trial NCT04792944: Brain Aneurysms: Utility of Cisternal Urokinase Irrigation
Official title: Cerebral Aneurysms: a Retrospective Study on the Experience in Our Hospital With a Comparative Analysis Between the Different Techniques Used in Its Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Vasospasm, Cerebral
Hydrocephalus
Keywords: Aneurysm
Subarachnoid haemorrhage
Fibrinolytic Therapy
Intracisternal fibrinolysis
Cerebral vasospasm
Delayed ischemic neurological deficit
Lead sponsor: University of Valencia
Sponsor class: OTHER
First posted: 2021-03-11
Enrollment: 247
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a retrospective study of all brain aneurysms treated in our Hospital since 2007

Brief summary: Despite the efforts made in its treatment, aneurysmal subarachnoid haemorrhage continues to induce high mortality and morbidity rates. Today there are treatment protocols in all hospitals. The vast majority prefer, whenever possible, the endovascular route, given its lesser aggressiveness and morbidity.

Although embolization prevents aneurysm' rebleeding, it does remove the subarachnoid blood clot. Therefore, it does not modify the evolution, incidence and severity of vasospasm.

The idea is to carry out a 10-year retrospective study classifying patients into five groups based on the type of treatment received, analyzing the results' differences. The aim is to improve what is done as much as possible and to be able to propose potential areas for improvement. Besides, this study will be the basis of a future prospective study, prepared without the current one's biases and errors.

Detailed description: Aneurysmal subarachnoid hemorrhage continues to have very high morbidity and mortality rates, despite the years elapsed and repeated attempts to reduce it.

Stabilizing the aneurysm by embolization or surgical clipping leaves unresolved the vasospasm, responsible for ischemic brain damage, causing neurological sequelae and cognitive impairment.

It has long been known that the deoxyhemoglobin liberated from the extravasated red blood cells retained in the subarachnoid clot is the leading cause of vasospasm. Different routes have been tried to minimize its deleterious effects, such as copious lavage of the skull base cisterns, lysing the subarachnoid clot with urokinase or rtPA, administration of vitamin C, iron chelators, or superoxydodismutase-like drugs.

The volume of subarachnoid hemorrhage was soon correlated with the vasospasm severity. Once this fact was known in the 1980s and 1990s, cisternal lavage was used extensively during aneurysms' surgical clipping. Clots located in the subarachnoid space were lysed with urokinase or rtPA (recombinant tissue plasminogen activator), showing positive effects, particularly evident for the most severe bleeds, those with Fisher's grades of 3 or higher.

However, the introduction of embolization changed the treatment paradigm. As the craniotomy is not carried out, the cisterns are not usually washed, which controls the rebleeding but not the vasospasm. To date, we are not aware of any study that compares the effect on vasospasm of embolization versus clipping of aneurysms with lavage of the cisterns using thrombolytic agents.

In the Neurosurgery Department of our Hospital, two periods can be identified in which the treatment of brain aneurysms has been carried out differently. In the first period between 2007 and 2011, the aneurysms were primarily subjected to embolization, and only if there was no indication for endovascular treatment, surgical clipping was performed. In the second period, between 2012 and 2018, they were operated on an emergency basis with clip application and the skull base cisterns washed with urokinase. Embolization was considered if the surgical clipping was judged too risky.

The aim is to analyze these two periods and compare the mortality, morbidity, and vasospasm rates, the need for a cerebrospinal fluid diversion (temporary and definitive), and the final neurological and cognitive status for the different therapeutic approaches.

Eligibility criteria: Inclusion Criteria:

* \>18 years of age
* harbour one or more saccular brain aneurysms
* with or without subarachnoid hemorrhage (SAH)
* multiple aneurysms

Exclusion Criteria:

* absence of brain fusiform, traumatic or mycotic aneurysms
* SAH due to other causes (trauma, anticoagulation, antiplatelet medication, arteriovenous malformation, or tumor)
* any medical, neurological, or psychiatric condition that would impair patient's evaluation
* past medical history of bleeding disorders or liver diseases altering the coagulation
* anticoagulation
* platelet count \<10x109/L
* prothrombin time \>15 seconds

Primary outcomes:
measure: Vasospasm
timeFrame: 21 days
measure: Cerebrospinal fluid diversion
timeFrame: 1 year
measure: Mortality rate
timeFrame: 1 year
measure: Outcome
timeFrame: 1 year
Secondary outcomes:
measure: Aneurysm regrowth
timeFrame: 10 years
measure: Aneurysm rebleed
timeFrame: 10 years
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
Study officials:
affiliation: Hospital General Universitario Valencia
name: Teresa V Moratal, Nurse
role: STUDY_CHAIR
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