BA&UK: Brain Aneurysms: Utility of Cisternal Urokinase Irrigation

Sponsor

University of Valencia (Other)

Overall Status

Completed

CT.gov ID

NCT04792944

Collaborator

(none)

247

Enrollment

Location

168

Actual Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Subarachnoid Hemorrhage, Aneurysmal Vasospasm, Cerebral Hydrocephalus	Drug: Urokinase Procedure: Endovascular treatment Procedure: Clipping Procedure: External ventricular drain

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.

Study Design

Study Type:

Observational

Actual Enrollment :

247 participants

Observational Model:

Other

Time Perspective:

Retrospective

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

Actual Study Start Date :

Jan 1, 2007

Actual Primary Completion Date :

Dec 31, 2020

Actual Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
No treatment Those are the patients that do not receive any treatment for the aneurysm, neither endovascular nor surgical
External ventricular drain only with neither embolization nor clipping These patients will be treated with an external ventricular drain only with neither embolization nor clipping	Procedure: External ventricular drain Insertion of an external ventricular drain to treat acute hydrocephalus
Embolization These patients will be treated endovascularly	Procedure: Endovascular treatment Aneurysm treatment through endovascular methods
Programmed surgical clipping These patients will be treated no on an emergency basis with surgical clipping of an aneurysm that has bled	Procedure: Clipping Surgical clipping of brain aneurysms
Emergency surgical clipping with cisternal urokinase administration These patients with undergo emergency surgical clipping with cisternal urokinase administration	Drug: Urokinase Washing the subarachnoid clot induced by a subarachnoid haemorrhage aneurysmal bleeding with urokinase after aneurysm clipping Other Names: Aneurysm clipping plus cisternal lavage with Urokinase Procedure: Clipping Surgical clipping of brain aneurysms
Patients with incidental brain aneurysm discovery with no SAH and programmed aneurysm clipping This group will include patients with incidental brain aneurysm discovery with no SAH and programmed aneurysm clipping	Procedure: Clipping Surgical clipping of brain aneurysms

Outcome Measures

Primary Outcome Measures

Vasospasm [21 days]
Presence and severity of vasospasm
Cerebrospinal fluid diversion [1 year]
Need for temporary or definitive cerebrospinal fluid diversion
Mortality rate [1 year]
Mortality rate in each group of patients
Outcome [1 year]
Glasgow Outcome Score (GOSE) at discharge, 6 and 12 months posttreatment

Secondary Outcome Measures

Aneurysm regrowth [10 years]
Aneurysm regrowth on follow-up after each tipe of treatment
Aneurysm rebleed [10 years]
Aneurysm rebleed on follow-up after each tipe of treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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