Brain Aneurysms: Utility of Cisternal Urokinase Irrigation

Completed

• Conditions: Subarachnoid Hemorrhage, Aneurysmal; Vasospasm, Cerebral; Hydrocephalus
• Interventions: Procedure: Endovascular treatment; Procedure: External ventricular drain; Procedure: Clipping; Drug: Urokinase

• Registration Number: NCT04792944
• Lead Sponsor: University of Valencia

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.

Study Timeline

• Study Start: 2007-01-01
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Status Verified: 2021-03
• Study First Submitted: 2021-03-07
• Study First Submitted QC: 2021-03-07
• Last Update Submitted: 2021-03-07
• Study First Posted: 2021-03-11
• Last Update Posted: 2021-03-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 247

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Embolization	Endovascular treatment	These patients will be treated endovascularly
External ventricular drain only with neither embolization nor clipping	External ventricular drain	These patients will be treated with an external ventricular drain only with neither embolization nor clipping
Programmed surgical clipping	Clipping	These patients will be treated no on an emergency basis with surgical clipping of an aneurysm that has bled
Emergency surgical clipping with cisternal urokinase administration	Clipping	These patients with undergo emergency surgical clipping with cisternal urokinase administration
Patients with incidental brain aneurysm discovery with no SAH and programmed aneurysm clipping	Clipping	This group will include patients with incidental brain aneurysm discovery with no SAH and programmed aneurysm clipping
Emergency surgical clipping with cisternal urokinase administration	Urokinase	These patients with undergo emergency surgical clipping with cisternal urokinase administration

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Aneurysm rebleed	10 years	Aneurysm rebleed on follow-up after each tipe of treatment
Aneurysm regrowth	10 years	Aneurysm regrowth on follow-up after each tipe of treatment

Trial Locations

Locations (1)

Hospital General Universitario de Valencia; 🇪🇸 Valencia, Spain