Brain Aneurysms: Utility of Cisternal Urokinase Irrigation

NCT04792944 | Completed DMC

• 1 other identifier: CEIm 17-07-2019
• Study Type: observational
• Target: 247
• Locations: 1 country
• Sites: 1

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.

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Vasospasm, Cerebral; Hydrocephalus

Keywords

Aneurysm; Subarachnoid haemorrhage; Fibrinolytic Therapy; Intracisternal fibrinolysis; Cerebral vasospasm; Delayed ischemic neurological deficit

Outcome Measures

Primary Outcomes (4)

• Vasospasm

  Presence and severity of vasospasm

  21 days

• Cerebrospinal fluid diversion

  Need for temporary or definitive cerebrospinal fluid diversion

  1 year

• Mortality rate

  Mortality rate in each group of patients

  1 year

• Outcome

  Glasgow Outcome Score (GOSE) at discharge, 6 and 12 months posttreatment

  1 year

Secondary Outcomes (2)

• Aneurysm regrowth

  10 years

• Aneurysm rebleed

  10 years

Study Arms (6)

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

Embolization

These patients will be treated endovascularly

Procedure: Endovascular treatment

Programmed surgical clipping

These patients will be treated no on an emergency basis with surgical clipping of an aneurysm that has bled

Procedure: Clipping

Emergency surgical clipping with cisternal urokinase administration

These patients with undergo emergency surgical clipping with cisternal urokinase administration

Drug: Urokinase; Procedure: Clipping

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

Interventions

Urokinase DRUG

Washing the subarachnoid clot induced by a subarachnoid haemorrhage aneurysmal bleeding with urokinase after aneurysm clipping

Also known as: Aneurysm clipping plus cisternal lavage with Urokinase

Emergency surgical clipping with cisternal urokinase administration

Endovascular treatment PROCEDURE

Aneurysm treatment through endovascular methods

Embolization

Clipping PROCEDURE

Surgical clipping of brain aneurysms

Emergency surgical clipping with cisternal urokinase administration; Patients with incidental brain aneurysm discovery with no SAH and programmed aneurysm clipping; Programmed surgical clipping

External ventricular drain PROCEDURE

Insertion of an external ventricular drain to treat acute hydrocephalus

External ventricular drain only with neither embolization nor clipping

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is a retrospective study of all brain aneurysms treated in our Hospital since 2007

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Valencia: lead

Study Sites (1)

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Related Publications (25)

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  PMID: 29801906 RESULT

• Arakawa Y, Kikuta K, Hojo M, Goto Y, Yamagata S, Nozaki K, Hashimoto N. Milrinone reduces cerebral vasospasm after subarachnoid hemorrhage of WFNS grade IV or V. Neurol Med Chir (Tokyo). 2004 Aug;44(8):393-400; discussion 401. doi: 10.2176/nmc.44.393.

  PMID: 15508346 RESULT

• Arthur AS, Fergus AH, Lanzino G, Mathys J, Kassell NF, Lee KS. Systemic administration of the iron chelator deferiprone attenuates subarachnoid hemorrhage-induced cerebral vasospasm in the rabbit. Neurosurgery. 1997 Dec;41(6):1385-91; discussion 1391-2. doi: 10.1097/00006123-199712000-00028.

  PMID: 9402590 RESULT

• Asano T. Oxyhemoglobin as the principal cause of cerebral vasospasm: a holistic view of its actions. Crit Rev Neurosurg. 1999 Sep 24;9(5):303-318. doi: 10.1007/s003290050147.

  PMID: 10525849 RESULT

• Ayer RE, Zhang JH. Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm. Acta Neurochir Suppl. 2008;104:33-41. doi: 10.1007/978-3-211-75718-5_7.

  PMID: 18456995 RESULT

• Barbosa MD, Arthur AS, Louis RH, MacDonald T, Polin RS, Gazak C, Kassell NF. The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage. Neurosurgery. 2001 Nov;49(5):1205-12; discussion 1212-3. doi: 10.1097/00006123-200111000-00032.

  PMID: 11846914 RESULT

• Bilginer B, Onal MB, Narin F, Soylemezoglu F, Ziyal IM, Ozgen T. The effects of intravenous cilostazol and nimodipine on cerebral vasospasm after subarachnoid hemorrhage in an experimental rabbit model. Turk Neurosurg. 2009 Oct;19(4):374-9.

  PMID: 19847758 RESULT

• Dalbayrak S, Altas M, Arslan R. The effects of timing of aneurysm surgery on vasospasm and mortality in patients with subarachnoid hemorrhage. Acta Neurol Belg. 2011 Dec;111(4):317-20.

  PMID: 22368972 RESULT

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  PMID: 23328469 RESULT

• Dorhout Mees SM, Molyneux AJ, Kerr RS, Algra A, Rinkel GJ. Timing of aneurysm treatment after subarachnoid hemorrhage: relationship with delayed cerebral ischemia and poor outcome. Stroke. 2012 Aug;43(8):2126-9. doi: 10.1161/STROKEAHA.111.639690. Epub 2012 Jun 14.

  PMID: 22700527 RESULT

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  PMID: 8559330 RESULT

• Gorski R, Zabek M, Jarmuzek P. Influence of intraoperative using of recombinant tissue plasminogen activator on the development of cerebral angiospasm after subarachnoid haemorrhage in patients with ruptured intracranial aneurysms. Neurol Neurochir Pol. 2000;34(6 Suppl):41-7.

  PMID: 11452854 RESULT

• Hamada J, Mizuno T, Kai Y, Morioka M, Ushio Y. Microcatheter intrathecal urokinase infusion into cisterna magna for prevention of cerebral vasospasm: preliminary report. Stroke. 2000 Sep;31(9):2141-8. doi: 10.1161/01.str.31.9.2141.

  PMID: 10978043 RESULT

• Handa Y, Kaneko M, Takeuchi H, Tsuchida A, Kobayashi H, Kubota T. Effect of an antioxidant, ebselen, on development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates. Surg Neurol. 2000 Apr;53(4):323-9. doi: 10.1016/s0090-3019(00)00168-3.

  PMID: 10825515 RESULT

• Hanggi D, Steiger HJ. The influence of cisternal and ventricular lavage on cerebral vasospasm in patients suffering from subarachnoid hemorrhage: analysis of effectiveness. Acta Neurochir Suppl. 2011;110(Pt 2):95-8. doi: 10.1007/978-3-7091-0356-2_17.

  PMID: 21125452 RESULT

• Hirashima Y, Endo S, Horie Y, Kurimoto M. Indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage. Br J Neurosurg. 1996 Oct;10(5):477-81. doi: 10.1080/02688699647113.

  PMID: 8922707 RESULT

• Hosoda K, Fujita S, Kawaguchi T, Shose Y, Hamano S, Iwakura M. Effect of clot removal and surgical manipulation on regional cerebral blood flow and delayed vasospasm in early aneurysm surgery for subarachnoid hemorrhage. Surg Neurol. 1999 Jan;51(1):81-8. doi: 10.1016/s0090-3019(97)00508-9.

  PMID: 9952128 RESULT

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  PMID: 2295920 RESULT

• Jito J, Nakasu Y, Nakasu S, Hatsuda N, Matsuda M. Tissue plasminogen activator levels after single intracisternal injection in patients with subarachnoid hemorrhage. Neurol Med Chir (Tokyo). 2004 Feb;44(2):55-60; discussion 60. doi: 10.2176/nmc.44.55.

  PMID: 15018324 RESULT

• Kajimoto Y, Ohta T, Kuroiwa T. Comparison of intrathecally administered urokinase, tissue-type plasminogen activator, and combination of urokinase and lysine-plasminogen for clot lysis after experimental subarachnoid hemorrhage in dogs. Neurosurgery. 1997 Mar;40(3):572-7. doi: 10.1097/00006123-199703000-00029.

  PMID: 9055298 RESULT

• Kawakami M, Kodama N, Toda N. Suppression of the cerebral vasospastic actions of oxyhemoglobin by ascorbic acid. Neurosurgery. 1991 Jan;28(1):33-9; discussion 39-40. doi: 10.1097/00006123-199101000-00006.

  PMID: 1704491 RESULT

• Kodama N, Matsumoto M, Sasaki T, Konno Y, Sato T. Cisternal irrigation therapy with urokinase and ascorbic acid for prevention of vasospasm. Acta Neurochir Suppl. 2001;77:171-4. doi: 10.1007/978-3-7091-6232-3_36. No abstract available.

  PMID: 11563280 RESULT

• Li YH, Guo K, Zi XH, Song Z. [Combining exchange of cerebrospinal fluid with small dose of urokinase injection for subarachnoid hemorrhage]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2005 Apr;30(2):217-20. Chinese.

  PMID: 15898439 RESULT

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  PMID: 1866764 RESULT

• De BP, Rosenberg JB, Selvan N, Wilson I, Yusufzai N, Greco A, Kaminsky SM, Heier LA, Ricart Arbona RJ, Miranda IC, Monette S, Nair A, Khanna R, Crystal RG, Sondhi D. Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease. Hum Gene Ther. 2023 Sep;34(17-18):905-916. doi: 10.1089/hum.2023.067.

  PMID: 37624739 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial; Hydrocephalus; Aneurysm

Interventions

Urokinase-Type Plasminogen Activator

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Teresa V Moratal, Nurse

  Hospital General Universitario Valencia

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2021
• First Posted: March 11, 2021
• Study Start: January 1, 2007
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: March 11, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)