Glibenclamide in Aneurysmatic Subarachnoid Hemorrhage
Glibenclamide in Aneurysmatic Subarachnoid Hemorrhage
A randomized, double-blind and prospective trial meant to evaluate the use of Glibenclamide
 on acute aneurysmatic subarachnoid hemorrhage. Patients will allocated randomly in two
 groups, one for 05 mg daily intake of glibenclamide for 21 days and another for control with
 placebo. General clinical data and late cognitive status will be accessed in both groups.
GASH is a double blind, prospective and randomized clinical trial centered on the University
 of Sao Paulo General Hospital. Patients will be recruited from neurological/neurosurgical
 intensive care units. Appropriate ethics and regulatory approvals will be sought for all
 subjects, according to the International Conference on Harmonization guidelines for good
 clinical practice (ICH GCP). Investigators will obtain informed written consent from all
 patients or their legal representative. Recruitment will take place between 2018 and 2019.

 Patients will be randomly assigned (1:1) to receive either glibenclamide 5mg or placebo.
 Coded boxes containing either 21 similar tablets of glibenclamide 5mg or placebo will be
 assigned a number. A computer-generated randomization code will be used to randomize patients
 by blocks of ten (five glibenclamide, five placebo). Each box will be identified by a code
 number specific and subsequently selected for distribution in ascending numerical order.
 Patients will start treatment as soon as possible within 96 h of the ictus, with a daily dose
 till the 21° day after the bleed. Trial medication consisted of one tablet a day, given
 orally or via a nasogastric tube. Aneurysm treatment, either by microsurgery or embolization,
 will be performed as soon as possible, according with the standard of care for the recruiting
 center. Nimodipine 60mg, every four hours, will be started on admission and continued till
 the 21° day after the ictus, in all patients as standard of care.

 Patient's demographics, medical history and relevant investigation results will be collected.
 The severity of the hemorrhage will be clinically assessed by World Federation of
 Neurosurgical Societies grading scale and radiologically using the modified Fischer scale. At
 6 months of follow up patients will be interviewed with modified Rankin scale (mRS)
 questionnaire (a scale that measures degree of incapacity/ dependence and mortality after
 neurological events) by a nurse or a physician with no knowledge of treatment allocation.
 Psychologists will evaluate quality of life and cognitive performance using the "short-form
 health survey questionnaire" (SF-36) and neuropsychological tests. The main hypothesis is
 that, once compared with standard of care, glibenclamide 5mg will provide better clinical
 outcome and additionally will decrease mortality and improve quality of life and cognitive
 performance after 6 months.

 Sample size: It was estimated the sample size of 50 randomized patients to give 90% power at
 the 5% significance level (two-sided) to detect a treatment effect equivalent to an absolute
 increase of 7% in the proportion of patients with a favorable outcome (30-day mortality rate
 after subarachnoid hemorrhage approaches 50% and 25% of survivors present some degree of
 neurological morbidity25). This calculation was based on an ordinal analysis of the 6-month
 mRS (the primary outcome) assuming that the treatment effect follows a proportional odds
 model.
Inclusion Criteria:

 -  Radiological confirmatory evidence of an aneurysmal subarachnoid hemorrhage (by
 digital subtraction angiography, CT angiography, or magnetic resonance angiography)

 -  Presentation less than 96 h from ictus

 Exclusion Criteria:

 -  Patients taking glibenclamide therapy at presentation

 -  Pregnancy

 -  Hunt & Hess V

 -  Known renal or hepatic impairment

 -  Patient not fully independent before bleed,

 -  Strong suspicion of drug or alcohol misuse

 -  Patient taking warfarin-type drugs

 -  Suspected additional life-threatening disease