Glibenclamide in Aneurysmatic Subarachnoid Hemorrhage

Subarachnoid Hemorrhage, Aneurysmal Clinical Trial

— GASH  

Official title:

Glibenclamide in Aneurysmatic Subarachnoid Hemorrhage: A Prospective and Randomized Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03569540
• Other study ID #: 55947016.2.0000.0068
• Status: Recruiting
• Phase: Phase 4
• Start date: July 3, 2018
• Est. completion date: December 1, 2019

Study information

• Verified date: January 2018
• Source: University of Sao Paulo General Hospital
• Contact: Bruno Braga Costa, MD
• Phone: +5511995429966
• Email: neurobraga[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 1, 2019
• Est. primary completion date: July 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage
• Subarachnoid Hemorrhage, Aneurysmal

Intervention

Drug:
• Glibenclamide
Placebo-controlled; Double blind test

Other:
• Placebo
Amylum

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas da Faculdade de Medicina de São Paulo	São Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Rankin Scale (early)	Evaluate patients life quality and morbidity, from 1 to 6 ('no symptoms' to 'Death')	To be measured on the 21th day of medication/control, when happens the end of intervention
Primary	Short-Form Healthy Survey Questionnaire (SF-36)	Cognitive assessment and quality of Life measured by 11 questions that leads to a quantification scale called Raw Scale (RS). The RS identify 8 domains with a calculable score from 0 (worst) to 100 (best): Functional capacity; Limitation by physical aspects; Pain; General health; Vitality; Social aspects; Emotional aspects and Mental health.	To be executed 6 months after the end of intervention
Primary	Modified Rankin Scale (late)	Evaluate patients life quality and morbidity, from 1 to 6 ('no symptoms' to 'Death')	To be measured 6 months after the end of intervention and compared with the early result