Dapsone Use in Patients With Aneurysmal Subarachnoid Hemorrhage.

Subarachnoid Hemorrhage Clinical Trial

Official title:

Neuroprotective Effect of Dapsone in Patients With Aneurysmal Subarachnoid Hemorrhage: Prospective, Randomized, Double-Blinded, Placebo-Controlled, Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05131295
• Other study ID #: 35/07
• Status: Completed
• Phase: Phase 3
• Start date: September 5, 2007
• Est. completion date: March 10, 2009

Study information

• Verified date: October 2021
• Source: El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Dapsone is a drug that has been used clinically for several decades due to its anti-infective effect, making it widely available. Its neuroprotective effects have been found through its glutamate receptors antagonistic effect. Their main objective was to study the neuroprotective properties in patients with aneurysmal subarachnoid hemorrhage and high-risk factors for the development of cerebral vasospasm. Both the placebo and the dapsone used in this clinical trial were provided by the institution's neurochemistry laboratory.

Description:

A prospective, analytical, randomized, double-blinded, placebo-controlled clinical trial was realized. Participants suffering from aneurysmal subarachnoid hemorrhage (SAH), matching the inclusion criteria, were randomly assigned using a computer-derived table to receive from admission to the 15th day post-ictus an oral dose of placebo (aluminum hydroxide suspension) or a dapsone suspension containing 100mg per day. A nasogastric tube was used in participants with unpaired consciousness. All patients underwent aneurysm clipping or obliteration employing endovascular coils. Both groups received the standard of care (which included oral nimodipine from admission until the 21st post-ictal day, normovolemia, and dextran), and if required, vasogenic amines and/or cerebral intra-arterial administration of nimodipine in cases of cerebral vasospasm.

The participants' characteristics were assessed before the randomization process in both groups. The clinical severity was classified by the World Federation of Neurological Surgeons (WNFS), and the amount of subarachnoid blood on CT was evaluated using the Fisher scale. Patients were evaluated during their stay to look for the appearance of DCI and were followed for at least three months to evaluate their clinical outcome using the modified Rankin Scale (mRS). Severe adverse events such as methemoglobinemia and other less severe effects that forced treatment discontinuation were also assessed.

Data were analyzed according to a defined prospective plan. The primary endpoint was the incidence of DCI during the first 21 days post-SAH.

The projected sample size was 50 patients, guaranteeing a power of 80% (error β 0.2) to detect a statistically significant difference between placebo and dapsone with an accepted two-tailed α error of 0.05. The sample size was calculated assuming an incidence of DCI in the placebo group of 45% and the dapsone group of 10%, making a difference of 35% between groups.

The clinical outcome at three months and the presence of infarction on CT at patient discharge were analyzed as secondary outcomes.

Categorical variable data is presented as incidences and compare groups using the χ2 test or Fisher's exact test (when any of the cells had less than five patients). Continuous variables are presented as means and standard deviation (SD). The statistical test for these variables was the Student's t-test or nonparametric tests such as the Mann-Whitney U test.

Statistical significance with a p-value <0.05 was established and the SPSS statistical package (version 23.0) was used to perform the analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 10, 2009
• Est. primary completion date: December 7, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Participants presented with aneurysmal subarachnoid hemorrhage.

• Candidates to aneurysm occlusion.

• Fisher scale grade III or IV.

Exclusion Criteria:

• Known glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• Anemia at admission.

• Known allergy to sulfones or sulfas.

• Severe systemic disease (renal or hepatic failure).

Related Conditions & MeSH terms

• Aneurysmal Subarachnoid Hemorrhage
• Brain Ischemia
• Cerebral Infarction
• Delayed Cerebral Ischemia
• Hemorrhage
• Ischemia
• Subarachnoid Hemorrhage
• Subarachnoid Hemorrhage, Aneurysmal
• Vasospasm, Cerebral
• Vasospasm, Intracranial

Intervention

Drug:
• Dapsone
Dapsone is a drug that has been used clinically for several decades due to its anti-infective effect. It has an anti-inflammatory effect due to its inhibitory action on neutrophils. Neuroprotective effects have been found experimentally with the use of dapsone, predominantly through its glutamate receptors antagonistic effect; these are the main receptors involved in neuronal excitotoxicity.
• Aluminum Hydroxide Gel
Aluminum Hydroxide Gel is an antacid that works quickly to lower the acid in the stomach

Locations

Country	Name	City	State
Mexico	El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez	Mexico City

Sponsors (1)

Lead Sponsor	Collaborator
El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Country where clinical trial is conducted

Mexico, 

References & Publications (46)

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* Note: There are 46 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of clinically defined delayed cerebral ischemia	Development of focal neurological deficits or impaired consciousness with progression to stupor or coma, not explained by any other medical condition.	During the first 21 days post-ictus.
Secondary	Clinical outcome at discharge and three months later	Evaluation of the clinical outcome using the modified Rankin Scale at discharge and three months follow up. Considering a cutoff point defined as favorable if lower or equal to 2 and an unfavorable if greater or equal to 3.	An average of 12 days after hospitalization and at three months follow up after discharge.
Secondary	Infarction incidence demonstrated by computerized tomography (CT).	Appearance of a new localized hypodensity in a vascular distribution in the final CT prior to discharge, using validated arterial territory maps.	An average of 12 days after hospitalization.