Dapsone Use in Patients With Aneurysmal Subarachnoid Hemorrhage.

November 10, 2021 updated by: El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • Mexico City, Mexico, 14269
        • El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Dapsone
Besides the standard of care, those assigned to the dapsone group received orally 100mg (2.5 ml) of dapsone suspension daily, from the admission day until the 15th-day post-ictus.
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.
PLACEBO_COMPARATOR: Placebo
Besides the standard of care, those assigned to the placebo group received orally 2.5 ml of aluminum hydroxide gel daily, from the admission day until the 15th-day post-ictus.
Drug: Aluminum Hydroxide Gel
Aluminum Hydroxide Gel is an antacid that works quickly to lower the acid in the stomach

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of clinically defined delayed cerebral ischemia
Time Frame: During the first 21 days post-ictus.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical outcome at discharge and three months later
Time Frame: An average of 12 days after hospitalization and at three months follow up after discharge.
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.
Infarction incidence demonstrated by computerized tomography (CT).
Time Frame: An average of 12 days after hospitalization.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Investigators

  • Principal Investigator: Edgar Nathal, MD, El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 5, 2007

Primary Completion (ACTUAL)

December 7, 2008

Study Completion (ACTUAL)

March 10, 2009

Study Registration Dates

First Submitted

October 29, 2021

First Submitted That Met QC Criteria

November 10, 2021

First Posted (ACTUAL)

November 23, 2021

Study Record Updates

Last Update Posted (ACTUAL)

November 23, 2021

Last Update Submitted That Met QC Criteria

November 10, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 35/07

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No IPD plan to protect the participants' identity.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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