Neuroprotective Effect of Dapsone in Patients With Aneurysmal Subarachnoid Hemorrhage: Prospective, Randomized, Double-Blinded, Placebo-Controlled, Clinical Trial
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Incidence of clinically defined delayed cerebral ischemia
Study Overview
Brief 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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
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).
Arms & Interventions
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.
Intervention: Dapsone (Drug)
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.
Intervention: Aluminum Hydroxide Gel (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Clinical outcome at discharge and three months later(An average of 12 days after hospitalization and at three months follow up after discharge.)
- Infarction incidence demonstrated by computerized tomography (CT).(An average of 12 days after hospitalization.)