Acetazolamide as a treatment after hemorrhagic stroke

Approximately 30% of patients with subarachnoid hemorrhage (SAH) suffer from delayed cerebral ischemia (DCI). This in-hospital complication increases the risk of poor functional outcome. The only available drug that reduces the risk of DCI is nimodipine. However, the effect of nimodipine is only modest. Acetazolamide, a carbonic anhydrase inhibitor, could be a useful additional drug for the prevention of DCI by acting on 3 different pathways: (1) it increases cerebral blood flow via vasodilation, (2) it decreases brain edema through carbonic anhydrase inhibition, and (3) it decreases cerebrospinal fluid production. These combined actions of acetazolamide make it a promising drug for the prevention of DCI in patients with SAH. In a phase II study we will evaluate safety and proof-of-concept of acetazolamide in patients with aneurysmal SAH. The primary aim of this study is to evaluate whether acetazolamide improves cerebral perfusion as measured with magnetic resonance imaging (MRI) performed 7±2 days after ictus. The secondary objectives of this study are to investigate (1) the safety of acetazolamide when given until day 14 after aneurysmal SAH (aSAH), (2) whether acetazolamide improves cerebral perfusion also at day 12±2 after ictus, (3) whether the proportion of patients with DCI is lower in the intervention group. The tertiary objectives of this study are: (1) to investigate whether acetazolamide improves the Quality of Life score and modified Rankin Scale (degree of disability) at 10 weeks after SAH, and (2) to examine whether the proportion of patients with hydrocephalus is lower in the intervention group.

In a phase II study we will evaluate safety and proof-of-concept of acetazolamide in patients with aneurysmal SAH. The primary aim of this study is to evaluate whether acetazolamide improves cerebral perfusion as measured with magnetic resonance imaging (MRI) performed 7±2 days after ictus.

day 7±2 after ictus, day 12±2 after ictus, 10 weeks after ictus

In the intervention group, subjects will receive acetazolamide intravenously as well as treatment as usual. The dosage of acetazolamide will be similar to the average dosage used for the treatment of intracranial hypertension: 1.5 grams per day in three dosages of 0.5 grams in a 100 mL solution per dose. The intervention will be initiated within 72 hours after ictus, after aneurysm securing, and it will be continued until day 14 after ictus in addition to the usual treatment. The control group will not receive any study medication and will only receive treatment as usual.