The effective reduction of delayed
cerebral ischemia (DCI), a main contributor for poor outcome following
aneurysmal subarachnoid hemorrhage (SAH), remains challenging. Previous clinical trials on systemic pharmaceutical treatment of SAH mostly failed to improve outcome, probably because of insensitive pharmaceutical targets and outcome measures, small sample size, insufficient subarachnoid drug concentrations and also detrimental, systemic effects of the experimental treatment per se. Interestingly, in studies that are more recent, intrathecal administration of
nicardipine pellets following surgical
aneurysm repair was suggested to have a beneficial effect on DCI and neurological outcome. However, this positive effect remained restricted to patients who were treated surgically for a
ruptured aneurysm. Because of the favorable results of the preclinical data on DCI and neurological outcome in the absence of neurotoxicity or systemic side effects, we are initiating clinical trials. The PROMISE (Prolonged Release
nimOdipine MIcro particles after
Subarachnoid hemorrhage) trial is designed as an unblinded, nonrandomized, single-center, single-dose, dose-escalation safety and tolerability phase 1 study in patients surgically treated for aSAH and will investigate the effect of intracisternal
EG-1962 administration. The NEWTON (
Nimodipine microparticles to Enhance recovery While reducing TOxicity after
subarachNoid hemorrhage) trial is a phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation, safety, tolerability, and pharmacokinetic study comparing
EG-1962 and
nimodipine in patients with aneurysmal SAH.