STRIVE-ON: Safety and ToleRability of GTX-104 (Nimodipine Injection for IV Infusion) ComparEd with Oral Nimodipine in Patients Hospitalized for Aneurysmal Subarachnoid Hemorrhage (aSAH): a Prospective, Randomized Trial (STRIVE-ON)

Oral nimodipine is the only drug approved in North America for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). However, bioavailability is variable and frequently poor, leading to fluctuations in peak plasma concentrations that cause dose-limiting hypotension. Furthermore, administration is problematic in patients who cannot swallow capsules. An oral liquid formulation exists but causes gastrointestinal complications. An intravenous nimodipine formulation (GTX-104) has been developed that has bioavailability approaching 100% and is not affected by feeding or gastointestinal absorption. GTX-104 causes less hypotension and has more consistent peak plasma concentrations than oral nimodipine in healthy human volunteers. Herein we describe the protocol of a prospective, randomized, open-label safety and tolerability study of GTX-104 compared to oral nimodipine in patients with aSAH (STRIVE-ON, NCT05995405). Inclusion and exclusion criteria match the prescribing information for oral nimodipine and include adult patients with aSAH of all Hunt and Hess grades who can receive investigational product within 96 hours of aSAH. Subjects at imminent risk of death are excluded. Subjects are randomized 1:1 to GTX-104 or oral nimodipine for up to 21 days. The primary endpoint is the proportion of subjects in each group with clinically significant hypotension, defined as hypotension requiring any medical treatment, with a reasonable likelihood of being due to investigational product as determined by an independent, blinded endpoint adjudication committee. No statistical analysis of the endpoint is planned. Secondary endpoints include all episodes of hypotension, all adverse events, delayed cerebral ischemia, rescue therapy and suicidal ideation. Clinical and health economic outcomes include quality of life using the EQ-5D-3L, modified Rankin scale at 30 and 90 days after aSAH and hospital resource use. The planned sample size is 100 subjects across 25 sites in the United States and Canada. DETAILS PAGEO_LIWe confirm that manuscript complies with all instructions to authors. C_LIO_LIWe confirm that authorship requirements have been met and the final manuscript is approved by all authors. C_LIO_LIWe confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. It is planned to post it on C_LIO_LIWe confirm adherence to ethical guidelines and indicate ethical approvals and use of informed consent. C_LIO_LIAll conflicts of Interest for all authors are disclosed. C_LIO_LIWe confirm the use of the Standard Protocol Items: Recommended for Interventional Trials (SPIRIT) checklist. C_LIO_LIThe source of funding for the study is disclosed. It is Acasti Pharma. C_LI