Stroke, Acute Ischemic Clinical Trial
Official title:
The Efficacy and Safety of Y-3 Intracalvariosseous Injection Bypassing Blood-brain Barrier Versus Intravenous Injection in the Treatment of Acute Large Hemispheric Infarction（SOLUTION-2）
A pilot study confirmed the feasibility and safety of neuroprotectant Y-3 intracalvariosseous(ICO) injection in patients with malignant middle cerebral artery infarction (mMCAI), showing a trend in improving 90-day functional scores compared to conventional treatment. The aim of this trial is to further investigate the efficacy and safety of ICO injection of Y-3 compared to intravenous injection in patients with acute large hemispheric infarction(LHI) who has contraindications of reperfusion therapy or have got poor reperfusion therapy outcomes.
The mortality rate of large hemispheric infarction(LHI) is up to 40%-60%, while current available treatment is limited. Mainstream therapeutics include endovascular reperfusion therapy and decompressive craniectomy. But endovascular-reperfusion has limits such as short time window and hemorrhagic transformation risk, while decompressive craniectomy can reduce mortality but not infarct volume. Curative effect of intravenous injection of neuroprotective drugs is severely limited because of the blood-brain barrier. Microchannels connecting the skull bone marrow and dura may be effective drug delivery shortcuts bypassing the blood-brain barrier. Cytoprotective drug Y-3 affects dual aspects of ischemic cascade by disrupting both function of the synaptic folding post-synaptic density protein 95 (PSD-95), as well as α2-γ⁃Aminobutyric acid type A receptor (α2-GABAAR) agonist. Phase I and Phase II clinical trials have confirmed the safety and efficacy of intravenous infusion of Y-3 in treating cerebral infarction, with the optimal dosage being 40mg. Preclinical testing proved that ICO injection of Y-3 solution 24h post rat permanent middle cerebral artery infarction reduced rat infarction volume and improved neurological function. SOLUTION-2 is a multicentered, prospective, randomized, open-label, blinded end-point (PROBE) study The purpose of this study is to investigate the efficacy and safety of ICO injection of Y-3 compared to intravenous injection in acute LHI patients with contraindications of reperfusion therapy or poor outcomes. Patients will be randomly assigned to one of the following 2 groups at 1:1 ratio. ICO injection group: Y-3 ICO injection (dose was given as 32 ug/kg) once a day for 3 consecutive days, as well as standard treatment and management according to the related guidelines. intravenous injection group: Y-3 intravenous injection(dose was given as 40mg + 250ml normal saline), as well as standard treatment and management according to related guidelines. Face to face interviews will be made on baseline, 4±1 days after randomization, 8±1 days after randomization, 14±1 days after randomization or discharge day, and 90 days after randomization. The primary efficacy outcomes is the modified Rankin Scale（mRS） 0-3 points at 90±7 days. A Data and Safety Monitoring Board (DSMB) will regularly monitor safety during the study. The trial has been approved by Institutional Review Board (IRB) and Ethics Committee (EC) in Being Tiantan hospital, Capital Medical University. ;