Y-6 Sublingual Tablets for Patients With Acute Ischemic Stroke

Official title

Effects of Y-6 Sublingual Tablets for Patients With Acute Ischemic Stroke: a Randomised, Double-blind, Multicenter, Placebo-controlled Phase 3 Trial (FUTURE-2)

Overview

This study aims to evaluate the efficacy of Y-6 sublingual tablets in improving microcirculation dysfunction and reducing thrombo-inflammation in patients who had AIS caused by LVO and will receive EVT. Moreover, we expect to evaluate the safety of using Y-6 sublingual tablet in such study population. This study rationale is based on the following scheme: in patients with acute ischemic stroke caused by LVO, receiving reperfusion therapy may cause futile recanalization and thus lead to microcirculation dysfunction and thrombo-inflammation as consequences. Dexborneol has anti-inflammatory effects and Cilostazol has antiplatelet effects and BBB protection; therefore, the multi-component tablet may exert neuroprotective effects in terms of improving microcirculation dysfunction and reducing thrombo-inflammation in patients with AIS after reperfusion therapy. The primary purpose of this study is to investigate the proportion of modified-Rankin scale (mRS) score recovered to 0\~1 score at 90 days after randomization. The follow-up duration is 3 months, and the visit schedule is as follows: Subjects enrolled based on randomization procedures will receive visits at screening/baseline period, 1 day, 7 days, 28 days and 90 days after randomization, and in case of any events.

Interventions

• Drug Y-6
  each tablet of Y-6 contained 6 mg of dexborneol and 25 mg of cilostazol; Both groups took one tablet q12h for 28 days.
• Drug Y-6 placebo
  each tablet of Y-6 placebo contained 0.06 mg of dexborneol and 0 mg of cilostazol. Both groups took one tablet q12h for 28 days.

Primary outcome measures

• Proportion of subjects whose mRS recover to 0-1 at 90 days after randomization. [Time frame: 90 days]

Secondary outcome measures (4)

• •mRS at 90 days after randomization [Time frame: 90 days]
• • Changes in NIHSS from baseline to 1 day, 7 days and 28 days after randomization； [Time frame: from baseline to 1 day, 7 days and 28 days]
• • Proportion of patients with early neurological deterioration at 1 day after randomization; [Time frame: at 1 day]
• • Proportion of subjects with combined vascular events at 90 days after randomization. [Time frame: 90 days]

Eligibility criteria

Inclusion criteria

• 35 years old ≤ Age ≤ 80 years old;
• Patients with acute ischemic stroke diagnosed within 24 hours of onset (time from onset to start of endovascular treatment);
• Patients with first stroke or mRS score 0-1 prior to this onset ;
• Patients with acute intracranial large vessel occlusion (LVO) confirmed by imaging examination, including occlusion of intracranial segments of internal carotid arteries, T-shaped bifurcation, MCA M1 and/or M2 segments and ACA A1 and/or A2 segments;
• ASPECTS score ≥ 6 at screening;
• 6<NIHSS score ≤ 25 after this onset;
• Patients who had the indications for endovascular treatment and were scheduled for endovascular treatment;
• Patients or his/her legal representatives were able to understand and sign the informed consent.

Exclusion criteria

• Patients who are allergic to the active ingredients or excipients of investigational products；
• Severe disorder of consciousness at screening: NIHSS 1a consciousness level ≥2 points;
• Patients with previously diagnosed intracranial haemorrhage at screening, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/external hematoma, etc.;
• Patients with previously diagnosed intracranial tumor, arteriovenous malformation, or aneurysm at screening;
• Patients with previously diagnosed congestive heart failure at screening;
• Patients with bilateral LVO at anterior circulation or LVO at posterior circulation or LVO of unknown aetiology at screening;
• Patients who have received treatment with warfarin, novel oral anticoagulants, argatroban, snake venom, defibrase, lumbrokinase and batroxobin after onset;
• Patients with severe hematologic abnormality or severe hepatic insufficiency or renal insufficiency and received dialysis for various reasons at screening (hematologic abnormality was defined as platelet count <100×109/L; severe hepatic insufficiency was defined as ALT > 3 × ULN or AST >3 × ULN; severe renal insufficiency was defined as serum creatinine >3.0 mg/dl (265.2 μmol/L) or creatinine clearance < 30 ml/min);
• Patients with previously diagnosed hemorrhagic tendency (including but not limited to): hemorrhagic retinopathy or hereditary hemorrhagic disorders, such as hemophilia, at screening;
• Patients with refractory hypertension that is difficult to be controlled by medication (systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg);
• Patients with history of major head trauma or stroke within 1 month prior to randomization;
• Patients who have received intracranial or spinal surgery within 3 months prior to randomization;
• Patients with history of major surgery or serious physical trauma within 1 month prior to randomization;
• Male subjects (or their mates) or female subjects who had planned to have a child during the whole study period and within 3 months after the end of the study period or were unwilling to use one or more non-drug contraceptive methods (e.g., complete abstinence, condoms, ligation, etc.) during the study period;
• Patients with contraindications to known contrast agents or other contrast agents;
• Patients who plan to receive other surgical or intervention therapy within 3 months, which might require discontinuation of the study drugs;
• Patients with life expectancy of less than 3 months;
• Patients who have received treatment of investigational drugs or devices within previous 3 months;
• Other investigator-evaluated conditions which may influence the compliance of patients or where it is not suitable for patients to participate in this trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07040085 · YW2025-020-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗