EFfects of Y-6 SUblingual Tablets foR PaTients With AcUte Ischemic StRokE (FUTURE)

Phase 2

Not yet recruiting

• Conditions: Reperfusion; Large Vessel Occlusion; Acute Ischemic Stroke
• Interventions: Drug: High-dose Y-6 sublingual tablets; Drug: Low-dose Y-6 sublingual tablets; Drug: Placebo; Drug: Low-dose Cilostazol; Drug: High-dose Cilostazol

• Registration Number: NCT06138834
• Lead Sponsor: Beijing Tiantan Hospital

Brief Summary

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 received reperfusion therapy. Moreover, we expect to evaluate the safety of using Y-6 sublingual tablet in such study population.

Detailed Description

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. Cilostazol has antiplatelet effects and BBB protection and Dexborneol has anti-inflammatory effects; 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±7 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, 24 ± 2 hours, 7 ± 2 days, 28 + 3 days and 90 ± 7 days after randomization, and in case of any events.

Study Timeline

• Status Verified: 2023-11
• Study Start: 2023-11
• Study First Submitted: 2023-11-14
• Study First Submitted QC: 2023-11-14
• Last Update Submitted: 2023-11-14
• Study First Posted: 2023-11-18
• Last Update Posted: 2023-11-18
• Primary Completion: 2024-11
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

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 when screening;
• 6<NIHSS score ≤ 25 after this onset;
• Patients who had the indications for mechanical thrombectomy and were scheduled for endovascular treatment;
• Patients or his/her legal representatives were able to understand and sign the informed consent.

Exclusion Criteria

• Severe disorder of consciousness: NIHSS 1a consciousness level ≥2 points;
• Patients with definite history of intracranial hemorrhage, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/external hematoma, etc. when screening;
• Patients with previously diagnosed intracranial tumor, arteriovenous malformation, or aneurysm when screening;
• Patients with bilateral LVO at anterior circulation or LVO at posterior circulation when screening;
• Patients with LVO of unknown or rare etiology, e.g., due to dissection, vasculitis, etc. when screening;
• Patients who have received treatment with tirofiban, warfarin, novel oral anticoagulants, argatroban, snake venom, defibrase, lumbrokinase or other defibrase therapy after onset, or platelet count <100×10^9/L;
• Patients with severe hepatic insufficiency or renal insufficiency and received dialysis for various reasons when screening (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): with hereditary hemorrhagic disorders, such as hemophilia, when 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;
• Patients with previously diagnosed hemorrhagic retinopathy;
• 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 are allergic to Cilostazol or Dexborneol;
• 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 due to advanced stage of comorbidity;
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High-dose Y-6 sublingual tablet group	High-dose Y-6 sublingual tablets	Two Y-6 sublingual tablets (each tablet contains 25 mg Cilostazol and 6 mg Dexborneol), and two halves Cilostazol mimicry tablets (each tablet contains 0 mg Cilostazol).
Low-dose Y-6 sublingual tablet group	Low-dose Y-6 sublingual tablets	One Y-6 sublingual tablet (each tablet contains 25 mg Cilostazol and 6 mg Dexborneol), one placebo of Y-6 sublingual tablet (each tablet contains 0 mg Cilostazol and 0.06 mg Dexborneol to simulate the cool taste of Y-6 sublingual tablets when taken), and two halves Cilostazol mimicry tablets (each tablet contains 0 mg Cilostazol).
Placebo group	Placebo	Two tablets of placebo of Y-6 sublingual tablets (each tablet contains 0 mg Cilostazol and 0.06 mg Dexborneol to simulate the cool taste of Y-6 sublingual tablets when taken), and two halves Cilostazol mimicry tablets (each tablet contains 0 mg Cilostazol).
Low-dose Cilostazol group	Low-dose Cilostazol	Two tablets of placebo of Y-6 sublingual tablets (each tablet contains 0 mg Cilostazol and 0.06 mg Dexborneol to simulate the cool taste of Y-6 sublingual tablets when taken), one half Cilostazol tablet (each tablet contains 50 mg Cilostazol), and one half Cilostazol mimicry tablet(each tablet contains 0 mg Cilostazol).
High-dose Cilostazol group	High-dose Cilostazol	Two tablets of placebo of Y-6 sublingual tablets (each tablet contains 0 mg Cilostazol and 0.06 mg Dexborneol to simulate the cool taste of Y-6 sublingual tablets when taken), and two halves Cilostazol tablet (each tablet contains 50 mg Cilostazol).

Primary Outcome Measures

Name	Time	Method
Proportion of mRS score recovered to 0~1 score	At 90±7 days after randomization	The modified Rankin Scale (mRS) decreasing to 0\~1 score. mRS Mainly measures patients' independent living ability, including physical function, activity ability and participation in daily life. A score of 0 on the mRS Scale indicates no symptoms and a score of 5 indicates severe disability.

Secondary Outcome Measures

Name	Time	Method
Changes of NIHSS score between baseline and at 24 ± 2 hours, 7 ± 2 days and 28 + 3 days after randomization	At 24 ± 2 hours, 7 ± 2 days and 28 + 3 days after randomization	NIHSS score after reperfusion therapy within 2 hours changing compared with baseline NIHSS. The NIHSS score ranges from 0 to 42. The higher the score, the more severe the nerve damage.
The mRS score at 90±7 days after randomization	At 90±7 days after randomization	The modified Rankin Scale (mRS) decreasing to 0\~1 score. mRS Mainly measures patients' independent living ability, including physical function, activity ability and participation in daily life. A score of 0 on the mRS Scale indicates no symptoms and a score of 5 indicates severe disability.
Proportion of patients with combined vascular events at 90 ± 7 days after randomization	At 90 ± 7 days after randomization	Combined vascular events were defined as: symptomatic stroke, myocardial infarction and vascular death.
Proportion of patients with early progression of stroke at 24 ± 2 hours after randomization	At 24 ± 2 hours after randomization	Early progression of stroke was defined as: within 7 days after onset, compared to baseline, an increase of ≥ 2 points in NIHSS; or an increase of ≥ 1 point in limb hemiplegia; or an increase of ≥ 1 point in consciousness disorder, excluding those caused by intracranial hemorrhage and other non-stroke causes such as cardiac insufficiency, liver insufficiency, renal insufficiency, etc.