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

Sponsor

Beijing Tiantan Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06138834

Collaborator

NeuroDawn Pharmaceutical Co., Ltd. (Other)

300

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Ischemic Stroke Large Vessel Occlusion Reperfusion	Drug: Low-dose Y-6 sublingual tablets Drug: High-dose Y-6 sublingual tablets Drug: Low-dose Cilostazol Drug: High-dose Cilostazol Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effects of Y-6 Sublingual Tablets for Patients With Acute Ischemic Stroke: A Phase Ⅱ, Randomized, Double-blind, Double-dummy, Placebo-controlled Parallel Trial

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low-dose Y-6 sublingual tablet group 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).	Drug: Low-dose Y-6 sublingual tablets Take 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) for 28 days continuously.
Experimental: High-dose Y-6 sublingual tablet group 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).	Drug: High-dose Y-6 sublingual tablets Take 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) for 28 days continuously.
Experimental: Low-dose Cilostazol group 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).	Drug: Low-dose Cilostazol Take 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) for 28 days continuously.
Experimental: High-dose Cilostazol group 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).	Drug: High-dose Cilostazol Take 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) for 28 days continuously.
Placebo Comparator: Placebo group 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).	Drug: Placebo Take 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) for 28 days continuously.

Outcome Measures

Primary Outcome Measures

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

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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.