Clinical trial NCT06138834: EFfects of Y-6 SUblingual Tablets foR PaTients With AcUte Ischemic StRokE (FUTURE)
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Large Vessel Occlusion
Reperfusion
Keywords: Y-6
cilostazol
dexborneol
acute ischemic stroke
large vessel occlusion
reperfusion therapy
FUTURE
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Neurodawn Pharmaceutical Co., Ltd.
First posted: 2023-11-18
Enrollment: 300
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Proportion of mRS score recovered to 0~1 score
timeFrame: At 90±7 days after randomization
Secondary outcomes:
measure: The mRS score at 90±7 days after randomization
timeFrame: At 90±7 days after randomization
measure: Changes of NIHSS score between baseline and at 24 ± 2 hours, 7 ± 2 days and 28 + 3 days after randomization
timeFrame: At 24 ± 2 hours, 7 ± 2 days and 28 + 3 days after randomization
measure: Proportion of patients with early progression of stroke at 24 ± 2 hours after randomization
timeFrame: At 24 ± 2 hours after randomization
measure: Proportion of patients with combined vascular events at 90 ± 7 days after randomization
timeFrame: At 90 ± 7 days after randomization
Other outcomes:
Locations:
Study officials:
affiliation: Beijing Tiantan Hospital, Capital Medical University, Beijing, China
name: Yilong Wang, PhD+MD
role: PRINCIPAL_INVESTIGATOR
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