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

Acute Ischemic Stroke Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06138834
• Other study ID #: YW2023-038-02
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 2023
• Est. completion date: January 2025

Study information

• Verified date: November 2023
• Source: Beijing Tiantan Hospital
• Contact: Yilong Wang, PhD+MD
• Phone: 0086-010-67092222
• Email: yilong528[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: January 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Large Vessel Occlusion
• Reperfusion
• Stroke

Intervention

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.
• 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.
• 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.
• 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
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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital	NeuroDawn Pharmaceutical Co., Ltd.

References & Publications (14)

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Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18. — View Citation

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* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of mRS score recovered to 0~1 score	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.	At 90±7 days after randomization
Secondary	The mRS 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.	At 90±7 days after randomization
Secondary	Changes of NIHSS score between baseline and 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.	At 24 ± 2 hours, 7 ± 2 days and 28 + 3 days after randomization
Secondary	Proportion of patients with early progression of stroke 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.	At 24 ± 2 hours after randomization
Secondary	Proportion of patients with combined vascular events at 90 ± 7 days after randomization	Combined vascular events were defined as: symptomatic stroke, myocardial infarction and vascular death.	At 90 ± 7 days after randomization