Edaravone Dexborneol Sublingual Tablet for the PSCI in Acute Ischemic Stroke Patients

Official title

Efficacy and Safety of Edaravone Dexborneol Sublingual Tablet for Post-stroke Cognitive Impairment in Patients With Acute Ischemic Stroke: a Multicenter, Randomized, Double-blind, Placebo-controlled, Exploratory Phase II Clinical Trial.

Overview

This is a multicenter, randomized, double-blind, placebo-controlled, exploratory Phase II clinical trial. The goal of this clinical trial is to assess the safety and efficacy of edaravone dexborneol sublingual tablets for post-stroke cognitive impairment in patients with acute ischemic stroke. Participants will be required to receive 24 weeks treatment of edaravone dexborneol sublingual tablets or placebo during this study. The safety and efficacy endpoints will be compared in the patients with edaravone dexborneol sublingual tablets or placebo.

Interventions

• Drug Edaravone dexborneol sublingual tablet
  Patients will receive one edaravone dexborneol sublingual tablet twice daily for 24 weeks
• Drug Placebo
  Patients will receive one placebo twice daily for 24 weeks

Primary outcome measures

• Adverse Events [Time frame: Until follow up 26 weeks or early termination]
• Number of discontinuation/withdrawal patients [Time frame: Until follow up 26 weeks or early termination]
• The changes of the Vascular Dementia Assessment Scale-cognitive subscale (VaDAS-Cog) scores. [Time frame: Until follow up 24 weeks]

Secondary outcome measures (7)

• The incidence of Post Stroke Cognitive Impairment（PSCI ）in each group [Time frame: Week 12 and Week 24]
• The changes of Mini-Mental State Examination (MMSE) score [Time frame: Week 12 and Week 24]
• The changes of Montreal Cognitive Assessment (MoCA) scale [Time frame: Week 12 and Week 24]
• The changes of MoCA subscales [Time frame: Week 12 and Week 24]
• Modified Rankin Scale (mRS) scores [Time frame: Week 12 and Week 24]
• The changes of National Institutes of Health Stroke Scale [Time frame: Week 4 , Week 12 and Week 24]
• The changes of the Vascular Dementia Assessment Scale-cognitive subscale (VaDAS-Cog) scores. [Time frame: Week 12]

Eligibility criteria

Inclusion criteria

• Age ≥ 40 years and ≤ 80 years, male or female.
• Diagnosed as ischemic stroke, no significant pre-stroke functional disability (mRS score ≤ 1prior to stroke onset).
• The National Institutes of Stroke Scale score ≤ 20 points.
• Time from onset to obtained informed consent form is within 7 days (including 7 days).
• Presence of cognitive dysfunction at screening, i.e., MoCA scale score < 22.
• Patients with good cognitive function prior to stroke, without significant cognitive dysfunction and dementia.
• Education level: primary school or above, and can complete the cognitive function test required per investigator's judgement.
• female subjects of childbearing potential and male subjects whose female partners are of childbearing potential must be willing to and use contraception during the study treatment and within 30 days after the last dose of study drug and have no plans to donate sperm or eggs; female subjects of childbearing potential will have a negative pregnancy test;
• obtain voluntary signed informed consent from the patient or his/her legal representative approved by the Ethics Committee.

Exclusion criteria

• Presence of intracranial hemorrhagic disease confirmed by brain imaging.
• Severe disturbance of consciousness: NIHSS 1a level of consciousness item score > 1 point.
• Transient ischemic attack (TIA).
• Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 120 mmHg after blood pressure control.
• Poorly controlled diabetes (fasting blood glucose >10mmol/L and/or HbA1c>8%).
• Patients with contraindications to MRI imaging.
• For subjects who are scheduled to undergo EEG examination, Patients with contraindications for EEG examination.
• Presence of cognitive dysfunction prior to stroke assessed by informants, that is, the average score of Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE, 16-item version) during the screening period was ≥ 3.19 and the total score was ≥ 51.
• Patients who have been diagnosed with severe mental disorders prior to stroke.
• Severe limb hemiplegia and aphasia and significantly affect cognitive function assessment.
• Patients have received the cognitive enhancers and other anti-dementia drugs within 1 month before the screening period, including but not limited to cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists (memantine) and other drugs (such as mannitol sodium capsules, Ginkgo Biloba Extract Injection, Compound Ginkgo Biloba Tablets, oxiracetam, aniracetam, piracetam，nicergoline, Lecanemab, Donanemab, Aducanumab, etc. ).
• Have been diagnosed with severe active liver disease, such as acute hepatitis, chronic active hepatitis, cirrhosis, etc.; or ALT or AST > 2.0 × ULN.
• Has been diagnosed with severe active kidney disease, renal insufficiency; or serum creatinine > 1.5 × ULN.
• Thrombectomy or interventional therapy has been applied or planned after this episode.
• History of malignancy; except for subjects with non-melanoma skin cancer (NMSC) that has been successfully treated and limited cervical cancer in situ. Subjects with a diagnosis of malignancy after enrollment may continue to participate in the study or not at the discretion of the investigator and at the discretion of the subject;
• Suffering from a severe systemic disease with an expected survival period of <1 year;
• hypersensitivity to dextran camphene, natural ice chips or edaravone or excipients (mannitol, copovidone, microcrystalline cellulose, cross-linked povidone, silicon dioxide, magnesium stearate);
• pregnancy, lactation, and patients planning pregnancy;
• history of major surgery within 4 weeks prior to enrollment;
• participation in another clinical study within 30 days prior to randomization, or ongoing participation in another clinical study;
• in the opinion of the investigator, not suitable for participation in this clinical study.

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

Quadruple blind

Primary purpose

Treatment

Study locations

China · 21 centers

• Taihe County People's Hospital — Fuyang
• Hefei First People's Hospital — Hefei
• The First Affiliated Hospital of USTC Anhui Provincial Hospital — Hefei
• The Second People's Hospital of Hefei — Hefei
• Huangshan City People's Hospital — Huangshan City
• The Second Affiliated Hospital of Guangzhou Medical University — Guangzhou
• Wuzhou Red Cross Hospital — Wuzhou
• The Second Hospital of Hebei Medical University — Shijiazhuang
• … and 13 more centers

Identifiers

NCT: NCT06315231 · SIM0308-02-Y-2-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗