Clinical trial NCT06315231: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Post-stroke Cognitive Impairment
Lead sponsor: Simcere Pharmaceutical Co., Ltd
Sponsor class: OTHER
First posted: 2024-03-18
Enrollment: 200
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 40 years and ≤ 80 years, male or female.
2. Diagnosed as ischemic stroke, no significant pre-stroke functional disability (mRS score ≤ 1prior to stroke onset).
3. The National Institutes of Stroke Scale score ≤ 20 points.
4. Time from onset to obtained informed consent form is within 7 days (including 7 days).
5. A baseline MMSE score of mild dementia severity was required: ≤20 points for subjects with elementary school education and ≤24 points for subjects with secondary school education and above for mild dementia severity;
6. Presence of cognitive dysfunction at screening, i.e., MoCA scale score \< 22.
7. Patients with good cognitive function prior to stroke, without significant cognitive dysfunction and dementia.
8. Education level: primary school or above, and can complete the cognitive function test required per investigator's judgement.
9. 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;
10. obtain voluntary signed informed consent from the patient or his/her legal representative approved by the Ethics Committee.

Exclusion Criteria:

1. Presence of intracranial hemorrhagic disease confirmed by brain imaging.
2. Severe disturbance of consciousness: NIHSS 1a level of consciousness item score \> 1 point.
3. Transient ischemic attack (TIA).
4. Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 120 mmHg after blood pressure control.
5. Poorly controlled diabetes (fasting blood glucose \>10mmol/L and/or HbA1c\>8%).
6. Patients with contraindications to MRI imaging.
7. Patients with contraindications for EEG examination.
8. 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.
9. Patients who have been diagnosed with severe mental disorders prior to stroke.
10. Severe limb hemiplegia and aphasia and significantly affect cognitive function assessment.
11. 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. ).
12. Have been diagnosed with severe active liver disease, such as acute hepatitis, chronic active hepatitis, cirrhosis, etc.; or ALT or AST \> 2.0 × ULN.
13. Has been diagnosed with severe active kidney disease, renal insufficiency; or serum creatinine \> 1.5 × ULN.
14. Thrombectomy or interventional therapy has been applied or planned after this episode.
15. 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;
16. Suffering from a severe systemic disease with an expected survival period of \<1 year;
17. hypersensitivity to dextran camphene, natural ice chips or edaravone or excipients (mannitol, copovidone, microcrystalline cellulose, cross-linked povidone, silicon dioxide, magnesium stearate);
18. pregnancy, lactation, and patients planning pregnancy;
19. history of major surgery within 4 weeks prior to enrollment;
20. participation in another clinical study within 30 days prior to randomization, or ongoing participation in another clinical study;
21. in the opinion of the investigator, not suitable for participation in this clinical study.

Primary outcomes:
measure: Adverse Events
timeFrame: Until follow up 26 weeks or early termination
measure: Number of discontinuation/withdrawal patients
timeFrame: Until follow up 26 weeks or early termination
measure: The changes of the Vascular Dementia Assessment Scale-cognitive subscale (VaDAS-Cog) scores.
timeFrame: Until follow up 24 weeks
Secondary outcomes:
measure: The incidence of Post Stroke Cognitive Impairment（PSCI ）in each group
timeFrame: Week 12 and Week 24
measure: The changes of Mini-Mental State Examination (MMSE) score
timeFrame: Week 12 and Week 24
measure: The changes of Montreal Cognitive Assessment (MoCA) scale
timeFrame: Week 12 and Week 24
measure: The changes of MoCA subscales
timeFrame: Week 12 and Week 24
measure: Modified Rankin Scale (mRS) scores
timeFrame: Week 12 and Week 24
measure: The changes of National Institutes of Health Stroke Scale
timeFrame: Week 4 , Week 12 and Week 24
measure: The changes of the Vascular Dementia Assessment Scale-cognitive subscale (VaDAS-Cog) scores.
timeFrame: Week 12
Other outcomes:
Locations:
city: Fuyang
country: China
facility: Taihe County People's Hospital
state: Anhui
city: Hefei
country: China
facility: Hefei First People's Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The Second People's Hospital of Hefei
state: Anhui
city: Huangshan
country: China
facility: Huangshan City People's Hospital
state: Anhui
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Wuzhou
country: China
facility: Wuzhou Red Cross Hospital
state: Guangxi
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Zhumadian
country: China
facility: Zhumadian Central Hospital
state: Henan
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Benxi
country: China
facility: Liaoning Health Industry Group Bensteel General Hospital
state: Liaoning
city: Dalian
country: China
facility: The First Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First People's Hospital of Shenyang
state: Liaoning
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical College
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Taian
country: China
facility: Tai'an Central Hospital
state: Shandong
city: Suining
country: China
facility: Suining Central Hospital
state: Sichuan
city: Zhuji
country: China
facility: Zhuji People's Hospital of Zhejiang Province
state: Zhe Jiang
city: Dongyang
country: China
facility: Dongyang People's Hospital
state: Zhejiang
city: Huzhou
country: China
facility: The First People's Hospital of Huzhou
state: Zhejiang
Study officials:
References: