Effect of Butyphthalide on Cognitive Level Change After Cerebral Vascular Event-a Randomized Control Trial (Be-CLEVER)
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age60+
SponsorFudan University
About this trial
Post-stroke cognitive impairment (PSCI) refers to a clinical syndrome characterized by cognitive impairment that occurs after a stroke event and persists for at least 24 weeks. Due to the early recovery of conditions such as delirium and transient cognitive impairment after stroke, the diagnosis of PSCI often requires cognitive assessment at 12 to 24 weeks post-stroke to determine the severity of cognitive impairment. It can be classified according to the severity of cognitive impairment as post-stroke cognitive impairment no dementia (PSCIND) and post-stroke dementia (PSD). Recent large international cohort studies have reported an incidence rate of PSCI ranging from 24% to 53.4%, and patients with PSCI have a significantly higher mortality rate compared to those without cognitive impairment. Guidelines such as American Heart Association/American Society of Anesthesiologists (AHA/ASA) and the Chinese "Expert Consensus on the Management of Post-Stroke Cognitive Impairment" propose integrating cognitive impairment and stroke intervention strategies. Early comprehensive intervention and treatment for high-risk individuals after stroke, aiming to delay or prevent the progression from PSCIND to PSD, are the primary goals in the current treatment of PSCI. However, there is currently a lack of large randomized controlled trials (RCTs) for PSCI, and research is still needed to determine whether cognitive-enhancing drugs can reduce the risk of PSCI occurrence and improve outcomes and prognosis for PSCI patients. A randomized, double-blind, multicenter clinical study involving 281 non-dementia vascular cognitive impairment (VCI) patients showed that the overall cognitive scores of patients treated with donepezil for 24 weeks significantly improved compared to the placebo group.
The aim of this study is to evaluate the effectiveness of donepezil in the treatment of post-stroke cognitive impairment. It will be a multicenter, randomized, double-blind, placebo-controlled trial with a 48-week treatment duration. The study will observe the difference in PSCI incidence rate between the donepezil treatment group and the conventional stroke treatment group at 24 weeks and evaluate the improvement in post-stroke cognitive impairment after 6 months of donepezil treatment compared to conventional treatment.
This study will be conducted in two stages: the first stage (0-24 weeks) aims to assess whether donepezil can reduce the risk of PSCI occurrence and will be a multicenter, randomized, double-blind, placebo-controlled study. The second stage (24-48 weeks) aims to evaluate whether donepezil can improve the prognosis of PSCI patients and will also be a multicenter, randomized, double-blind, placebo-controlled study.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Acute ischemic stroke (AIS) symptom onset within 14 days Signs and symptoms consistent with the diagnosis of an acute ischemic stroke by CT/MRI.
Age >= 60 years，
Baseline NIHSS 3-18.
Patient can complete questionnaire survey, physical examination, cranial MRI and other medical examinations
Disqualifiers
Patients who had been diagnosed with dementia prior to stroke
Other related factors affecting cognitive function: central nervous system infection, neurodegenerative diseases, trauma, poisoning, intracranial space occupying lesions, metabolic diseases, etc.
Other serious central nervous system diseases: Parkinson's disease, epilepsy, multiple sclerosis, motor neurone disease, immune-related encephalomyelopathy, etc.
Serious mental illness: anxiety disorder, depression, delirium, schizophrenia, bipolar disorder, mental retardation, which is diagnosed or controlled by medication.
Trial design
Design model
Parallel
Treatments tested in this trial
dl-3-butylphthalide
DrugFirst stage： Routine stroke treatment: hypoglycemic, antihypertensive, antiplatelet, anticoagulant and other conventional cerebrovascular disease treatment drugs. Placebo group: routine stroke treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 24 weeks. Butylphthalide group: routine stroke treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 24 weeks. Second stage： 14d washout period after first stage. Routine PSCI treatment: 5-10 mg Donepezil, qd. Placebo group: Routine PSCI treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 24 weeks. Butylphthalide group: Routine PSCI treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 24 weeks.
dl-3-butylphthalide placebo
DrugFirst stage： Routine stroke treatment: hypoglycemic, antihypertensive, antiplatelet, anticoagulant and other conventional cerebrovascular disease treatment drugs. Placebo group: routine stroke treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 24 weeks. Butylphthalide group: routine stroke treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 24 weeks. Second stage： 14d washout period after first stage. Routine PSCI treatment: 5-10 mg Donepezil, qd. Placebo group: Routine PSCI treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 24 weeks. Butylphthalide group: Routine PSCI treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 24 weeks.
Treatment groups
3,200 Participants
are divided into 2 treatment groupsGroup A: dl-3-butylphthalideExperimental treatment 2 interventions
Group B: dl-3-butylphthalide PlaceboPlacebo comparator 2 interventions
Trial outcomes
Primary outcomes
1
PSCI incidence
Compared with routine stroke treatment, the difference of the PSCI incidence at 24 weeks with butylphthalide treatment.
Time frame
24 weeks (first stage)2
vadas-cog score
Compared with routine treatment, improvement of vadas-cog scores at 24 weeks with butylphthalide treatment
Time frame
6 months (Second stage)Secondary outcomes
1
Changes of Montreal Cognitive Assessment (MoCA) at 24 weeks compared with baseline
Changes of Montreal Cognitive Assessment (MoCA) at 24 weeks compared with baseline
Time frame
24 weeks (first stage)2
Changes of Mini-Mental State Examination (MMSE) at 24 weeks compared with baseline
Changes of Mini-Mental State Examination (MMSE) at 24 weeks compared with baseline
Time frame
24 weeks (first stage)3
Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 24 weeks compared with baseline
Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 24 weeks compared with baseline
Time frame
24 weeks (first stage)4
Changes of Hamilton Anxiety Scale (HAMA) at 24 weeks compared with baseline
Changes of Hamilton Anxiety Scale (HAMA) at 24 weeks compared with baseline
Time frame
24 weeks (first stage)Other outcomes
1
Incidence of Treatment-Emergent Adverse Events [Safety]
Incidence of Treatment-Emergent Adverse Events \[Safety\]
Time frame
12 weeks, 24 weeks, 36 weeks and 48 weeks2
Dropout rates and reasons [Safety]
Dropout rates and reasons \[Safety\]
Time frame
12 weeks, 24 weeks, 36 weeks and 48 weekssSponsors and contacts
Click on the lead sponsor to view all of their trials.
Fudan University
Lead sponsor
Huashan Hospital
Sponsor institution
Source ClinicalTrials.gov