Cerebral small vascular disease
Conditions
Interventions
Isosorbide mononitrate plus butylphthalide group:Days 1–7: Isosorbide mononitrate injection, 20 mg once daily by intravenous infusion
butylphthalide injection, 25 mg twice daily by intravenous infusion.
Days 8–6 months: Isosorbide mononitrate sustained-release tablets, 40 mg once daily orally (dose reduced to 20 mg once daily during
butylphthalide soft capsules, 200 mg three times daily orally.
Isosorbide mononitrate plus butylphthalide placebo group:Days 1–7: Isosorbide mononitrate injection, 20 mg once daily by intravenous infusion
butylphthalide injection placebo, twice daily by intravenous infusion.
Days 8–6 months: Isosorbide mononitrate sustained-release tablets, 40 mg once daily orally (dose reduced to 20 mg once daily duri
butylphthalide soft capsule placebo, 2 capsules three times daily orally.
Isosorbide mononitrate placebo plus butylphthalide group:Days 1–7: Isosorbide mononitrate injection placebo, once daily by intravenous infusion
butylphthalide injection, 25 mg twice daily by intravenous infusion.
Days 8–6 months: Isosorbide mononitrate sustained-release tablet placebo, once daily orally (dose reduced to half a tablet once dai
Isosorbide mononitrate placebo plus butylphthalide placebo group:Days 1–7: Isosorbide mononitrate injection placebo, once daily by intravenous infusion
butylphthalide injection placebo, twice daily by intravenous infusion.
Days 8–6 months: Isosorbide mononitrate sustained-release tablet placebo, once daily orally (dose reduced to half a tablet once d
Sponsors
Beijing Tiantan Hospital, Capital Medical University; Shenzhen Second People's Hospital
Eligibility
Sex/Gender
All
Age
30 Years to No maximum
Inclusion criteria
Inclusion criteria: 1) Age >= 30 years; 2) Clinical lacunar syndrome within 7 days; 3) Brain CT/MRI after symptom onset: a. a relevant (in time and location) acute lacunar infarct; b. if no relevant lesion, symptom duration >24 hours, with no other suspected stroke etiologies (such as cerebral hemorrhage, cortical infarction, seizures, etc.) 4) MoCA score meeting the following criteria: a. MoCA >= 13 if educated = 15 if 7 = 18 if educated >= 13 years; 5) mRS <= 1 prior to this episode; 6) Patient or a legally authorized representative signed informed consent.
Exclusion criteria
Exclusion criteria: 1) Ischemic stroke of large artery atherosclerosis, cardioembolism, or other etiologies (TOAST classification); 2) Diagnosed or suspected hereditary CSVD; 3) Intracerebral hemorrhage within the past 3 months including parenchymal, intraventricular, subarachnoid hemorrhage, subdural/epidural hematoma; 4)Neurodegenerative diseases or systemic diseases that may lead to cognitive impairment, such as Alzheimer's disease, mixed dementia, Parkinson's disease, systemic autoimmune diseases, hepatic encephalopathy, or uremic encephalopathy; 5)Previously diagnosed psychiatric disorders (DSM-5 criteria); 6)Other active neurological disorders (e.g., recurrent seizures, brain tumors, vascular malformations, untreated aneurysms >3 mm); 7)Hypotension (seated systolic blood pressure 3×upper limit of normal (ULN), platelet count 3×ULN or acute hepatitis, chronic active hepatitis, cirrhosis; severe renal insufficiency is defined as eGFR < 45 ml/min/1.73m², creatinine clearance < 40 ml/min, or known chronic kidney disease of stage 3 or higher); 11)Head trauma, intracranial or spinal surgery, major surgical procedures or severe trauma within the past 4 weeks; 12)ISMN or NBP use within the past 3 days; 13)Have contraindications to ISMN or NBP, or allergy to their components; 14)Have to use the contraindicated drugs of this trial for a long time; 15)Pregnant, breastfeeding or planning to pregnant during this study; 16)Unable to tolerate MRI or with MRI contraindications; 17)Have severe diseases or expected survival <12 months; 18)Participate in other clinical trials within 30 days before this trial; 19)Unlikely to comply with study procedures and follow-up procedures for whatever reason in the opinion of the research physician.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Post-stroke disability at 6 months (modified Rankin Scale [mRS] score = 3, major adverse cardiovascular events [MACE], cognitive impairment, and all-cause mortality);Moderate or more severe headache within 6 months; | — |
Secondary
| Measure | Time frame |
|---|---|
| Post-stroke disability at 1 year (modified Rankin Scale [mRS] score = 3, major adverse cardiovascular events [MACE], cognitive impairment, and all-cause mortality);mRS score = 3 at 6 months and 1 year;Recurrent stroke at 6 months and 1 year;Dementia at 6 months and 1 year;National Institutes of Health Stroke Scale (NIHSS) scores at 7 days, 6 months, and 1 year (including changes from baseline);= 80% of patients taking = 50% of the trial dose up to 6 months;Imaging and blood biomarkers predictive of drug efficacy at 6 months and 1 year;Changes in cerebral hemodynamics at 6 months and 1 year;Changes in each cognitive domain at 6 months and 1 year;Hypotension within 6 months;Syncope within 6 months;Liver function impairment within 6 months;Any bleeding within 6 months;Symptomatic intracranial hemorrhage within 6 months; | — |
Countries
China
Contacts
Public ContactWang Yilong
Beijing Tiantan Hospital, Capital Medical University
Outcome results
None listed