Isosorbide Mononitrate and Butylphthalide to Reduce the Risk of Disability in Patients With Acute Lacunar Stroke (IMPACT)

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 \<100 mmHg), bradycardia (heart rate \<60 bpm), sick sinus syndrome or severe cardiopulmonary disease.
• •8. History of congestive heart failure, acute myocardial infarction or other severe cardiac dysfunctions (NYHA Class III-IV).
• •9. Coagulation disorders, bleeding tendency or systemic bleeding, including but not limited to prothrombin time \>3×upper limit of normal (ULN), platelet count \<50×109/L, hemophilia, capillary fragility, gastrointestinal bleeding, urinary tract bleeding, hemoptysis, or vitreous hemorrhage, etc.
• •10. Severe hepatic or renal insufficiency (note: severe hepatic insufficiency is defined as ALT or AST \> 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.