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

Prior treatment

• Previously diagnosed psychiatric disorders (DSM-5 criteria).
• Head trauma, intracranial or spinal surgery, major surgical procedures or severe trauma within the past 4 weeks.
• Have to use the contraindicated drugs of this trial for a long time.
• Participate in other clinical trials within 30 days before this trial.

Other illness

• Ischemic stroke of large artery atherosclerosis, cardioembolism, or other etiologies (TOAST classification);
• Intracerebral hemorrhage within the past 3 months including parenchymal, intraventricular, subarachnoid hemorrhage, subdural/epidural hematoma;
• 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.
• Other active neurological disorders (e.g., recurrent seizures, brain tumors, vascular malformations, untreated aneurysms \>3 mm).
• Hypotension (seated systolic blood pressure \<100 mmHg), bradycardia (heart rate \<60 bpm), sick sinus syndrome or severe cardiopulmonary disease.
• History of congestive heart failure, acute myocardial infarction or other severe cardiac dysfunctions (NYHA Class III-IV).
• Have contraindications to ISMN or NBP, or allergy to their components.
• Have severe diseases or expected survival \<12 months.

Lab values

• 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.
• 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).

Other

• Diagnosed or suspected hereditary CSVD;
• ISMN or NBP use within the past 3 days.
• Pregnant, breastfeeding or planning to pregnant during this study.
• Unable to tolerate MRI or with MRI contraindications.
• Unlikely to comply with study procedures and follow-up procedures for whatever reason in the opinion of the research physician.

• Age ≥ 30 years;
• Clinical lacunar syndrome within 7 days;
• Brain CT/MRI after symptom onset:
  • a relevant (in time and location) acute lacunar infarct;
  • if no relevant lesion, symptom duration \>24 hours, with no other suspected stroke etiologies (such as cerebral hemorrhage, cortical infarction, seizures, etc.)
• MoCA score meeting the following criteria:
  • MoCA ≥ 13 if educated ≤ 6 years;
  • MoCA ≥ 15 if 7 ≤ educated ≤ 12 years;
  • MoCA ≥ 18 if educated ≥ 13 years；
• mRS ≤ 1 prior to this episode;
• Patient or a legally authorized representative signed informed consent.