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

NCT07252544 | Not Yet Recruiting Phase 3

• 1 other identifier: 2023ZD0504802
• Study Type: interventional
• Target: 3,156
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this multicenter, double-blind, 2×2 factorial randomized controlled trial is to evaluate the efficacy and safety of isosorbide mononitrate, butylphthalide, and their combination in reducing disability in patients with acute lacunar stroke.

Conditions

Stroke, Lacunar; Stroke, Acute Ischemic; Cerebral Small Vessel Diseases

Outcome Measures

Primary Outcomes (2)

• Proportion of participants with post-stroke disability at 6 months

  A composite endpoint defined as the occurrence of any of the following: modified Rankin Scale (mRS) score ≥ 3, major adverse cardiovascular events (MACE), cognitive impairment, or all-cause mortality. The mRS measures post-stroke functional outcome on a scale from 0 (no symptoms) to 6 (death). MACE includes non-fatal stroke, non-fatal myocardial infarction (MI), and vascular death.The assessment of cognitive function involves three stages: a cognitive screening test, supplementary cognitive testing, and adjudication by an expert panel. The Beijing version of the Montreal Cognitive Assessment (MoCA) is used as the cognitive screening scale. Scores on the MoCA range from 0 to 30, with lower scores indicating greater cognitive impairment.The supplementary cognitive assessment includes the evaluation of several domains: executive function, attention and processing speed, language, and memory, as well as activities of daily living.

  6 months

• Incidence of moderate or more severe headache within 6 months

  Headache severity is assessed using the Numerical Rating Scale (NRS), where: 0 indicates no pain; 1 represents a mild headache (including feelings of head pressure or throbbing that are not considered painful); a score of 4 or higher (≥4) represents a headache of at least moderate intensity; and 10 represents the worst headache imaginable to the subject.

  6 months

Secondary Outcomes (10)

• Proportion of participants with post-stroke disability at 1 year

  1 year

• Proportion of participants with the modified Rankin Scale (mRS) score ≥ 3 at 6 months and 1 year

  6 months and 1 year

• Incidence of recurrent stroke within 6 months and 1 year

  6 months and 1 year

• Proportion of participants with dementia at 6 months and 1 year

  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)

  baseline, 7 days, 6 months, and 1 year

Other Outcomes (17)

• ≥ 80% of patients taking ≥ 50% of the trial dose up to 6 months

  6 months

• Concentration of blood biomarkers predictive of drug efficacy at 6 months and 1 year

  baseline, 6 months and 1 year

• Changes in white matter integrity at 6 months and 1 year

  baseline, 6 months and 1 year

Study Arms (4)

isosorbide mononitrate plus butylphthalide

EXPERIMENTAL

Drug: Isosorbide Mononitrate; Drug: Butylphthalide

isosorbide mononitrate plus butylphthalide placebo

EXPERIMENTAL

Drug: Isosorbide Mononitrate; Drug: Butylphthalide Placebo

isosorbide mononitrate placebo plus butylphthalide

EXPERIMENTAL

Drug: Butylphthalide; Drug: Isosorbide Mononitrate Placebo

isosorbide mononitrate placebo plus butylphthalide placebo

PLACEBO COMPARATOR

Drug: Isosorbide Mononitrate Placebo; Drug: Butylphthalide Placebo

Interventions

Isosorbide Mononitrate DRUG

Days 1-7: Isosorbide mononitrate injection, 20 mg once 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 the final week).

isosorbide mononitrate plus butylphthalide; isosorbide mononitrate plus butylphthalide placebo

Butylphthalide DRUG

Days 1-7: Butylphthalide injection, 25 mg twice daily by intravenous infusion. Days 8-6 months: Butylphthalide soft capsules, 200 mg three times daily orally.

isosorbide mononitrate placebo plus butylphthalide; isosorbide mononitrate plus butylphthalide

Isosorbide Mononitrate Placebo DRUG

Days 1-7: Isosorbide mononitrate injection placebo, once daily by intravenous infusion. Days 8-6 months: Isosorbide mononitrate sustained-release tablet placebo, once daily orally (dose reduced to half a tablet once daily during the final week).

isosorbide mononitrate placebo plus butylphthalide; isosorbide mononitrate placebo plus butylphthalide placebo

Butylphthalide Placebo DRUG

Days 1-7: Butylphthalide injection placebo, twice daily by intravenous infusion. Days 8-6 months: Butylphthalide soft capsule placebo, 2 capsules three times daily orally.

isosorbide mononitrate placebo plus butylphthalide placebo; isosorbide mononitrate plus butylphthalide placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Ischemic stroke of large artery atherosclerosis, cardioembolism, or other etiologies (TOAST classification);
• Diagnosed or suspected hereditary CSVD;
• 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.
• Previously diagnosed psychiatric disorders (DSM-5 criteria).
• 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).
• 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).
• Head trauma, intracranial or spinal surgery, major surgical procedures or severe trauma within the past 4 weeks.
• ISMN or NBP use within the past 3 days.
• Have contraindications to ISMN or NBP, or allergy to their components.
• Have to use the contraindicated drugs of this trial for a long time.
• Pregnant, breastfeeding or planning to pregnant during this study.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• Shenzhen Second People's Hospital: collaborator

MeSH Terms

Conditions

Stroke, Lacunar; Ischemic Stroke; Cerebral Small Vessel Diseases

Interventions

isosorbide-5-mononitrate; 3-n-butylphthalide

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Thrombotic Stroke; Stroke; Vascular Diseases; Cardiovascular Diseases; Brain Infarction; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Yilong Wang

  Beiling Tiantan Hospital, Capital Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Gao

CONTACT

+86 10 59976165; tjssgaoying@163.com

Yao Lu

CONTACT

+86 10 59976254; luyao970131@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 9, 2025
• First Posted: November 26, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): February 29, 2028
• Last Updated: November 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share