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

NCT ID: NCT07252544

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 3156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-01
• Study Completion Date: 2028-02-29

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.

Detailed Description

There is an urgent need for effective therapeutic strategies for acute ischemic cerebral small vessel disease (CSVD). Isosorbide mononitrate and butylphthalide may exert protective effects; however, large-scale randomized controlled trials are required to confirm their efficacy and safety and to guide clinical practice.

In this study, patients presenting with a clinical lacunar syndrome within 7 days of onset will be randomly assigned, in a 1:1:1:1 ratio, to one of four groups in addition to routine care: (1) isosorbide mononitrate plus butylphthalide, (2) isosorbide mononitrate plus butylphthalide placebo, (3) isosorbide mononitrate placebo plus butylphthalide, or (4) isosorbide mononitrate placebo plus butylphthalide placebo. The treatment period will last 6 months, with a total follow-up of 1 year, including assessments at 7 days, 1 month, 3 months, 6 months, and 1 year.

The primary efficacy outcome is post-stroke disability at 6 months. The primary safety outcome is moderate or more severe headache within 6 months.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

isosorbide mononitrate plus butylphthalide

Group Type: EXPERIMENTAL

Isosorbide Mononitrate

Intervention Type: 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).

Butylphthalide

Intervention Type: 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 plus butylphthalide placebo

Group Type: EXPERIMENTAL

Isosorbide Mononitrate

Intervention Type: 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).

Butylphthalide Placebo

Intervention Type: 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

Group Type: EXPERIMENTAL

Butylphthalide

Intervention Type: 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

Intervention Type: 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 placebo

Group Type: PLACEBO_COMPARATOR

Isosorbide Mononitrate Placebo

Intervention Type: 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).

Butylphthalide Placebo

Intervention Type: 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.

Interventions

Isosorbide Mononitrate

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).

Intervention Type: DRUG

Butylphthalide

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.

Intervention Type: DRUG

Isosorbide Mononitrate Placebo

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).

Intervention Type: DRUG

Butylphthalide Placebo

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 30 years;

2. Clinical lacunar syndrome within 7 days;

3. Brain CT/MRI after symptom onset:

1. a relevant (in time and location) acute lacunar infarct;

2. 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:

1. MoCA ≥ 13 if educated ≤ 6 years;

2. MoCA ≥ 15 if 7 ≤ educated ≤ 12 years;

3. MoCA ≥ 18 if educated ≥ 13 years；

5. mRS ≤ 1 prior to this episode;

6. Patient or a legally authorized representative signed informed consent.

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.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Second People's Hospital

OTHER

Sponsor Role: collaborator

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

yilong Wang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yilong Wang

Role: PRINCIPAL_INVESTIGATOR

Beiling Tiantan Hospital, Capital Medical University

Central Contacts

Ying Gao

Role: CONTACT

tjssgaoying@163.com

+86 10 59976165

Yao Lu

Role: CONTACT

luyao970131@163.com

+86 10 59976254

Other Identifiers

2023ZD0504802

Identifier Type: -

Identifier Source: org_study_id