Sodium Valproate in Patients With Acute Ischemic Stroke

NCT ID: NCT06020898

Last Updated: 2024-02-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-01
• Study Completion Date: 2024-04-30

Brief Summary

The purpose of this pilot trial is to investigate the feasibility, safety, and efficacy of sodium valproate in patients with acute ischemic stroke, and also explore the mechanism: whether valproate increases peripheral anti-inflammatory CD177+ neutrophil levels.

Detailed Description

Ischemic stroke is one of the leading causes of disability and mortality worldwide, which imposes a huge burden on families and society. Currently, the effective treatment strategies of ischemic stroke are limited. It is of great clinical value and significance to explore effective neuroprotective medications besides reperfusion therapy.

Sodium valproate is widely used in clinical practice, and its safety and tolerability has been confirmed. It is mainly used in the treatment of epilepsy, bipolar disorder, neuropathic pain and other diseases. In recent years, a number of preclinical studies have found that valproic acid has a potential neuroprotective effect in acute ischemic brain injury, which can decrease infarct volume, reduce blood-brain barrier damage, and improve neurological function. However, the neuroprotective mechanism of sodium valproate has not been fully revealed, and there is still a lack of clinical studies to clarify the neuroprotective effect of sodium valproate in patients with ischemic stroke.

The goal of this study is to test whether sodium valproate could become a new therapeutic approach for ischemic stroke. This prospective pilot study is intended to investigate the feasibility, safety, and efficacy of sodium valproate in patients with acute ischemic stroke, thus support the estimate of sample size for a future full trial. In addition, we will test the hypotheses that valproate increases peripheral anti-inflammatory CD177+ neutrophil levels.

Patients with acute ischemic stroke included in the study will be randomly assigned to sodium valproate group (20 mg/kg/d) or saline placebo group. Treatment will be started within 24 hours after stroke onset. The trial drug will be given intravenously for 3 consecutive days. The investigators evaluate whether sodium valproate can improve clinical outcomes and increase peripheral CD177+ neutrophil levels.

Conditions

Acute Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Sodium valproate group

Within 3 days after admission, 20mg/kg sodium valproate will be given daily. Specifically, 400mg sodium valproate will be infused within 5 minutes, followed by intravenous drip with 1mg/kg/h.

Group Type: EXPERIMENTAL

Sodium valproate

Intervention Type: DRUG

Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.

Placebo group

Within 3 days after admission, normal saline will be given daily in the same way.

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.

Interventions

Sodium valproate

Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.

Intervention Type: DRUG

Normal saline

Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 18≤age<75 years;

2. Admitted to hospital within 24 hours after the onset of neurological impairment symptoms consequent to acute ischemic stroke diagnosed by CT or MRI;

3. Not suitable for thrombolysis and mechanical thrombectomy;

4. Written informed consent.

Exclusion Criteria

1. mRS ≥ 2 before the disease onset;

2. Refractory hypertension (SBP>180mmHg or DBP>110mmHg after antihypertensive treatment);

3. History of cerebral hemorrhage, intracranial tumor, cerebral arteriovenous malformation and aneurysm;

4. History of brain trauma, intracranial or spinal surgery within 3 months, major surgery or severe physical trauma within 1 month;

5. Signs of infection at time of admission;

6. History of malignancy or active autoimmune disease;

7. Use of glucocorticoids or other immunosuppressive medications;

8. Contraindications to sodium valproate: pregnancy; liver disease or severe hepatic insufficiency (ALT, AST 3 times higher than the upper normal limit); hemorrhagic risk (such as platelet count <100x109/L, APTT≥35s); allergy to sodium valproate, sodium divalproate, or valproamide; hepatic porphyria; combined use of mefloquine; mitochondrial diseases related to POLG mutations; known disorders of the urea cycle;

9. Use of medications containing active ingredients that can be converted to valproic acid, including sodium divalproate and valproamide;

10. Contraindications or intolerance for CT perfusion imaging;

11. Participating in other conflicting clinical trials;

12. Any other condition that investigators consider unsuitable such as mental illness, cognitive impairment, or inability to follow trial procedures.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Peiying Li

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peiying Li, Doctor

Role: PRINCIPAL_INVESTIGATOR

RenJi Hospital

Jieqing Wan, Doctor

Role: PRINCIPAL_INVESTIGATOR

RenJi Hospital

Locations

Renji Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Peiying Li, Doctor

Role: CONTACT

peiyingli.md@gmail.com

+8615800616866

Facility Contacts

Peiying Li, Doctor

Role: primary

peiyingli.md@gmail.com

+8615800616866

Other Identifiers

LY2023-138-A

Identifier Type: -

Identifier Source: org_study_id