DLBS1033 for Acute Ischemic Stroke Patients

Study Overview
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Brief Summary
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This is a prospective, randomized, double-blind, and controlled clinical study to investigate the effects of DLBS1033 in conjunction with standard therapy compared to standard therapy alone in acute ischemic stroke patients. It is hypothesized that the improvement in functional outcomes as measured by NIHSS and BI as well as the improvement in haemostatic parameters as measured by thrombocyte aggregation test (TAT), fibrinogen, and d-dimer in DLBS group will be significantly greater than those in the control group.

Detailed Description
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Subjects in this study will be screened consecutively and eligible subjects will be randomized into two groups and receive the investigational drug, DLBS1033 at a dose of 490 mg three times daily or its placebo in addition to standard therapy for 28-days course of therapy. Standard therapy used in this study will consist of: aspirin 80 mg, simvastatin 20 mg, and vitamin B complex. After hospital admission and diagnosis, patient will be handled as per acute ischemic stroke management in each study site. Right after the patient is confirmed eligible to the study, the treatment(s) will be switched immediately into the study treatments. Clinical and laboratory examinations to evaluate the investigational drug's efficacy will be performed at baseline and 3, 7,14, and 28 days after study medication initiation; while safety examinations will be performed at the same time point, but 3 and 14 days after study medication initiation.

Official Title
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Addition of DLBS1033 to Standard Therapy for Acute Ischemic Stroke Patients

Conditions
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Acute Ischemic Stroke, Partial Anterior Circulation Infarct, Lacunar Anterior Circulation Infarct

Intervention / Treatment
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* Drug: DLBS1033
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent from the patients or patients' legally acceptable representatives (must be obtained before any trial related activities). Male or female subjects with age of >18 years at Screening. Patients clinically diagnosed having acute ischemic stroke attack and confirmed by CT scan. Patients with cerebral infarction subtypes of PACI or LACI as classified by Bamford criteria. Patients with moderate condition based on National Institutes of Health Stroke Scale (NIHSS) score of 5-15. Patients present at hospital and receiving first dose of study medication within 72 hours after the onset of the stroke symptoms. Able to take oral medication. Exclusion Criteria: For females of childbearing potential: pregnancy and lactation period. History of hemorrhagic stroke within the last 3 months. Patients with seizure at the onset of stroke or with regular medication for seizure/epilepsy. Current or regular use (within the last 1 month) of oral anticoagulants, antiplatelets other than study medication, and herbal medicines. Patients who have received tissue plasminogen activator (TPA) within 24 hours to Screening. History of serious head injury within the last 3 months. History of major surgery within the last 3 months. Recent serious cardiovascular conditions, such as myocardial infarction and heart atrial fibrillation as demonstrated by electrocardiography (ECG). History of congestive heart failure and aortic dissection. Presence of severe renal and hepatic dysfunction, defined as serum creatinine level > 3x upper limit of normal (ULN) or history of hemodialysis, and any of serum ALT, AST, Gamma-GT level of > 3x ULN, respectively. Presence of acute SIRS. Presence of chronic infections. Patients with higher risks of bleeding. Subjects with uncontrolled hypertension (systolic blood pressure > 185 mmHg or diastolic blood pressure > 110 mmHg). Subjects with random plasma glucose ≥180 mg/dL and HbA1c ≥ 7.0% at Screening. Known or suspected hypersensitivity to the trial product or related products. Participation in any other clinical studies within 30 days prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo 3 x 1 tablet, given everyday for 28 days of study period | Drug: Placebo<br>* Investigational drug or placebo will be given in addition to the standard therapy, consists of: aspirin enteric-coated tablet 1 x 80 mg daily, simvastatin film-coated tablet 1 x 20 mg daily, and vitamin B complex 1 x 1 tablet<br>|
| Experimental: DLBS1033<br>DLBS1033 enteric-coated tablet 3 x 490 mg daily, given everyday for 28 days of study period | Drug: DLBS1033<br>* Investigational drug or placebo will be given in addition to the standard therapy, consists of: aspirin enteric-coated tablet 1 x 80 mg daily, simvastatin film-coated tablet 1 x 20 mg daily, and vitamin B complex 1 x 1 tablet<br>* Other names: Disolf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale (NIHSS) | Change in functional outcomes as measured by NIHSS from its baseline value | 3, 7, 14, and 28 days after study medication | 
| Barthel Index (BI) | Change in functional outcomes as measured by BI from its baseline value | 3, 7, 14, and 28 days after study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thrombocyte Aggregation Test (TAT) | Change in haemostatic parameter as measured by TAT from its baseline value | 3, 7, 14, and 28 days after study medication | 
| Fibrinogen level | Change in haemostatic parameter as measured by fibrinogen level from its baseline value | 3, 7, 14, and 28 days after study medication | 
| D-dimer level | Change in haemostatic parameter as measured by d-dimer level from its baseline value | 3, 7, 14, and 28 days after study medication | 
| Liver function | Liver function measured includes: serum AST, ALT, gamma-GT, total bilirubin | 7 and 28 days after study medication | 
| Renal function | Renal function measured includes: serum creatinine | 7 and 28 days after study medication | 
| Routine hematology | Routine hematology measured includes: hemoglobin, hematocrit, RBC, WBC, differentiation of WBC, and platelet count | 7 and 28 days after study medication | 
| Adverse events | Adverse events, including bleeding events, will be observed and carefully evaluated along the course of the study | 1 - 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBS1033, Acute ischemic stroke, NIHSS, Barthel Index