DLBS1033 Treatment in Diabetic With Peripheral Arterial Disease

Study Overview
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Brief Summary
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This is a prospective, randomized, double-blind, double-dummy, and controlled study of DLBS1033 for the improvement of ankle-brachial index in diabetic patients with peripheral arterial disease (PAD). It is hypothesized that the addition of DLBS1033 on top of aspirin treatment will augment significantly the resting ABI in diabetes patient with PAD in comparison with that of aspirin alone.

Detailed Description
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Subjects in this study will be screened consecutively and eligible subjects will be randomized to receive aspirin tablet 80 mg once daily and either the investigational drug (DLBS1033 tablet 490 mg three times daily) or its placebo, for 12 weeks. Diabetic subjects who have been being under therapy with aspirin can directly start with study treatment. For those who are currently not under therapy with aspirin, there will be a run-in period during which they will receive (or be switched to) aspirin treatment, for two weeks. After then, they will receive study medication. Clinical and laboratory examinations to evaluate the investigational drug's efficacy and safety will be performed at baseline and at the interval of six weeks over the twelve week-course of therapy.

Official Title
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Improvement of Ankle-Brachial Index by DLBS1033 Treatment in Diabetic Patients With Peripheral Arterial Disease

Conditions
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Diabetes, Peripheral Arterial Disease

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 before any trial related activities. Male or female subjects of 40 - 65 years of age. Diagnosis of diabetes mellitus defined as HbA1c level of ≥ 6.5% (for newly diagnosed diabetes) or based on medical history. Presence of peripheral arterial disease with resting ankle-brachial index (ABI) of 0.41-0.90 inclusive Exclusion Criteria: Females of childbearing potential: pregnancy, breast-feeding, and the intention of becoming pregnant. Recent stroke attack, myocardial infarction/unstable angina/acute coronary syndrome, coronary artery bypass surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA)/stent within 3 (three) months prior to screening. Impaired liver function: serum ALT > 2.5 times upper limit of normal. Impaired renal function: serum creatinine ≥ 1.5 times upper limit of normal. Concomitant use of other antithrombosis drugs or any antiplatelets other than the study medication. Subjects with concurrent herbal (alternative) medicines or food supplements Subjects with any other disease state, including chronic or acute systemic infections, uncontrolled illnesses or other chronic diseases, which judged by the investigator, could interfere with trial participation or trial evaluation. Subjects with high risk of bleeding: Subjects with prior experience with DLBS1033 or other oral lumbrokinase products. Subjects with known or suspected allergy to any of study medications used in the study, including other lumbrokinase products. Subjects with known or suspected allergy or resistant to aspirin.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: DLBS1033<br>DLBS1033 tablet is administered at the dose of 490 mg, one tablet three times daily, every day for twelve weeks of study period | Drug: DLBS1033<br>* Investigational drug or placebo will be given in addition to the standard therapy: aspirin at the dose of 80 mg, once daily, every day for twelve weeks of study period<br>* Other names: Disolf;|
| Placebo Comparator: Placebo<br>Placebo tablet is administered one tablet three times daily, every day for twelve weeks of study period | Drug: Placebo<br>* Investigational drug or placebo will be given in addition to the standard therapy: aspirin at the dose of 80 mg, once daily, every day for twelve weeks of study period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting ankle-brachial index (ABI) | The change of resting ABI | Week 0 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting ABI | The change of resting ABI | Week 0 and 6 | 
| hs-CRP | The change of hs-CRP | Week 0, 6, and 12 | 
| Thromboxane B2 | The change of thromboxane B2 | Week 0, 6, and 12 | 
| Fibrinogen | The change of fibrinogen | Week 0, 6, and 12 | 
| d-dimer | The change of d-dimer | Week 0, 6, and 12 | 
| Routine hematology | Routine hematology measured includes: hemoglobin, hematocrit, RBC, WBC, differentiation of WBC, and platelet count | Week 0, 6, and 12 | 
| Liver function | Liver function measured includes: serum ALT, AST, and alkaline phosphatase | Week 0 and 12 | 
| Renal function | Renal function measured includes: serum creatinine and blood urea nitrogen (BUN) | Week 0 and 12 | 
| Haemostasis parameters | Haemostasis parameters measured includes: prothrombin time (PT) and activated partial thromboplastin time (aPTT) | Week 0, 6, and 12 | 
| Adverse events | Adverse events, including bleeding events, will be observed and carefully evaluated along the course of the study | Week 0 - 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBS1033, Peripheral arterial disease, Ankle-brachial index