Phase II Study of STA-2 in Patients With Chronic Stable Angina

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the efficacy, pharmacological activities and safety of STA-2 in the treatment of chronic stable angina.

Detailed Description
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The primary objective of this study was to evaluate the efficacy of STA-2 in the management of chronic stable angina. The secondary objectives of this study were to evaluate the safety and pharmacological activities of STA-2 in the management of chronic stable angina. This was a multi-center, double-blind, randomized, parallel-group, placebo-controlled study of STA-2 in the management of chronic stable angina. The study period for each patient was approximately 7 weeks, during which the patient undergone one-week screening and washout period, followed by 6 weeks of treatment. Each patient was required to make a total of 5 visits. Primary Efficacy Endpoint: Change in total exercise time. After washout, patients who met the inclusion and exclusion criteria were randomly assigned either to the treatment or control group. The respective regimens were: Treatment group: STA-2 250 mg capsule, each containing 100 mg green tea polyphenols, 2 capsules ter in die (t.i.d.=three times daily) for 6 weeks, to be administered in a non-fasting state. Control group: Placebo 250 mg capsule, 2 capsules t.i.d. (three times daily) for 6 weeks, to be administered in a non-fasting state.

Official Title
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A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of STA-2 in Patients With Chronic Stable Angina

Conditions
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Chronic Stable Angina

Intervention / Treatment
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* Drug: STA-2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female aged > 20; Patients who had effort-induced angina which was relieved by rest or nitroglycerin, or who had catheterization-documented coronary artery disease or previous myocardial infarction ≥ 3 months before screening; Patients who manifested positive ETT (exercise tolerance testing) (defined as ST-segment depression ≥ 1 mm compared with at rest, with or without limiting angina) at screening (Day -7); Patients who manifested positive ETT (exercise tolerance testing) (defined as ST-segment depression ≥ 1 mm compared with at rest, with or without limiting angina) on the day of enrollment (Day 0). ETT performance between Day -7 and Day 0 were required not differ by >20% in total exercise time; Female patient who was in the post-menopausal stage or of childbearing potential who: used adequate contraception since last menstruation and no plan for conception during the study; was non-lactating; had negative pregnancy test (urine) within 14 days prior to the study; Able to provide written informed consent. Exclusion criteria: Patients with pre-excitation, conduction abnormalities, pacemaker rhythm, unstable angina or myocardial infarction within the preceding 3 months; Patients with heart failure (New York Heart Association class III or IV), uncorrected valvular or congenital heart disease, patients who needed digoxin, isosorbide mononitrate, nitroglycerin sustained release preparation, theophylline, class I antiarrhythmic agents, digitalis, or monoamine oxidase inhibitors, as judged by the investigator; Patients with any EKG abnormalities preventing the interpretation of ischemia (complete left bundle branch block); Patients with Chronic Obstructive Pulmonary Disease (COPD) requiring bronchodilators; Patients with hepatic failure (defined as aspartate transaminase (AST) and/or alanine transaminase (ALT) > 3X the upper limit of normal values), and/or renal failure (defined as serum creatinine > 3 mg/dL); Patients with severe gastrointestinal illness as judged by the investigator; Patient with any conditions that interfered the performance of exercise tolerance test as judged by investigator (e.g., knee/ankle arthropathy, Parkinsonism, stroke).

Ages Eligible for Study
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Minimum Age: 20 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STA-2<br>STA-2 250 mg capsule, each containing 100 mg green tea polyphenols. Two capsules t.i.d. (three times daily) for 6 weeks, to be administered in a non-fasting state. | Drug: STA-2<br>* After 1 week of screening and washout, patients who met the entry criteria were randomly assigned either to the treatment or control group. The regimen of STA-2 was: STA-2 250 mg capsule, each containing 100 mg green tea polyphenols, 2 capsules t.i.d. (three times a day) for 6 weeks, to be administered in a non-fasting state.<br>|
| Placebo Comparator: Placebo<br>Placebo capsule, containing non-active ingredients. Two capsules t.i.d. (three times daily) for 6 weeks, to be administered in a non-fasting state. | Drug: Placebo<br>* After 1 week of screening and washout, patients who met the entry criteria were randomly assigned either to the treatment or control group. The regimen of Placebo was: Placebo 250 mg capsule, 2 capsules t.i.d. (three times a day) for 6 weeks, to be administered in a non-fasting state.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Exercise Time | Total exercise time was defined as the maximal duration of exercise which was performed by the patient in the setting of exercise tolerance tests (ETT). A 12-lead electrocardiogram (EKG) was used to continuously monitor vital signs. Patients were asked to complete 9-12 minutes of exercise or to exercise until 85% of the maximum predicted heart rate was reached. All exercise tolerance tests used a standard Bruce multistage exercise test protocol. | baseline (visit 2) and week 6 (visit 5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Time to 1mm ST-segment Depression During Exercise Tolerance Testing (ETT). | Time to 1 millimeter (mm) ST-segment depression was recorded from Electrocardiogram (EKG) during exercise tolerance testing (ETT). The 1mm ST-segment depression may be seen in typical angina patient. It means the ST segment of EKG wave drops at least 1 mm compared to the beginning of EKG measurement. | baseline (visit 2) through week 6 (visit 5) | 
| Change in Consumption of Short-acting Nitrates | The consumption of short-acting nitrates from baseline (V2, Day 0) to all visits [V3 (Day 14±2), V4 (Day 28±2), V5 (Day 42±2)]according to patient's diary. | from baseline (visit 2) through week 6 (visit 5) | 
| Change in Rate-pressure Product | Rate-pressure product was defined as the product of heart rate and systolic blood pressure, which was measured both at rest and at peak of exercise. | baseline (visit 2) to week 6 (visit 5) | 
| Change in Pharmacological Parameters | The level of oxidative stress parameters (isoprostane, homocysteine), homeostasis parameters (PAI-I activity), inflammatory markers (fibrinogen, hsCRP, soluble CD40 ligand) and cardiac enzymes (CPK-MB and LDH), were measured to assess the pharmacological activity of STA-2. | baseline (visit 2) to week 6 (visit 5) | 
| Consumption of Short-acting Nitrates |  | The consumption of short-acting nitrates from baseline (V2, Day 0) to all visits [V3 (Day 14±2), V4 (Day 28±2), V5 (Day 42±2)]according to patient's diary. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Green tea polyphenols, Chronic Stable Angina