Chronic Stable Angina
Conditions
Keywords
Green tea polyphenols, Chronic Stable Angina
Brief summary
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
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.
Interventions
DRUGSTA-2
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.
DRUGPlacebo
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.
Sponsors
Sinphar Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged \> 20; 2. 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; 3. 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); 4. 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; 5. 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; 6. Able to provide written informed consent.
Exclusion criteria
1. Patients with pre-excitation, conduction abnormalities, pacemaker rhythm, unstable angina or myocardial infarction within the preceding 3 months; 2. 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; 3. Patients with any EKG abnormalities preventing the interpretation of ischemia (complete left bundle branch block); 4. Patients with Chronic Obstructive Pulmonary Disease (COPD) requiring bronchodilators; 5. 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); 6. Patients with severe gastrointestinal illness as judged by the investigator; 7. Patient with any conditions that interfered the performance of exercise tolerance test as judged by investigator (e.g., knee/ankle arthropathy, Parkinsonism, stroke).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Exercise Time | baseline (visit 2) and week 6 (visit 5) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Time to 1mm ST-segment Depression During Exercise Tolerance Testing (ETT). | baseline (visit 2) through week 6 (visit 5) | 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. |
| Change in Consumption of Short-acting Nitrates | from baseline (visit 2) through week 6 (visit 5) | 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. |
| Change in Rate-pressure Product | baseline (visit 2) to week 6 (visit 5) | 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. |
| Change in Pharmacological Parameters | baseline (visit 2) to week 6 (visit 5) | 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. |
| 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. | — |
Countries
Taiwan
Participant flow
Recruitment details
First Patient Enrolled: May-10-2007 Last Patient Completed: Jun-17-2008
Pre-assignment details
Patients underwent one-week screening and washout period prior to randomization
Participants by arm
| Arm | Count |
|---|---|
| STA-2 STA-2 250 mg capsule, each containing 100 mg green tea polyphenols.
Two capsules three times daily for 6 weeks, to be administered in a non-fasting state. | 39 |
| Placebo Placebo capsule, containing non-active ingredients.
Two capsules three times daily for 6 weeks, to be administered in a non-fasting state. | 40 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | STA-2 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 16 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 24 Participants | 48 Participants |
| Region of Enrollment Taiwan | 39 participants | 40 participants | 79 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Male | 34 Participants | 32 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / — | 0 / — |
| serious Total, serious adverse events | 0 / — | 1 / — |
Outcome results
Primary
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.
Time frame: baseline (visit 2) and week 6 (visit 5)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| STA-2 | Change in Total Exercise Time | 450.39 seconds | Standard Deviation 106.7 |
| Placebo | Change in Total Exercise Time | 411.15 seconds | Standard Deviation 118.1 |
Comparison: T-test was used to compare the change in total exercise time between the treatment groups. The change in total exercise time (△) was defined as the total exercise time at end-point visit minus the total exercise time at baseline. Let △T be the change in total exercise time for treatment group (STA-2) and △C be the change in total exercise time for control group (Placebo). The hypothesis testing for the superiority of STA-2 to Placebo was H0：△T-△C≦0 with H1：△T-△C﹥0.p-value: 0.025t-test, 1 sided
Secondary
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.
Time frame: from baseline (visit 2) through week 6 (visit 5)
Secondary
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.
Time frame: baseline (visit 2) to week 6 (visit 5)
Secondary
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.
Time frame: baseline (visit 2) to week 6 (visit 5)
Secondary
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.
Time frame: baseline (visit 2) through week 6 (visit 5)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| STA-2 | Changes in Time to 1mm ST-segment Depression During Exercise Tolerance Testing (ETT). | 396.76 seconds | Standard Deviation 109 |
| Placebo | Changes in Time to 1mm ST-segment Depression During Exercise Tolerance Testing (ETT). | 341.69 seconds | Standard Deviation 138.5 |
Comparison: All hypothesis testing was conducted with T-tests, two sides at 0.05 significance level and 95% Confidence Interval (C.I.) was adopted if needed.p-value: 0.005t-test, 2 sided
Secondary
Consumption of Short-acting Nitrates
Time frame: 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.
Population: The data was not available for analysis, because only two patients administered short-acting nitrates