Coronary Disease, Stable Angina
Conditions
Keywords
Nicorandil, Stable angina
Brief summary
This study of 402 cases of stable angina subjects who were diagnosed as Coronary Heart Disease (CHD) is a randomized, blank controlled, multi-center clinical study. Subjects who are taking standard treatment with stable symptoms will receive a 24-hour ambulatory electrocardiogram (ECG) (Holter) examination. They will be randomly divided into two groups. The nicorandil group will receive nicorandil 5 milligram (mg) (3 times a day = tid) on top of the standard treatment for 12 weeks, while the control group will stay on standard treatment. Nitrates and beta blockers need to be maintained on a stable dose. Other drugs that do not affect the primary endpoint may be adjusted per investigators decision.
Interventions
DRUGNicorandil
The subjects will receive Nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with the standard treatment.
DRUGStandard Treatment
The subjects will receive one of the standard anti-anginal therapies which included but not limited to aspirin, ACEI, lipid lowering statins and beta blockers according to the recommendation of guidelines. If the subject's condition permitted, they should take all these medicines. However, the dose, route, frequency and duration were determined by investigators according to subject's specific condition.
Sponsors
Merck Serono Co., Ltd., China
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject must be diagnosed as stable CHD, and must have at least one of these histories: 1. A history of coronary revascularization Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Surgery at least 3 months ago 2. Myocardial infarction 3. More than 50 percent (%) stenosis detected by angiography 4. Exercise Tolerance Testing (ETT) or Computed Tomography Angiography (CTA) showed more than 50% stenosis with typical angina symptoms * Subjects must have at least 2 times of typical symptoms of myocardial ischemia occurred within a week Other protocol defined inclusion criteria could apply
Exclusion criteria
* Coronary syndrome or considering acute coronary syndrome (ACS) * Left main coronary artery disease without revascularization * Aortic stenosis * Obstructive hypertrophic cardiomyopathy * Subjects with hypertension systolic blood pressure (SBP) greater than (\>) 170 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) \>100 mmHg) or hypotension (SBP less than \[\<\] 90 mmHg or DBP\<60 mmHg) * Diagnosis as postural hypotension before * Congestive heart failure (New York Heart Association \[NYHA\] class III - IV * Ejection fraction (EF)\<40% by Echocardiography * Arrhythmias requiring active treatment * Gastro-intestinal ulcer * Concomitant medication such as Sulphonyl urea, PDE-5 inhibitor such as sildenafil, Trimetazidine for treatment of angina pectoris Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Myocardial Ischemia Attacks in 24 Hours | At Week 12 | Myocardial ischemia attack was evaluated by 24-hour Holter monitoring based on the following criteria: 0.08 seconds after the J point in electrocardiogram (ECG) or compared with baseline levels, ST-segment with horizontal or downward sloping down greater than or equal to (\>=) 0.1 millivolts (mV), and lasted for \>= 1 minute, and at least 1 minute of interval with another ischemic attack, as one array myocardial ischemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maximum ST-depression at Week 12 | Baseline, Week 12 | The maximum ST- depression was evaluated from sum of all leads for all the subjects with myocardial ischemia attack. Absolute value of maximum ST-depression was used for calculation. |
| Change From Baseline in Longest Duration of ST Segment Depression at Week 12 | Baseline, Week 12 | The maximum ST- depression was evaluated from sum of all leads for all the subjects with myocardial ischemia attack. The longest duration of ST segment depression of all leads for all the subjects with myocardial ischemia attack. |
| Percentage of Subjects Experienced Ischemic Heart Attack During the Six-minute Walk Test | At Week 12 | The percentage of subjects who experienced ischemic heart attack during the Six-minute walk test (6-MWT) were evaluated.The 6-MWT was the distance that a subject could walk in 6 minutes. Subjects were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. The 6-MWT was completed within 1-hour after wearing Holter. |
| Heart Rate Variability (HRV) Rate: Time Domain | At Week 12 | HRV is the degree of fluctuation in the length of the intervals between heart beats. All HRV parameters are calculated on 'normal-to-normal' (NN) inter-beat intervals (or NN intervals) caused by normal heart contractions. Standard deviation of all NN intervals (SDNN) and Standard deviation of the averages of NN intervals (SDANN) are the two time domain methods used to determine heart rate variability. Two variants of the SDNN, created by dividing the 24-hour monitoring period into 5-minute segments, are the SDNN index and the SDANN index. The SDNN index is the mean of all the 5-minute standard deviations of NN (normal RR) intervals during the 24-hour period, while the SDANN index is the standard deviation of all the 5-minute NN interval means. |
| Heart Rate Variability (HRV) Rate: Frequency Domain Power-24 Hour | At Week 12 | HRV is the degree of fluctuation in the length of the intervals between heart beats. All HRV parameters are calculated on 'normal-to-normal' (NN) inter-beat intervals (or NN intervals) caused by normal heart contractions. The HRV was evaluated based on frequency domain power-24 hours. |
| Number of Arrhythmia Occurred Within 24 Hours | At Week 12 | The number of ventricular tachycardia and premature ventricular beats that occurred within 24 hours. |
| ECG QT Dispersion | At Week 12 | The ECG QT dispersion was defined as the difference between the longest (QTmax) and the shortest (QTmin) QT intervals within a 12-lead ECG. |
| Change From Baseline in Total Myocardial Ischemic Burden at Week 12 | Baseline, Week 12 | The total myocardial ischemic burden was defined as the product of the decrease, total array and total time of ST-segment in symptomatic and asymptomatic myocardial ischemia subjects within 24 hours. |
| Frequency of Angina Attack | At Week 12 | The total number of times angina attacks occurred within a week (number of times/week) |
| Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin | At Week 12 | — |
| Number of Nitroglycerin Tablets Consumed in a Week | At Week 12 | — |
| Walk Distance in Six Minute Walk (6-MWT) Test at Week 12 | At Week 12 | The 6-MWT distance was the distance that a subject could walk in 6 minutes. Subjects were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. The 6-MWT was completed within 1-hour after wearing Holter. |
| Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation | From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ) | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Subjects Who Showed Compliance to Nicorandil | Baseline up to 12 Weeks | Compliance percent (%) was calculated by using the formula: (actual total dose divided by planned total dose) multiplied by 100. If subject compliance was less than 80% or greater than 120%, then that subject was considered as non compliant. The compliance of subjects taking nicorandil was evaluated. |
| Number of Subjects Experienced Angina Attack | Baseline up to 12 Weeks | — |
Countries
China
Participant flow
Pre-assignment details
4 subjects randomized to standard+nicorandil group were included in standard group for safety analysis as they did not receive nicorandil. 1 subject randomized to standard group was included in standard+nicorandil group as nicorandil was received. Thus, safety set have 197 and 205 in Standard+nicorandil and standard group, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Standard Treatment Plus Nicorandil The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies ( aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators. | 200 |
| Standard Treatment The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators. | 202 |
| Total | 402 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 2 |
| Overall Study | Lost to Follow-up | 17 | 11 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 12 |
Baseline characteristics
| Characteristic | Standard Treatment Plus Nicorandil | Standard Treatment | Total |
|---|---|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 10.16 | 60.8 years STANDARD_DEVIATION 9.94 | 61.1 years STANDARD_DEVIATION 10.04 |
| Sex: Female, Male Female | 58 Participants | 74 Participants | 132 Participants |
| Sex: Female, Male Male | 142 Participants | 128 Participants | 270 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 197 | 1 / 205 |
| serious Total, serious adverse events | 9 / 197 | 7 / 205 |
Outcome results
Primary
Number of Myocardial Ischemia Attacks in 24 Hours
Myocardial ischemia attack was evaluated by 24-hour Holter monitoring based on the following criteria: 0.08 seconds after the J point in electrocardiogram (ECG) or compared with baseline levels, ST-segment with horizontal or downward sloping down greater than or equal to (\>=) 0.1 millivolts (mV), and lasted for \>= 1 minute, and at least 1 minute of interval with another ischemic attack, as one array myocardial ischemia.
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Treatment Plus Nicorandil | Number of Myocardial Ischemia Attacks in 24 Hours | 2.3 ischemic attacks per 24 hours | Standard Deviation 8.46 |
| Standard Treatment | Number of Myocardial Ischemia Attacks in 24 Hours | 3.8 ischemic attacks per 24 hours | Standard Deviation 18.02 |
p-value: =0.008695% CI: [0.301, 0.84]Poisson regression: Calibration model
p-value: <0.000195% CI: [0.435, 0.581]poisson regression: Non-calibration mode
Secondary
Change From Baseline in Longest Duration of ST Segment Depression at Week 12
The maximum ST- depression was evaluated from sum of all leads for all the subjects with myocardial ischemia attack. The longest duration of ST segment depression of all leads for all the subjects with myocardial ischemia attack.
Time frame: Baseline, Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure. Analysis was done only for subjects with myocardial ischemia attack.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Treatment Plus Nicorandil | Change From Baseline in Longest Duration of ST Segment Depression at Week 12 | -3.8 seconds | Standard Deviation 37.75 |
| Standard Treatment | Change From Baseline in Longest Duration of ST Segment Depression at Week 12 | 3.4 seconds | Standard Deviation 18.83 |
Secondary
Change From Baseline in Maximum ST-depression at Week 12
The maximum ST- depression was evaluated from sum of all leads for all the subjects with myocardial ischemia attack. Absolute value of maximum ST-depression was used for calculation.
Time frame: Baseline, Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure. Analysis was done only for subjects with myocardial ischemia attack.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Treatment Plus Nicorandil | Change From Baseline in Maximum ST-depression at Week 12 | 0.25 millimeter | Standard Deviation 3.598 |
| Standard Treatment | Change From Baseline in Maximum ST-depression at Week 12 | 0.36 millimeter | Standard Deviation 3.563 |
Secondary
Change From Baseline in Total Myocardial Ischemic Burden at Week 12
The total myocardial ischemic burden was defined as the product of the decrease, total array and total time of ST-segment in symptomatic and asymptomatic myocardial ischemia subjects within 24 hours.
Time frame: Baseline, Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure. Analysis was done only for subjects with myocardial ischemia attack.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Treatment Plus Nicorandil | Change From Baseline in Total Myocardial Ischemic Burden at Week 12 | -38.63 millimeter*minutes | Standard Deviation 572.807 |
| Standard Treatment | Change From Baseline in Total Myocardial Ischemic Burden at Week 12 | 29.26 millimeter*minutes | Standard Deviation 404.07 |
Secondary
ECG QT Dispersion
The ECG QT dispersion was defined as the difference between the longest (QTmax) and the shortest (QTmin) QT intervals within a 12-lead ECG.
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Treatment Plus Nicorandil | ECG QT Dispersion | 0.1298 milliseconds | Standard Deviation 0.1724 |
| Standard Treatment | ECG QT Dispersion | 0.1110 milliseconds | Standard Deviation 0.15865 |
Secondary
Frequency of Angina Attack
The total number of times angina attacks occurred within a week (number of times/week)
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Treatment Plus Nicorandil | Frequency of Angina Attack | 1 angina attacks per week |
| Standard Treatment | Frequency of Angina Attack | 2 angina attacks per week |
Secondary
Heart Rate Variability (HRV) Rate: Frequency Domain Power-24 Hour
HRV is the degree of fluctuation in the length of the intervals between heart beats. All HRV parameters are calculated on 'normal-to-normal' (NN) inter-beat intervals (or NN intervals) caused by normal heart contractions. The HRV was evaluated based on frequency domain power-24 hours.
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Treatment Plus Nicorandil | Heart Rate Variability (HRV) Rate: Frequency Domain Power-24 Hour | 2397.0 millisecond square (ms^2) | Standard Deviation 1527.37 |
| Standard Treatment | Heart Rate Variability (HRV) Rate: Frequency Domain Power-24 Hour | 2328.6 millisecond square (ms^2) | Standard Deviation 1458.31 |
Secondary
Heart Rate Variability (HRV) Rate: Time Domain
HRV is the degree of fluctuation in the length of the intervals between heart beats. All HRV parameters are calculated on 'normal-to-normal' (NN) inter-beat intervals (or NN intervals) caused by normal heart contractions. Standard deviation of all NN intervals (SDNN) and Standard deviation of the averages of NN intervals (SDANN) are the two time domain methods used to determine heart rate variability. Two variants of the SDNN, created by dividing the 24-hour monitoring period into 5-minute segments, are the SDNN index and the SDANN index. The SDNN index is the mean of all the 5-minute standard deviations of NN (normal RR) intervals during the 24-hour period, while the SDANN index is the standard deviation of all the 5-minute NN interval means.
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. n signifies the number of subjects evaluable for each category in each group for this outcome measure, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Treatment Plus Nicorandil | Heart Rate Variability (HRV) Rate: Time Domain | SDNN-24 hour (n=141, 149) | 126.1 millisecond | Standard Deviation 35.58 |
| Standard Treatment Plus Nicorandil | Heart Rate Variability (HRV) Rate: Time Domain | SDANN index (n=141, 149) | 116.9 millisecond | Standard Deviation 37.44 |
| Standard Treatment Plus Nicorandil | Heart Rate Variability (HRV) Rate: Time Domain | SDNN index (n=140, 147) | 47.6 millisecond | Standard Deviation 14.6 |
| Standard Treatment | Heart Rate Variability (HRV) Rate: Time Domain | SDNN-24 hour (n=141, 149) | 125.7 millisecond | Standard Deviation 33.25 |
| Standard Treatment | Heart Rate Variability (HRV) Rate: Time Domain | SDANN index (n=141, 149) | 116.7 millisecond | Standard Deviation 33.65 |
| Standard Treatment | Heart Rate Variability (HRV) Rate: Time Domain | SDNN index (n=140, 147) | 47.0 millisecond | Standard Deviation 14.99 |
Secondary
Number of Arrhythmia Occurred Within 24 Hours
The number of ventricular tachycardia and premature ventricular beats that occurred within 24 hours.
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Treatment Plus Nicorandil | Number of Arrhythmia Occurred Within 24 Hours | Ventricular tachycardia | 0.8 beats per 24 hours | Standard Deviation 4.03 |
| Standard Treatment Plus Nicorandil | Number of Arrhythmia Occurred Within 24 Hours | Premature ventricular beat | 134.8 beats per 24 hours | Standard Deviation 457.59 |
| Standard Treatment | Number of Arrhythmia Occurred Within 24 Hours | Ventricular tachycardia | 5.2 beats per 24 hours | Standard Deviation 40.67 |
| Standard Treatment | Number of Arrhythmia Occurred Within 24 Hours | Premature ventricular beat | 569.1 beats per 24 hours | Standard Deviation 2538.17 |
Secondary
Number of Nitroglycerin Tablets Consumed in a Week
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Treatment Plus Nicorandil | Number of Nitroglycerin Tablets Consumed in a Week | 1 tablets per week |
| Standard Treatment | Number of Nitroglycerin Tablets Consumed in a Week | 2 tablets per week |
Secondary
Number of Subjects Experienced Angina Attack
Time frame: Baseline up to 12 Weeks
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Treatment Plus Nicorandil | Number of Subjects Experienced Angina Attack | 48 subjects |
| Standard Treatment | Number of Subjects Experienced Angina Attack | 70 subjects |
Secondary
Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Treatment Plus Nicorandil | Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin | 20 subjects |
| Standard Treatment | Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin | 43 subjects |
Secondary
Number of Subjects Who Showed Compliance to Nicorandil
Compliance percent (%) was calculated by using the formula: (actual total dose divided by planned total dose) multiplied by 100. If subject compliance was less than 80% or greater than 120%, then that subject was considered as non compliant. The compliance of subjects taking nicorandil was evaluated.
Time frame: Baseline up to 12 Weeks
Population: Safety analysis population included all the subjects who received at least one dose of the study drug. 4 subjects randomized to standard+nicorandil group were included in standard group for safety analysis as they did not receive nicorandil. 1 subject randomized to standard group was included in standard+nicorandil group as nicorandil was received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Treatment Plus Nicorandil | Number of Subjects Who Showed Compliance to Nicorandil | 181 subjects |
Secondary
Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks )
Population: Safety analysis population included all the subjects who received at least one dose of the study drug. 4 subjects randomized to standard+nicorandil group were included in standard group for safety analysis as they did not receive nicorandil. 1 subject randomized to standard group was included in standard+nicorandil group as nicorandil was received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Treatment Plus Nicorandil | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation | TEAEs | 23 subjects |
| Standard Treatment Plus Nicorandil | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation | SAEs | 9 subjects |
| Standard Treatment Plus Nicorandil | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation | AEs Leading to Death | 1 subjects |
| Standard Treatment Plus Nicorandil | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 16 subjects |
| Standard Treatment | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 subjects |
| Standard Treatment | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation | TEAEs | 13 subjects |
| Standard Treatment | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation | AEs Leading to Death | 1 subjects |
| Standard Treatment | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation | SAEs | 7 subjects |
Secondary
Percentage of Subjects Experienced Ischemic Heart Attack During the Six-minute Walk Test
The percentage of subjects who experienced ischemic heart attack during the Six-minute walk test (6-MWT) were evaluated.The 6-MWT was the distance that a subject could walk in 6 minutes. Subjects were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. The 6-MWT was completed within 1-hour after wearing Holter.
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure. Analysis was done only for subjects with myocardial ischemia attack.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Treatment Plus Nicorandil | Percentage of Subjects Experienced Ischemic Heart Attack During the Six-minute Walk Test | 2.2 percentage of subjects |
| Standard Treatment | Percentage of Subjects Experienced Ischemic Heart Attack During the Six-minute Walk Test | 4.1 percentage of subjects |
Secondary
Walk Distance in Six Minute Walk (6-MWT) Test at Week 12
The 6-MWT distance was the distance that a subject could walk in 6 minutes. Subjects were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. The 6-MWT was completed within 1-hour after wearing Holter.
Time frame: At Week 12
Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Treatment Plus Nicorandil | Walk Distance in Six Minute Walk (6-MWT) Test at Week 12 | 452.1 meters | Standard Deviation 116.87 |
| Standard Treatment | Walk Distance in Six Minute Walk (6-MWT) Test at Week 12 | 438.1 meters | Standard Deviation 107.42 |