SIGMART: Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01396395
• Collaborator: Merck Serono Co., Ltd., China (Industry)
• Enrollment: 402
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 12.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stable Angina; Coronary Disease	Drug: Nicorandil; Drug: Standard Treatment	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 402 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multi-center, Random, Open-label Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Standard treatment plus nicorandil The subjects will receive nicorandil 5 milligram (mg ) tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (such as aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors [(ACEIs] as permitted by disease condition /as per standard local practices/prescribed per discretion of investigators).	Drug: Nicorandil; The subjects will receive Nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with the standard treatment.; Drug: Standard 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.
Other: Standard treatment	Drug: Standard 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. Number of Arrhythmia Occurred Within 24 Hours [At Week 12]

   The number of ventricular tachycardia and premature ventricular beats that occurred within 24 hours.

8. 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.

9. Number of Subjects Experienced Angina Attack [Baseline up to 12 Weeks]

10. Frequency of Angina Attack [At Week 12]

    The total number of times angina attacks occurred within a week (number of times/week)

11. Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin [At Week 12]

12. Number of Nitroglycerin Tablets Consumed in a Week [At Week 12]

13. 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.

14. 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.

15. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For Locations in	Beijing		China

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany
• Merck Serono Co., Ltd., China

Investigators

• Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT01396395
• Other Study ID Numbers: EMR200101-501
• First Posted: Jul 18, 2011
• Last Update Posted: Apr 14, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Merck KGaA, Darmstadt, Germany: Nicorandil; Stable angina
• Additional relevant MeSH terms: Heart Diseases; Angina Pectoris; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Angina, Stable; Nicorandil

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	The subjects received nicorandil 5 milligram (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 the investigators.	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.
Period Title: Overall Study
STARTED	200	202
Safety Analysis Set	197	205
COMPLETED	160	175
NOT COMPLETED	40	27

Baseline Characteristics

Arm/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	200	202	402
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (10.16)	60.8 (9.94)	61.1 (10.04)
Sex: Female, Male (Count of Participants)
Female	58 29%	74 36.6%	132 32.8%
Male	142 71%	128 63.4%	270 67.2%

Outcome Measures

1. Primary Outcome

Title	Number of Myocardial Ischemia Attacks in 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	141	150
Mean (Standard Deviation) [ischemic attacks per 24 hours]	2.3 (8.46)	3.8 (18.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Treatment Plus Nicorandil, Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	poisson regression: Non-calibration mode
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.503
	Confidence Interval	(2-Sided) 95%; 0.435 to 0.581
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Treatment Plus Nicorandil, Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.0086
	Comments
	Method	Poisson regression: Calibration model
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.503
	Confidence Interval	(2-Sided) 95%; 0.301 to 0.840
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Total Myocardial Ischemic Burden at Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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 ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	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.
Measure Participants	133	146
Mean (Standard Deviation) [millimeter*minutes]	-38.63 (572.807)	29.26 (404.070)

3. Secondary Outcome

Title	Change From Baseline in Maximum ST-depression at Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	133	146
Mean (Standard Deviation) [millimeter]	0.25 (3.598)	0.36 (3.563)

4. Secondary Outcome

Title	Change From Baseline in Longest Duration of ST Segment Depression at Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	133	146
Mean (Standard Deviation) [seconds]	-3.8 (37.75)	3.4 (18.83)

5. Secondary Outcome

Title	Percentage of Subjects Experienced Ischemic Heart Attack During the Six-minute Walk Test
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	135	147
Number [percentage of subjects]	2.2	4.1

6. Secondary Outcome

Title	Heart Rate Variability (HRV) Rate: Time Domain
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	200	202
SDNN-24 hour (n=141, 149)	126.1 (35.58)	125.7 (33.25)
SDANN index (n=141, 149)	116.9 (37.44)	116.7 (33.65)
SDNN index (n=140, 147)	47.6 (14.60)	47.0 (14.99)

7. Secondary Outcome

Title	Heart Rate Variability (HRV) Rate: Frequency Domain Power-24 Hour
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	140	147
Mean (Standard Deviation) [millisecond square (ms^2)]	2397.0 (1527.37)	2328.6 (1458.31)

8. Secondary Outcome

Title	Number of Arrhythmia Occurred Within 24 Hours
Description	The number of ventricular tachycardia and premature ventricular beats that occurred within 24 hours.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	141	150
Ventricular tachycardia	0.8 (4.03)	5.2 (40.67)
Premature ventricular beat	134.8 (457.59)	569.1 (2538.17)

9. Secondary Outcome

Title	ECG QT Dispersion
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	74	69
Mean (Standard Deviation) [milliseconds]	0.1298 (0.17240)	0.1110 (0.15865)

10. Secondary Outcome

Title	Number of Subjects Experienced Angina Attack
Time Frame	Baseline up to 12 Weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	162	176
Number [subjects]	48	70

11. Secondary Outcome

Title	Frequency of Angina Attack
Description	The total number of times angina attacks occurred within a week (number of times/week)
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	45	70
Median (Inter-Quartile Range) [angina attacks per week]	1	2

12. Secondary Outcome

Title	Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	26	48
Number [subjects]	20	43

13. Secondary Outcome

Title	Number of Nitroglycerin Tablets Consumed in a Week
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	19	43
Median (Inter-Quartile Range) [tablets per week]	1	2

14. Secondary Outcome

Title	Walk Distance in Six Minute Walk (6-MWT) Test at Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	152	164
Mean (Standard Deviation) [meters]	452.1 (116.87)	438.1 (107.42)

15. Secondary Outcome

Title	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
Description	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 )

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil	Standard Treatment
Arm/Group Description	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).	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.
Measure Participants	197	205
TEAEs	23	13
SAEs	9	7
AEs Leading to Death	1	1
AEs Leading to Discontinuation	16	0

16. Secondary Outcome

Title	Number of Subjects Who Showed Compliance to Nicorandil
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Standard Treatment Plus Nicorandil
Arm/Group Description	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).
Measure Participants	191
Number [subjects]	181

Adverse Events

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 ).
Arm/Group Title	Standard Treatment Plus Nicorandil		Standard Treatment
Arm/Group Description	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).		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.
All Cause Mortality
	Standard Treatment Plus Nicorandil		Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Treatment Plus Nicorandil		Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/197 (4.6%)		7/205 (3.4%)
Cardiac disorders
Sudden death	1/197 (0.5%)		0/205 (0%)
Cardiac sudden death	0/197 (0%)		1/205 (0.5%)
Angina	1/197 (0.5%)		0/205 (0%)
Supraventricular tachycardia	1/197 (0.5%)		0/205 (0%)
Acute coronary syndrome	0/197 (0%)		1/205 (0.5%)
Unstable angina	1/197 (0.5%)		0/205 (0%)
Sick sinus syndrome	0/197 (0%)		1/205 (0.5%)
Coronary artery disease	1/197 (0.5%)		1/205 (0.5%)
Eye disorders
Glaucoma	1/197 (0.5%)		0/205 (0%)
Gastrointestinal disorders
Gastric ulcer	1/197 (0.5%)		0/205 (0%)
Gastroenteritis'	0/197 (0%)		1/205 (0.5%)
Duodenal ulcer	1/197 (0.5%)		0/205 (0%)
Investigations
Increased blood pressure	1/197 (0.5%)		0/205 (0%)
Metabolism and nutrition disorders
Peripheral edema	1/197 (0.5%)		0/205 (0%)
Diabetic foot	1/197 (0.5%)		0/205 (0%)
Diabetes	0/197 (0%)		1/205 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma	0/197 (0%)		1/205 (0.5%)
Multiple myeloma	1/197 (0.5%)		0/205 (0%)
Renal and urinary disorders
Chronic renal failure	1/197 (0.5%)		0/205 (0%)
Other (Not Including Serious) Adverse Events
	Standard Treatment Plus Nicorandil		Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/197 (6.1%)		1/205 (0.5%)
Cardiac disorders
Chest pain	2/197 (1%)		1/205 (0.5%)
Gastrointestinal disorders
Nausea	4/197 (2%)		0/205 (0%)
Nervous system disorders
Dizziness	2/197 (1%)		0/205 (0%)
Headache	6/197 (3%)		0/205 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.