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

Primary Purpose

Stable Angina, Coronary Disease

Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Nicorandil
Standard Treatment
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stable Angina focused on measuring Nicorandil, Stable angina

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • For Locations in

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Standard treatment plus nicorandil

Standard treatment

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
Number of Arrhythmia Occurred Within 24 Hours
The number of ventricular tachycardia and premature ventricular beats that occurred within 24 hours.
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.
Number of Subjects Experienced Angina Attack
Frequency of Angina Attack
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
Number of Nitroglycerin Tablets Consumed in a Week
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.
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.
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.

Full Information

First Posted
July 15, 2011
Last Updated
March 15, 2016
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., China
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1. Study Identification

Unique Protocol Identification Number
NCT01396395
Brief Title
Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina
Acronym
SIGMART
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 Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., China

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stable Angina, Coronary Disease
Keywords
Nicorandil, Stable angina

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
402 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard treatment plus nicorandil
Arm Type
Experimental
Arm Description
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).
Arm Title
Standard treatment
Arm Type
Other
Intervention Type
Drug
Intervention Name(s)
Nicorandil
Intervention Description
The subjects will receive Nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with the standard treatment.
Intervention Type
Drug
Intervention Name(s)
Standard Treatment
Intervention Description
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.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
Title
Number of Subjects Experienced Angina Attack
Time Frame
Baseline up to 12 Weeks
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
Title
Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin
Time Frame
At Week 12
Title
Number of Nitroglycerin Tablets Consumed in a Week
Time Frame
At Week 12
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
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 )
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject must be diagnosed as stable CHD, and must have at least one of these histories: A history of coronary revascularization Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Surgery at least 3 months ago Myocardial infarction More than 50 percent (%) stenosis detected by angiography 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
For Locations in
City
Beijing
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
27657471
Citation
Jiang J, Li Y, Zhou Y, Li X, Li H, Tang B, Dai X, Ma T, Li L, Huo Y. Oral nicorandil reduces ischemic attacks in patients with stable angina: A prospective, multicenter, open-label, randomized, controlled study. Int J Cardiol. 2016 Dec 1;224:183-187. doi: 10.1016/j.ijcard.2016.08.305. Epub 2016 Aug 21.
Results Reference
derived

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

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