Stable AnginaPhase 4SIGMARTNCT01396395
Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina
A Phase 4 study testing Nicorandil and Standard Treatment in people with Stable Angina and Coronary Disease, run by Merck KGaA, Darmstadt, Germany at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stable Angina, Coronary Disease
- What is being tested?
- Nicorandil and Standard Treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 402 participants
- Where
- 1 siteChina
- Study dates
- Sep 2011to May 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Multi-center, Random, Open-label Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina
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.
- Conditions
- Stable Angina, Coronary Disease
- Being tested
- Nicorandil, Standard Treatment
- Keywords
- Nicorandil, Stable angina
- Medical subject headings
- Angina, Stable, Coronary Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicorandilDrug
The subjects will receive Nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with the 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.
| Study group | Role | What they receive |
|---|---|---|
| Standard treatment plus nicorandil | Experimental | 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). Receives: Drug: Nicorandil; Drug: Standard Treatment |
| Standard treatment | Other | Not described Receives: Drug: Standard Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At Week 12
Secondary outcomes (15)
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: At Week 12
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.
Measured: At Week 12
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.
Measured: At Week 12
Number of Arrhythmia Occurred Within 24 Hours
The number of ventricular tachycardia and premature ventricular beats that occurred within 24 hours.
Measured: At Week 12
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.
Measured: At Week 12
Number of Subjects Experienced Angina Attack
Measured: Baseline up to 12 Weeks
Frequency of Angina Attack
The total number of times angina attacks occurred within a week (number of times/week)
Measured: At Week 12
Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin
Measured: At Week 12
Number of Nitroglycerin Tablets Consumed in a Week
Measured: At Week 12
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.
Measured: At Week 12
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.
Measured: From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks )
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.
Measured: Baseline up to 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2011 (estimated)
- Study startSep 2011
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stable AnginaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 402 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Serono Co., Ltd., China
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01396395
- Sponsor's protocol ID
- EMR200101-501
- Acronym
- SIGMART
- Status last verified
- Mar 2016
- First submitted
- 15 Jul 2011
- Last updated
- 14 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 27657471
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multi-center, Random, Open-label Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina
- ClinicalTrials.gov ID
- NCT01396395
- Acronym / sponsor ID
- SIGMART / EMR200101-501
- Conditions
- Stable Angina, Coronary Disease
- Keywords
- Nicorandil, Stable angina
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 402 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Serono Co., Ltd., China
- Study start
- Sep 2011
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 18 Jul 2011 (estimated)
- Results
- Posted 14 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard treatment plus nicorandil | Experimental | Drug: Nicorandil, Drug: Standard TreatmentThe 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). |
| Standard treatment | Other | Drug: Standard Treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subject must be diagnosed as stable CHD, and must have at least one of these histories:
- Subjects must have at least 2 times of typical symptoms of myocardial ischemia occurred within a week Other protocol defined inclusion criteria could apply
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NicorandilThe 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 plus nicorandil |
| Standard TreatmentThe 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. | Drug | Standard treatment, Standard treatment plus nicorandil |
Primary outcome
Number of Myocardial Ischemia Attacks in 24 Hours
Time frame: 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.
15 secondary outcomes
Change From Baseline in Total Myocardial Ischemic Burden at Week 12
Time frame: Baseline, Week 12
Change From Baseline in Maximum ST-depression at Week 12
Time frame: Baseline, Week 12
Change From Baseline in Longest Duration of ST Segment Depression at Week 12
Time frame: Baseline, Week 12
Percentage of Subjects Experienced Ischemic Heart Attack During the Six-minute Walk Test
Time frame: At Week 12
Heart Rate Variability (HRV) Rate: Time Domain
Time frame: At Week 12
Heart Rate Variability (HRV) Rate: Frequency Domain Power-24 Hour
Time frame: At Week 12
Number of Arrhythmia Occurred Within 24 Hours
Time frame: At Week 12
ECG QT Dispersion
Time frame: At Week 12
Number of Subjects Experienced Angina Attack
Time frame: Baseline up to 12 Weeks
Frequency of Angina Attack
Time frame: At Week 12
Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin
Time frame: At Week 12
Number of Nitroglycerin Tablets Consumed in a Week
Time frame: At Week 12
Walk Distance in Six Minute Walk (6-MWT) Test at Week 12
Time frame: At Week 12
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
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 )
Number of Subjects Who Showed Compliance to Nicorandil
Time frame: Baseline up to 12 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27657471Jiang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nicorandil and Standard Treatment in people with Stable Angina and Coronary Disease, run by Merck KGaA, Darmstadt, Germany at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Myocardial Ischemia Attacks in 24 Hours (time frame: At Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01396395, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2016.