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

This study has been completed.
Sponsor:
Collaborator:
Merck Serono Co., Ltd., China
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01396395
First received: July 15, 2011
Last updated: March 15, 2016
Last verified: March 2016
  Purpose
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 Intervention Phase
Stable Angina
Coronary Disease
Drug: Nicorandil
Drug: Standard Treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Myocardial Ischemia Attacks in 24 Hours [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    The number of ventricular tachycardia and premature ventricular beats that occurred within 24 hours.

  • ECG QT Dispersion [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline up to 12 Weeks ] [ Designated as safety issue: No ]
  • Frequency of Angina Attack [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
  • Number of Nitroglycerin Tablets Consumed in a Week [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
  • Walk Distance in Six Minute Walk (6-MWT) Test at Week 12 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    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 [ 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 ) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline up to 12 Weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 402
Study Start Date: September 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01396395

Locations
China
For Locations in
Beijing, China
Sponsors and Collaborators
Merck KGaA
Merck Serono Co., Ltd., China
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01396395     History of Changes
Other Study ID Numbers: EMR200101-501 
Study First Received: July 15, 2011
Results First Received: September 14, 2015
Last Updated: March 15, 2016
Health Authority: China: Ethics Committee

Keywords provided by Merck KGaA:
Nicorandil
Stable angina

Additional relevant MeSH terms:
Heart Diseases
Angina Pectoris
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Angina, Stable
Cardiovascular Diseases
Chest Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Vascular Diseases
Signs and Symptoms
Arteriosclerosis
Arterial Occlusive Diseases
Nicorandil
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 24, 2016