To Assess the Anti-anginal Safety and Efficacy of Ivabradine in Subjects With Stable，Symptomatic Chronic Angina
Study Details
Study Description
Brief Summary
Arms Assigned Interventions
Experimental: Ivabradine Ivabradine 5 mg twice a day for first 4 weeks and 7.5mg twice a day when positive ETT and HR>60times/min or negative ETT and HR>80times/min of subjects.
Active Comparator: Atenolol Atenolol 12.5 mg twice a day for first 4 weeks and 25mg twice a day when positive ETT and heard rate>60times/min or negative ETT and HR >80times/min of subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
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Washout period：Chronic angina patients stop using medicine that affect heart rate. The patients undergoes ETT after 2-7 days and positive ETT into the treatment period(If not take similar medicine, patients can be carried out ETT directly)。
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Treatment period：Patients carried out ETT after therapy with Ivabradine(5mg,bid)/ Atenolol(12.5mg,bid) for 4 weeks.The dose adjust base on test result and heart rate, Ivabradine(5mg,bid)/Atenolol(12.5mg,bid) or Ivabradine(7.5mg,bid)/ Atenolol(25mg,bid) for 8 weeks and carried out ETT.
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security period：After the treatment period, all patients to take Atenolol 12.5mg/ 25mg bid 1 week.
If heart rate are low 50 times/min after taking Ivabradine 5mg/ Atenolol 12.5mg, subjects should withdrawal and dropped out study. If subjects heart rate are low 50 times/min after taking Ivabradine 7.5mg/ Atenolol 25mg, subjects should change the dose to Ivabradine 5mg/ Atenolol 12.5mg.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ivabradine Ivabradine 5 mg twice a day for first 4 weeks and 7.5mg twice a day when positive ETT and HR（heard rate）>60times/min or negative ETT and HR（heard rate）>80times/min of subjects. |
Drug: Ivabradine
Not Provided
Other Names:
|
| Active Comparator: Atenolol Atenolol 12.5 mg twice a day for first 4 weeks and 25mg twice a day when positive ETT and HR（heard rate）>60times/min or negative ETT and HR （heard rate）>80times/min of subjects. |
Drug: Atenolol
Not Provided
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The primary efficacy endpoint is Change from total exercise duration in exercise tolerance test (ETT) [Baseline and end of treatment (Week 12) .]
Secondary Outcome Measures
- Time to angina in exercise tolerance test. [12 weeks]
- Time to 1 mm ST-segment depression in exercise tolerance test [12 weeks]
- Number of angina attacks in exercise tolerance test per week [12 weeks]
- Number of sublingual nitroglycerin consumption per week [12 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
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male or female aged 18 to 75 years
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Clearly understand the study and participate in it voluntarily; the informed consent should be signed in person or by legal guardian.
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Chronic Stable Angina was confirmed by clinic over 3 months.
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Patients with clinical diagnosis of chronic stable angina and must meet one of the following conditions:
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Patients who have a history of myocardial infarction over 3 months.
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Patients who have received coronary intervention or CABG（Coronary Artery Bypass Grafting） over 6 months.
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Stenosis of more than 50% in at least one major epicardial coronary artery shown by Coronary Angiograph.
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Ischemic electrocardiogram changes：ST-segment depression ≥ 1.0 mm compared with P-R or elevate≥1.0 mm during exercise ECG Computed Tomography Angiography (CTA) showed more than 50% stenosis with typical angina symptoms
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ultrasonic cardiogram disclosed that left ventricular ejection fraction ≥50 %.
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Patients who manifested positive ETT (exercise tolerance testing) (defined as ST-segment depression ≥ 1 mm compared with at rest, with or without limiting angina) at screening.
Exclusion Criteria:
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Clinically significant Valvular disease, congenital heart disease, pulmonary hypertension, cerebral apoplexy, dissecting aneurysm, hypertrophic cardiomyopathy, acute myocarditis/cp.
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Patients with myocardial infarction within the preceding 3 months
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Patients have received Coronary angioplasty or CABG within the preceding 6 months.
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Patients who have severity vessels disease with left main coronary artery but have no valid treatment.
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Patients with congestive heart failure(New York Heart Association class III or IV)or acute pulmonary edema.
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Patients whose rest heart rate< 60 bpm.
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Patients with nonrespiratory sinus arrhythmia or arrhythmia(e.g.,AVB(auriculo-ventricular block)ⅡⅢ,atrial fibrillation,atrial flutter,SSS(sick sinus syndrome)) or implantable cardiac defibrillator (ICD).
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Patient with any conditions that interfered the performance of exercise tolerance test or a history of an abnormal exercise response limited by electrocardiograph (ECG) changes.
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Patient with uncontrolled hypertension (seated systolic blood pressure (SBP）≥180 mmHg or diastolic blood pressure (DBP) ≥100 mmHg); SBP<90 mmHg and/or DBP<60 mmHg
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Diabetic with uncontrolled blood glucose(FBG≥11.1 mmol/L and/or RBG≥13.6 mmol/L）
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Patients with anemia(male:Hb≤120 g/L；female：Hb≤110 g/L)
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Patients complicated with systemic diseases included thyroid dysfunction、glaucoma、cataract，neurological、mental、psychological disease and any other disease that influence the judgment.
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Severe concurrent pathology, including terminal illness (cancer, AIDS, etc.).
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Patients with mental or legal disorder.
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Patients who were suspected addicted into alcohol or drug abuse or with severe complications that would make the condition more complicated assessed by the investigator.
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People have liver or renal dysfunction (ALT≥2×ULN、AST≥2×ULN、eGFR≤60ml/min/1.73m2）
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Patients who should use unapproved drug during the study.
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Patients who accepted amiodarone(in recent 3 months)and/or benzetimide、βblockers（in recent 7 days)、
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Patients with history of allergy or suspected allergic to the drug（e.g.，Hydrochloric ivabradine,atenolol, βblockers）or lactose.
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Woman who disagree with contraception during treatment period ，with pregnancy, lactation or positive result of pregnancy test.
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Patients with Chronic Obstructive Pulmonary Disease (COPD) requiring bronchodilators.
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Patients who is participating in other trials or has been participated in other trials in recent 3 months
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Patients who were unable to participate in the study as judged by investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Guizhou Provincial People's Hospital | Guiyang | Guizhou | China | 550001 |
| 2 | Zhongda Hospital Southeast University | Nanjing | Jiangsu | China | 210009 |
| 3 | The General Hospital of Shenyang Military | Shenyang | Liaoning | China | 110016 |
Sponsors and Collaborators
- Xintong Pharmacy Company
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- A130901CSPF01