To Assess the Anti-anginal Safety and Efficacy of Ivabradine in Subjects With Stable，Symptomatic Chronic Angina

Evaluation of the Anti-anginal Efficacy and Safety of Ivabradine Used in Patients With Stable Effort Angina Pectoris. A 12 Weeks Randomised, Double-blind Controlled, Parallel-group, Multicentre Study

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.

Study Overview

• Status: Unknown
• Conditions: Angina Pectoris
• Intervention / Treatment: Drug: Ivabradine; Drug: Atenolol

Detailed Description

1. 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)。
2. 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.
3. 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 Type: Interventional
• Enrollment (Anticipated): 336
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guizhou
    • Guiyang, Guizhou, China, 550001
      • Recruiting
      • Guizhou Provincial People's Hospital
      • Contact: Ping Zhang; Phone Number: 0851-5623033; Email: xin7110p@163.com
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Zhongda Hospital Southeast University
      • Contact: Genshan Ma; Phone Number: 025-83272038; Email: Magenshan@hotmail.com
  • Liaoning
    • Shenyang, Liaoning, China, 110016
      • Recruiting
      • The General Hospital of Shenyang Military
      • Contact: Yaling Han; Phone Number: 024-28897309; Email: hanyaling@263.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. male or female aged 18 to 75 years
2. Clearly understand the study and participate in it voluntarily; the informed consent should be signed in person or by legal guardian.
3. Chronic Stable Angina was confirmed by clinic over 3 months.

4. Patients with clinical diagnosis of chronic stable angina and must meet one of the following conditions:

   • Patients who have a history of myocardial infarction over 3 months.
   • Patients who have received coronary intervention or CABG（Coronary Artery Bypass Grafting） over 6 months.
   • Stenosis of more than 50% in at least one major epicardial coronary artery shown by Coronary Angiograph.
   • 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
5. ultrasonic cardiogram disclosed that left ventricular ejection fraction ≥50 %.
6. 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:

1. Clinically significant Valvular disease, congenital heart disease, pulmonary hypertension, cerebral apoplexy, dissecting aneurysm, hypertrophic cardiomyopathy, acute myocarditis/cp.
2. Patients with myocardial infarction within the preceding 3 months
3. Patients have received Coronary angioplasty or CABG within the preceding 6 months.
4. Patients who have severity vessels disease with left main coronary artery but have no valid treatment.
5. Patients with congestive heart failure(New York Heart Association class III or IV)or acute pulmonary edema.
6. Patients whose rest heart rate< 60 bpm.
7. 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).
8. 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.
9. 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
10. Diabetic with uncontrolled blood glucose(FBG≥11.1 mmol/L and/or RBG≥13.6 mmol/L）
11. Patients with anemia(male:Hb≤120 g/L；female：Hb≤110 g/L)
12. Patients complicated with systemic diseases included thyroid dysfunction、glaucoma、cataract，neurological、mental、psychological disease and any other disease that influence the judgment.
13. Severe concurrent pathology, including terminal illness (cancer, AIDS, etc.).
14. Patients with mental or legal disorder.
15. 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.
16. People have liver or renal dysfunction (ALT≥2×ULN、AST≥2×ULN、eGFR≤60ml/min/1.73m2）
17. Patients who should use unapproved drug during the study.
18. Patients who accepted amiodarone(in recent 3 months)and/or benzetimide、βblockers（in recent 7 days)、
19. Patients with history of allergy or suspected allergic to the drug（e.g.，Hydrochloric ivabradine,atenolol, βblockers）or lactose.
20. Woman who disagree with contraception during treatment period ，with pregnancy, lactation or positive result of pregnancy test.
21. Patients with Chronic Obstructive Pulmonary Disease (COPD) requiring bronchodilators.
22. Patients who is participating in other trials or has been participated in other trials in recent 3 months
23. Patients who were unable to participate in the study as judged by investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Not Provided
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: Not Provided

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Xintong Pharmacy Company

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: November 29, 2015
• First Submitted That Met QC Criteria: December 4, 2015
• First Posted (Estimate): December 7, 2015

Study Record Updates

• Last Update Posted (Estimate): December 7, 2015
• Last Update Submitted That Met QC Criteria: December 4, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Atenolol
• Other Study ID Numbers: A130901CSPF01