Evaluation of Succinate Metoprolol on Heart Rate in the Stable Angina Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of Succinate Metoprolol(Betaloc ZOK®) (95 - 190 mg) on heart rate in the Stable angina patients.

Official Title
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A Randomised, Open Label, Parallel Group, Multicentre, Phase IV Study on the Effect of 8 Weeks Succinate Metoprolol (Betaloc ZOK®) (95 - 190 mg) on Heart Rate in the Stable Angina Patients

Conditions
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Angina Pectoris

Intervention / Treatment
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* Drug: Succinate Metoprolol (Betaloc ZOK®)
* Drug: Succinate Metoprolol (Betaloc ZOK®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Chinese patients Heart rate ≥ 65bpm Has been diagnosed as Stable angina for at least 1 month and with stable angina pectoris symptoms within 2 weeks previous to enrolment(Please find the diagnose criteria of Stable angina on Appendix C) With Left ventricular ejection fraction ≥ 50% according to ultrasound cardiogram; Has been on beta-blockers for at least 4 weeks*, on the dose equivalent to Betaloc ZOK® 23.75-47.5mg/day. Exclusion Criteria: Acute myocardial infarction within 6 months Unstable angina or Prinzmetal's angina II degree of AV block or greater Significant clinical, laboratory or electrocardiographic abnormalities that would place the subject at undue risk (in the Investigator's opinion) including: Significant renal impairment (serum creatinine > 2.0 mg/dL) Serum Alanine Aminotransferase or Aspartate Aminotransferase > 3 x upper limit of reference range Serum potassium < 3.0 mEq/L Serum sodium ≤ 130 mEq/L Acute or chronic hepatitis or cirrhosis (clinical diagnosis) Uncontrolled hyperthyroidism (clinical diagnosis) Systolic blood pressure ≥ 180 mmHg, or < 100mmHg at enrolment Patients with unstable, not compensated heart failure (pulmonary oedema, hypoperfusion or hypotension)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Succinate Metoprolol (Betaloc ZOK®)<br>* treatment with 47.5mg for two weeks, if tolerated and without Systolic blood pressure<100mmHg and heart rate <45 bpm according to 12-lead Electrocardiogram at Week 3, the dosage will be titrated to 95mg and last for another 6 weeks<br>|
| Experimental: 2<br> | Drug: Succinate Metoprolol (Betaloc ZOK®)<br>* Treatment with 95mg for two weeks, and if tolerated and without bradycardia symptoms presented, Systolic blood pressure<100mmHg and heart rate <45 bpm according to 12-lead Electrocardiogram at Week 3，the dosage will be force titrated to 190mg and last for another 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Impact on 24-hr Average Heart Rate Between Two Groups (Betaloc ZOK® 95mg vs. 190mg) | Difference of the 24-hr average heart rate between two groups after 8 weeks treatment. | After 8 weeks treatment in the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Impact on 24-hr Average Heart Rate From Baseline Within Groups | Difference of the 24-hr average heart rate within groups from baseline after 8 weeks treatment. | After 8 weeks treatment in the study | 
| The Different Impact on 24-hr Average Heart Rate Between Two Groups | Difference of the 24-hr average heart rate between two groups after 2 weeks of treatment. | After 2 weeks treatment in the study | 
| The Different Impact on 24-hr Average Heart Rate From Baseline Within Groups | Difference of the 24-hr average heart rate within groups from baseline after 2 weeks treatment. | After 2 weeks treatment in the study | 
| The Proportion of Patients With Resting Heart Rate Controlled to ≤60bpm Between Groups | Difference in proportions of patients who had resting heart rate controlled to ≤60 bpm after 2 weeks treatment between groups | After 2 weeks treatment | 
| The Proportion of Patients With Resting Heart Rate Controlled to ≤60bpm Between Groups | Difference in proportions of patients who had resting heart rate controlled to ≤60 bpm after 8 weeks treatment between groups | After 8 weeks treatment | 
| The Difference of Change From Baseline in Total Ischemic Burden Between Groups | Difference in change from baseline in TIB between two groups after 2 weeks treatment. Total Ischemic Burden (TIB) was defined as the sum of product of each ischemia episode lasting time and maximal ST elevation: TIB=Σ(STmax×Tisc). | After 2 weeks treatment | 
| The Difference of Change From Baseline in Total Ischemic Burden Between Groups | Difference in change from baseline in TIB between two groups after 8 weeks treatment. Total Ischemic Burden (TIB) was defined as the sum of product of each ischemia episode lasting time and maximal ST elevation: TIB=Σ(STmax×Tisc). | After 8 weeks treatment | 
| The Difference of Change From Baseline in Angina Frequency Between Groups | Difference in change from baseline of angina pectoris frequency between two groups after 2 weeks treatment. | After 2 weeks treatment | 
| The Difference of Change From Baseline in Angina Frequency Between Groups | Difference in change from baseline of angina pectoris frequency between two groups after 8 weeks treatment. | After 8 weeks treatment | 
| The Change From Baseline in Total Cholesterol | Difference of change from baseline in TC after 8 weeks treatment between groups. | After 8 weeks treatment | 
| The Change From Baseline in Fasting Plasma Glucose | Difference of change from baseline in FPG after 8 weeks treatment between groups. | After 8 weeks treatment | 
| The Change From Baseline in Triglycerides | Difference of change from baseline in TG after 8 weeks treatment between groups. | After 8 weeks treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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angina pectoris, chest pain, heart rate