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

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

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.

Study Overview

• Status: Completed
• Conditions: Angina Pectoris
• Intervention / Treatment: Drug: Succinate Metoprolol (Betaloc ZOK®); Drug: Succinate Metoprolol (Betaloc ZOK®)

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Tianjing, China
    • Research Site
  • Beijing
    • Beijing, Beijing, China
      • Research Site
  • Guangdong
    • Guangzhou, Guangdong, China
      • Research Site
  • Hebei
    • Tangshan, Hebei, China
      • Research Site
  • Henan
    • Zhengzhou, Henan, China
      • Research Site
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Research Site
  • Liaoning
    • Jingzhou, Liaoning, China
      • Research Site
    • Shenyang, Liaoning, China
      • Research Site
  • Shanghai
    • Shanghai, Shanghai, China
      • Research Site
  • Shanxi
    • Taiyuan, Shanxi, China
      • Research Site

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:

• 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2	Drug: Succinate Metoprolol (Betaloc ZOK®); 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; Drug: Succinate Metoprolol (Betaloc ZOK®); 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
Active Comparator: 1	Drug: Succinate Metoprolol (Betaloc ZOK®); 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; Drug: Succinate Metoprolol (Betaloc ZOK®); 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Huo Yong, Department of Cardiology, Peking University First Hospital; Study Director: Helen Lin, AstraZeneca China

Publications and helpful links

Helpful Links

• Related Info
• CSR-D4022L00008.pdf

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: September 30, 2010
• First Posted (Estimate): October 1, 2010

Study Record Updates

• Last Update Posted (Estimate): September 5, 2014
• Last Update Submitted That Met QC Criteria: August 26, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: chest pain; angina pectoris; heart rate
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Stable; 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; Metoprolol
• Other Study ID Numbers: D4022L00008