Angina Pectoris
Conditions
Keywords
angina pectoris, chest pain, heart rate
Brief summary
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.
Interventions
DRUGSuccinate 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
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Impact on 24-hr Average Heart Rate Between Two Groups (Betaloc ZOK® 95mg vs. 190mg) | After 8 weeks treatment in the study | Difference of the 24-hr average heart rate between two groups after 8 weeks treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Different Impact on 24-hr Average Heart Rate Between Two Groups | After 2 weeks treatment in the study | Difference of the 24-hr average heart rate between two groups after 2 weeks of treatment. |
| The Different Impact on 24-hr Average Heart Rate From Baseline Within Groups | After 2 weeks treatment in the study | Difference of the 24-hr average heart rate within groups from baseline after 2 weeks treatment. |
| The Proportion of Patients With Resting Heart Rate Controlled to ≤60bpm Between Groups | After 2 weeks treatment | Difference in proportions of patients who had resting heart rate controlled to ≤60 bpm after 2 weeks treatment between groups |
| The Difference of Change From Baseline in Total Ischemic Burden Between Groups | After 2 weeks treatment | 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). |
| The Impact on 24-hr Average Heart Rate From Baseline Within Groups | After 8 weeks treatment in the study | Difference of the 24-hr average heart rate within groups from baseline after 8 weeks treatment. |
| The Change From Baseline in Total Cholesterol | After 8 weeks treatment | Difference of change from baseline in TC after 8 weeks treatment between groups. |
| The Change From Baseline in Fasting Plasma Glucose | After 8 weeks treatment | Difference of change from baseline in FPG after 8 weeks treatment between groups. |
| The Change From Baseline in Triglycerides | After 8 weeks treatment | Difference of change from baseline in TG after 8 weeks treatment between groups. |
| The Difference of Change From Baseline in Angina Frequency Between Groups | After 2 weeks treatment | Difference in change from baseline of angina pectoris frequency between two groups after 2 weeks treatment. |
Countries
China
Participant flow
Recruitment details
Safety Population is divided according to the actual dosage received by the patient, not the randomization. The patient will be high-dose group if the highest dose ever used is above 95mg; otherwise (if the highest dose ever used is equal to or lower than 95 mg) he/she will be low-dose group.
Pre-assignment details
Safety population- patients who received at least 1 dose of investigational product. During initial 1 week run-in period subjects were treated with 47.5mg Betaloc ZOK®. Patients started to take investigational product before randomization therefore, number of subjects in Safety population (274) is greater than number of randomized and treated (251)
Participants by arm
| Arm | Count |
|---|---|
| Active Comparator lead Electrocardiogram at Week 3, the dosage will be titrated to 95mg and last for another 6 weeks | 116 |
| Experimental lead Electrocardiogram at Week 3，the dosage will be force titrated to 190mg and last for another 6 weeks | 115 |
| Total | 231 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 8 |
| Overall Study | Incorrect Enrollment | 1 | 3 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Active Comparator | Experimental | Total |
|---|---|---|---|
| Age, Continuous | 59.3 Year STANDARD_DEVIATION 7.81 | 59.2 Year STANDARD_DEVIATION 9.25 | 59.2 Year STANDARD_DEVIATION 8.53 |
| Sex: Female, Male Female | 74 Participants | 81 Participants | 155 Participants |
| Sex: Female, Male Male | 42 Participants | 34 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 139 | 0 / 112 |
| serious Total, serious adverse events | 1 / 139 | 3 / 112 |
Outcome results
Primary
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.
Time frame: After 8 weeks treatment in the study
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Active Comparator | The Impact on 24-hr Average Heart Rate Between Two Groups (Betaloc ZOK® 95mg vs. 190mg) | Baseline | 71.4 Bpm | Standard Deviation 8.02 |
| Arm 1 - Active Comparator | The Impact on 24-hr Average Heart Rate Between Two Groups (Betaloc ZOK® 95mg vs. 190mg) | Week 9 | 70.9 Bpm | Standard Deviation 8.71 |
| Arm 2 - Experimental | The Impact on 24-hr Average Heart Rate Between Two Groups (Betaloc ZOK® 95mg vs. 190mg) | Baseline | 70.9 Bpm | Standard Deviation 8.19 |
| Arm 2 - Experimental | The Impact on 24-hr Average Heart Rate Between Two Groups (Betaloc ZOK® 95mg vs. 190mg) | Week 9 | 68.6 Bpm | Standard Deviation 8.4 |
Secondary
The Change From Baseline in Fasting Plasma Glucose
Difference of change from baseline in FPG after 8 weeks treatment between groups.
Time frame: After 8 weeks treatment
Population: All subjects who received at least one dose of randomized investigational product was included in the safety population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Active Comparator | The Change From Baseline in Fasting Plasma Glucose | 0.3844 mmol/L | 95% Confidence Interval 1.713 |
| Arm 2 - Experimental | The Change From Baseline in Fasting Plasma Glucose | 0.2487 mmol/L | 95% Confidence Interval 0.8809 |
Secondary
The Change From Baseline in Total Cholesterol
Difference of change from baseline in TC after 8 weeks treatment between groups.
Time frame: After 8 weeks treatment
Population: All subjects who received at least one dose of randomized investigational product was included in the safety population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Active Comparator | The Change From Baseline in Total Cholesterol | -0.0505 mmol/L | 95% Confidence Interval 0.8949 |
| Arm 2 - Experimental | The Change From Baseline in Total Cholesterol | 0.5825 mmol/L | 95% Confidence Interval 4.6175 |
Secondary
The Change From Baseline in Triglycerides
Difference of change from baseline in TG after 8 weeks treatment between groups.
Time frame: After 8 weeks treatment
Population: All subjects who received at least one dose of randomized investigational product was included in the safety population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Active Comparator | The Change From Baseline in Triglycerides | 0.1295 mmol/L | 95% Confidence Interval 0.7607 |
| Arm 2 - Experimental | The Change From Baseline in Triglycerides | 0.0937 mmol/L | 95% Confidence Interval 1.152 |
Secondary
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.
Time frame: After 2 weeks treatment
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm 1 - Active Comparator | The Difference of Change From Baseline in Angina Frequency Between Groups | -0.044 Attacks per week |
| Arm 2 - Experimental | The Difference of Change From Baseline in Angina Frequency Between Groups | -0.3243 Attacks per week |
Secondary
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.
Time frame: After 8 weeks treatment
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm 1 - Active Comparator | The Difference of Change From Baseline in Angina Frequency Between Groups | -0.3930 Attacks per week |
| Arm 2 - Experimental | The Difference of Change From Baseline in Angina Frequency Between Groups | -0.4453 Attacks per week |
Secondary
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).
Time frame: After 2 weeks treatment
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Active Comparator | The Difference of Change From Baseline in Total Ischemic Burden Between Groups | -5.3353 mm*min | 95% Confidence Interval 69.0874 |
| Arm 2 - Experimental | The Difference of Change From Baseline in Total Ischemic Burden Between Groups | -12.9874 mm*min | 95% Confidence Interval 66.3041 |
Secondary
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).
Time frame: After 8 weeks treatment
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Active Comparator | The Difference of Change From Baseline in Total Ischemic Burden Between Groups | 22.2905 mm*min | 95% Confidence Interval 112.1215 |
| Arm 2 - Experimental | The Difference of Change From Baseline in Total Ischemic Burden Between Groups | -7.6586 mm*min | 95% Confidence Interval 79.1887 |
Secondary
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.
Time frame: After 2 weeks treatment in the study
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Active Comparator | The Different Impact on 24-hr Average Heart Rate Between Two Groups | 70.6 Bpm | Standard Deviation 7.75 |
| Arm 2 - Experimental | The Different Impact on 24-hr Average Heart Rate Between Two Groups | 69.2 Bpm | Standard Deviation 7.82 |
Secondary
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.
Time frame: After 2 weeks treatment in the study
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Active Comparator | The Different Impact on 24-hr Average Heart Rate From Baseline Within Groups | -0.4938 Bpm | 95% Confidence Interval 4.69 |
| Arm 2 - Experimental | The Different Impact on 24-hr Average Heart Rate From Baseline Within Groups | -2.1383 Bpm | 95% Confidence Interval 5.71 |
Secondary
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.
Time frame: After 8 weeks treatment in the study
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Active Comparator | The Impact on 24-hr Average Heart Rate From Baseline Within Groups | -0.6244 Bpm | 95% Confidence Interval 7.16 |
| Arm 2 - Experimental | The Impact on 24-hr Average Heart Rate From Baseline Within Groups | -2.9858 Bpm | 95% Confidence Interval 6.62 |
Secondary
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
Time frame: After 8 weeks treatment
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 - Active Comparator | The Proportion of Patients With Resting Heart Rate Controlled to ≤60bpm Between Groups | 28 Participants |
| Arm 2 - Experimental | The Proportion of Patients With Resting Heart Rate Controlled to ≤60bpm Between Groups | 46 Participants |
Secondary
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
Time frame: After 2 weeks treatment
Population: ITT population was defined as all randomized subjects who had taken at least one dose of trial treatment, who had measurements at baseline for one or more efficacy variables and at least one post baseline measurement for the same variables in the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 - Active Comparator | The Proportion of Patients With Resting Heart Rate Controlled to ≤60bpm Between Groups | 25 Participants |
| Arm 2 - Experimental | The Proportion of Patients With Resting Heart Rate Controlled to ≤60bpm Between Groups | 28 Participants |