Efficacy and Safety of Wen Xin Granules for the Treatment of Unstable Angina Pectoris

Study Overview
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Brief Summary
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This is a double-blind, randomized placebo-controlled trial which aims to evaluate the efficacy and safety of Wen Xin granule in patients with unstable angina pectoris.

Detailed Description
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Coronary heart disease has remained the leading cause of death worldwide over the past decades. Unstable angina is a clinical syndrome intermediate in severity between stable angina and acute myocardial infarction with high morbidity and mortality. Standard drug therapy and invasive revascularization are effective in decreasing progression to infarction, reducing symptoms and multiple hospitalizations, in most cases without a decrease in the long-term mortality rate. However, there are still many patients with persistence or recurrence of angina despite standard medical therapy and/or revascularization. Wen Xin granule, as a Chinese herbal medicine has shown great effect in patients with unstable angina in our clinical. However, there is still insufficient evidence on his specific efficacy and safety. Therefor, we'd like to evaluate the efficacy and safety of Wen Xin granule in patients with unstable angina through this multi-center, double-blind, randomized placebo-controlled trial.

Official Title
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Efficacy and Safety of Chinese Herbal Medicine Wen Xin Granules for the Treatment of Unstable Angina Pectoris With Yang Deficiency and Blood Stasis Syndrome: Study Protocol for a Randomized Controlled Trial

Conditions
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Coronary Heart Disease, Unstable Angina, Chinese Herbal Medicine

Intervention / Treatment
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* Drug: Wen Xin granule
* Drug: Clopidogrel Hydrogen Sulfate 75 MG Oral Tablet
* Drug: Atorvastatin Calcium
* Drug: Isosorbide Mononitrate Tab 20 MG
* Drug: Metoprolol Tartrate Tab 25 MG
* Drug: Aspirin Enteric-coated Tablets
* Drug: WXG placebo
* Drug: Trimetazidine Dihydrochloride Tablets
* Drug: glyceryl trinitrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged between 35 and 75 years of age; diagnosed with CAD through coronary arteriography, clinically diagnosed with UAP in low or medium risk; belong to Yang deficiency and blood stasis syndrome according to TCM, and give written informed consent. For the diagnostic criteria of UAP, the investigators will refer to 2014 AHA/ACC Guidelines for the Diagnosis and Management of Non-ST-Elevation Acute Coronary Syndromes. For the TCM diagnostic criteria, the investigators will refer to Guidelines for Clinical Research into New Traditional Chinese Medicine Drugs for Chest Obstruction (2002 edition). Exclusion Criteria: chest pain caused by congenital heart diseases, valvular heart disease, severe neurosis, or arrhythmia with New York Heart Association class III or IV heart failure, in acute phase of cerebral infarction; with uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >95 mmHg in the resting state) with uncontrolled hyperglycemia or diabetic complications, with mental and neurological abnormalities or dysgnosia; female patients in pregnancy or lactation; by participating in other clinical trials.

Ages Eligible for Study
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Minimum Age: 35 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
Interventional Model Description: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Wen Xin granule<br>Patients are given Wen Xin granule by mouth, one dose daily for 2 months & Conventional western medicine, including Aspirin Enteric-coated Tablets 100mg qd, Clopidogrel Hydrogen Sulfate 75 mg qd, Atorvastatin Calcium 20mg qn, Isosorbide Mononitrate Tab 20 mg bid, Metoprolol Tartrate Tab 25mg, Trimetazidine Dihydrochloride Tablets 20mg tid. | Drug: Wen Xin granule<br>* one dose daily, two times per day.<br>* Other names: WXG;Drug: Clopidogrel Hydrogen Sulfate 75 MG Oral Tablet<br>* one tablet daily. (for patients who can't use aspirin)<br>Drug: Atorvastatin Calcium<br>* 20 mg tablet, one tablet each night.<br>Drug: Isosorbide Mononitrate Tab 20 MG<br>* one tablet， twice daily.<br>Drug: Metoprolol Tartrate Tab 25 MG<br>* 12.5 mg or 25 mg, two times daily.<br>Drug: Aspirin Enteric-coated Tablets<br>* 100mg tablet, one tablet daily.<br>Drug: Trimetazidine Dihydrochloride Tablets<br>* 20 mg tablet, one tablet three times daily.<br>Drug: glyceryl trinitrate<br>* be taken when angina pectoris attacks.<br>|
| Placebo Comparator: WXG placebo<br>Patients are given Wen Xin granule placebo by mouth, one dose daily for 2 months & Conventional western medicine, including Aspirin Enteric-coated Tablets 100mg qd, Clopidogrel Hydrogen Sulfate 75 mg qd, Atorvastatin Calcium 20mg qn, Isosorbide Mononitrate Tab 20 mg bid, Metoprolol Tartrate Tab 25mg, Trimetazidine Dihydrochloride Tablets 20mg tid. | Drug: Clopidogrel Hydrogen Sulfate 75 MG Oral Tablet<br>* one tablet daily. (for patients who can't use aspirin)<br>Drug: Atorvastatin Calcium<br>* 20 mg tablet, one tablet each night.<br>Drug: Isosorbide Mononitrate Tab 20 MG<br>* one tablet， twice daily.<br>Drug: Metoprolol Tartrate Tab 25 MG<br>* 12.5 mg or 25 mg, two times daily.<br>Drug: Aspirin Enteric-coated Tablets<br>* 100mg tablet, one tablet daily.<br>Drug: WXG placebo<br>* one dose daily, two times per day.<br>Drug: Trimetazidine Dihydrochloride Tablets<br>* 20 mg tablet, one tablet three times daily.<br>Drug: glyceryl trinitrate<br>* be taken when angina pectoris attacks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiovascular events | Including recurrent angina, acute myocardial infarction, severe arrhythmia, heart failure, and cardiac death. | Record the incidence of major adverse cardiovascular events in one year by follow-up. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The thrombelastograph | Parameters assessed by were R (represent clotting time), K and Angle (reflect clot strength and development), MA (maximum platelet-fibrin clot strength), CI (represents overall coagulability), and LY30 (represents lysis). | Before treatment and at eight weeks after treatment. | 
| TCM symptom scale score | TCM syndrome scale includes items of chest tightness, chest pain, heavy body, obesity, phlegm, dark complexion, tongue condition and pulse condition. The chest tightness and chest pain, have 4-grade options of none, mild, moderate and severe, marked as 0, 2, 4 and 6 respectively. The other items have two options of yes or no, marked as 0 and 1 respectively. The higher scores mean more serious symptoms. | Before treatment, four and eight weeks after treatment. | 
| Seattle angina questionnaire | The SAQ regroups 19 items measuring five specific scales: physical limitations, anginal stability, anginal frequency, treatment satisfaction and disease perception targeting a specific disease and treatment group. Higher scores mean a better outcome. | Before treatment, four and eight weeks after treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary heart disease, unstable angina, Chinese herbal medicine, Wen Xin granule, traditional Chinese medicine