Danhong Injection in the Treatment of Chronic Stable Angina

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effect of Danhong Injection on the relief of angina with the use of the Seattle Angina Questionnaire among patients with stable angina patients

Official Title
-----------------
A Randomized, Multi-center, Double-blind, Placebo-controlled Trial of Danhong Injection in the Treatment of Chronic Stable Angina

Conditions
-----------------
Chronic Stable Angina

Intervention / Treatment
-----------------
* Drug: Danhong injection
* Other: Standard medical care
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female or male inpatients. Age: 18 - 70 years. Patients with clinical diagnosis of chronic stable angina and must meet one of the following conditions:1）Patients who have a history of myocardial infarction and ST-T changes;2）Stenosis of more than 50% in at least one major epicardial coronary artery shown by Coronary Angiograph or CT Angiography; 3）Patients with coronary heart disease were determined by radionuclide angiocardiography. Clinical diagnosis of Xueyu Zheng (Blood Stasis Syndrome) as the scores of Chinese medicine symptoms scales of Xueyu Zheng in angina ≥ 15. The Chinese medicine symptoms scales of Xueyu Zheng is defined as following (1)chest pain-10, (2)chest distress-10, (3) palpitation-5, (4)purple or dark lip-5, (5) purple or dark tongue-5, (6) unsmooth pulse-5. Patients with moderate angina pectoris (The definition of moderate angina pectoris  is in accordance with the Canadian Cardiovascular Society (CCS) grading of angina pectoris,which be classified to II or III. Patient is willing to participate voluntarily and to sign a written patient informed consent. Exclusion Criteria: Woman with pregnancy, lactation or positive result of pregnancy test, or woman who is under menstrual period. Woman who disagree with contraception during treatment period Patients with severe complications that would make the condition more complicated assessed by the investigator, including liver or renal dysfunction, severe cardiopulmonary dysfunction, pulmonary hypertension, chronic obstructive pulmonary disease, a history of epilepsy or cerebral hemorrhage . Patients who were angina-free during the run-in period without taking any drug. Patients with myocardial infarction or Canadian Cardiovascular Society (CCS) grading of angina pectoris class IV within the preceding 3 months Patients with chest pain caused by other disease (e.g., acute myocardial infarction，severe neurosis，menopausal syndrome，hyperthyroidism). Patients with history of drug-induced bleeding or history of bleeding caused by warfarin. Patients with history of hematopoietic system diseases. Patients who had surgery within the past 4 weeks and have hemorrhagic tendency. Patients who is participating in other trials or has been participated in other trials in recent 3 months. Patients with history of allergy or suspected allergic to the drug. Patients who were suspected addicted into alcohol or drug abuse in the past 2 years. Patients with mental disorder. Patients who were unable to participate in the study as judged by investigator. Patients who were family members or relatives of the research center staffs.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Danhong injection<br>Based on the standard medical care, 40ml of Danhong injection, added into 250ml of 0.9% saline, given by continuous IV infusion at 2.5ml/min within 2 hours. | Drug: Danhong injection<br>* A kind of injection made from two kind of Chinese herbs: salvia miltiorrhiza and safflower<br>Other: Standard medical care<br>* Standard medical care is in accordance with China Guideline for the diagnosis and treatment of Chronic Stable Angina (2007).<br>|
| Placebo Comparator: Placebo<br>Based on the standard medical care, placebo was 40ml of 0.9% saline, added into 250ml of 0.9% saline, given by continuous IV infusion at 2.5ml/min within 2 hours. | Other: Standard medical care<br>* Standard medical care is in accordance with China Guideline for the diagnosis and treatment of Chronic Stable Angina (2007).<br>Drug: Placebo<br>* 0.9% saline added into 250ml 0.9% saline by an independent research nurse, sealed with brown bag in order to make the investigators and patients blinded, using brown infusion tube for infusion.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients in each treatment group who had clinically significant change as defined by the angina-frequency score on the Seattle Angina Questionnaire at day 30 | Seattle Angina Questionnaire, a 19-item questionnaire that quantifies physical limitations due to angina, any recent change in the severity of angina, the frequency of angina, satisfaction with treatment, and quality of life. Scores range from 0 to 100; higher scores indicate better health status.With a score of 20 or more on the angina-frequency scale indicating that the patient was clinically significant change. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total score of symptoms questionnaire of TCM | The symptoms questionnaire of TCM consists of 6 symptoms that described in traditional Chinese medicine, including chest pain, chest distress, palpitation, dark-purple lip, dark-purple tongue and unsmooth pulse. Each symptom was assessed by the Visual Analogue Scale（VAS），where a higher score meant higher severity. | Day 0, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| The proportion of patients in each treatment group who had clinically significant changes in the other four Seattle Angina Questionnaire scales （The physical limitation, angina stability, treatment satisfaction, and quality of life） | We defined clinical significant changes as a difference of 8 points or more on the physical-limitation scale, 25 or more on the angina-stability scale, 12 or more on the treatment-satisfaction scale, or 16 or more on the quality-of-life scale. | Day 0, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| The frequency of anginal attack every week | The frequency of anginal attack was recorded by the patients with the use of the diary cards which will be collected from the run-in period (Day -7) to the end of follow-up (Day 90). | Day-7 (if exist), Day 0, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Canadian Cardiovascular Society (CCS) grading of angina pectoris |  | Day 0, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Consumption of Short-acting Nitrates |  | Day -7( if exist), Day 0, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Change in the electrocardiogram (EKG) |  | Day 0, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Changes in the Serum Lipid, the high-sensitivity C-Reactive Protein(hs-CRP) and the Platelet Aggregation Rate |  | Day 0, Day 14 | 
| Incidence of new-onset major vascular events in 90 days | Major adverse vascular events include ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction and vascular-related death. | Day 90 | 
| Overall mortality in 90 days |  | Day 90 | 
| Incidence of severe hemorrhages in 90 days | The definition of Severe hemorrhages is in accordance with the GUSTO bleeding criteria, including fatal intracranial hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH) or which could result in substantial hemodynamic compromise requiring treatment. | Day 90 | 
| Incidence of moderate hemorrhages in 90 days | The definition of moderate hemorrhages is in accordance with the GUSTO bleeding criteria, which requires blood transfusion but not results in hemodynamic compromise. | Day 90 | 
| Documentation of adverse events (AEs) and serious AEs |  | 90 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Stable Angina, Randomized Controlled Trial, Traditional Chinese Medicine