Clinical Evaluation of Compound Salvia Droplet Pills in the Treatment of Stable Angina Pectoris:Study Protocol for a Randomized Double-blind Control Trial


 Background 
SAP (Stable Angina Pectoris, SAP) is a clinical syndrome characterized by acute and temporary myocardial ischemia and hypoxia due to an increase in the myocardial load resulting from a fixed severe stenosis of the coronary artery. Its’ characteristics include paroxysmal pressure pain or tightness in the prothorax, primarily retrosternal pain, which can radiate to the precordium and upper left ulna. It often occurs during physical exertion and lasts for several minutes. Traditional Chinese Medicine (TCM) has unique advantages in treating this disease due to holistic, dynamic and dialectical system of thought regarding life and diseases. Clinical efficacy is the basis for the survival and development of Traditional Chinese Medicine. Scientifically evaluating the clinical efficacy of such TCM treatments is of great importance for promoting its’ modernization and internationalization. In this study, we aimed to observe the therapeutic effects of Compound Salvia Droplet Pills on patients with SAP (Qi deficiency and blood stasis), as shown by a standardized clinical study on the treatment of SAP by means of supplementing qi and activating blood circulation by taking TCM treatments for CHD, thereby providing a practical and valuable clinical treatment approach. 

Methods 
A randomized, controlled trial was designed to evaluate the efficacy and safety of Compound Salvia Droplet Pills for the treatment of SAP.
A proposed total of 60 patients with SAP (Qi deficiency and blood stasis type) are to be entered into the study. 
The patients shall be randomly assigned to treatment groups (compound Salvia Droplet Pills, 10 pills/time, 3 times a day, + aspirin enteric - coated tablets 100mg/time, once a day) or the control group (compound Salvia Droplet Pills mimetics, 10 pills/time, 3 times a day, + aspirin enteric - coated tablets 100mg/time, once a day), duration of 28 ±1, and follow-up for 14 ± 3 days. 
Primary outcome measures: angina pectoris symptom scores and TCM syndrome scores. 
Secondary outcome measures: ECG, incidence and mortality of cardiovascular events, etc. 

Discussion 
This is a randomized controlled trial for Compound Salvia Droplet Pills to treat SAP on the basis of conventional therapy, to preliminarily evaluate the efficacy in the treatment of patients with SAP (angina symptoms, signs and reducing the use of vasodilator drugs, etc.), and follows up on the short -term prognosis of patients to provide clinical evidence for the use of compound Salvia Droplet Pills in patients with SAP.

Discussion This is a randomized controlled trial for Compound Salvia Droplet Pills to treat SAP on the basis of conventional therapy, to preliminarily evaluate the efficacy in the treatment of patients with SAP (angina symptoms, signs and reducing the use of vasodilator drugs, etc.), and follows up on the short -term prognosis of patients to provide clinical evidence for the use of compound Salvia Droplet Pills in patients with SAP.

Background
Coronary Heart Disease (CHD) refers to a heart disease from vascular stenosis or occlusion caused by coronary artery atherosclerosis or myocardial ischemia and hypoxia or necrosis caused by coronary functional changes (spasms) [1]. CHD is a common cardiovascular disease. In modern industrialized countries, the number of deaths caused by CHD accounts for approximately one third of all deaths. With the social and economic development, people's living habits and lifestyle have undergone tremendous changes in China; with an increasing aging trend, so too the incidence of CHD will increase year by year. According to the statistics from the Ministry of Health, there were more than 500, 000 deaths due to CHD at the beginning of this century, and in 2004, the number of deaths attributed to CHD accounts for 50% of total number of heart disease deaths. CHD has become one of the main diseases which poses a threat to people's health in China.
Therefore, active prevention and treatment of CHD is a major research topic that challenges medical practitioners throughout the world.
The names "CHD" and "angina pectoris" do not exist in Traditional Chinese Medicine, but physicians from all ages have given further elaborations on their syndromes, etiologies, pathogenesis, and relevant prevention and treatment measures, which have mainly been dispersed throughout the "heartache", "chest obstruction", "cardiac obstruction" and "severe palpitation" range etc. At present, CHD is mainly classified within the scope of a chest obstruction and heartache etc., forming a unique system of syndrome differentiation in Chinese medicine regarding CHD. TCM's consensus on the pathogenesis of CHD and Stable Angina Pectoris, is that it is due to an intrusion of cold evils, improper diet, emotional disorder, and physical disability, etc. These pathogenic factors will cause diseases in isolation, or cause imbalances in the Qi and blood, yin and yang, to produce a variety of pathological changes, i.e. cold coagulation, phlegm stasis, qi stagnation, blood stasis, and eventually a dysfunction of the internal organs. The real syndrome is primarily phlegm and blood stasis, while the deficiency syndrome is primarily due to the relationship with the internal organs such as a cardiac and renal yin deficiency, cardiac and renal yang deficiency, cardiac qi deficiency with blood stasis, and phlegm stasis. The characteristics of pathogenesis are "chronic diseases intruding into collaterals, heart vessel blockage stasis or qi stagnation and blood stasis".
TCM has unique advantages in treating this disease due to its' holistic, dynamic and

Objective
The objective of this study is to observe the therapeutic effect of Compound Salvia Droplet Pills on the heart function and TCM syndromes of patients with CHD with stable angina pectoris (Qi deficiency and blood stasis).

Methods And Design Program Design
This study is a randomized, single-blind, controlled trial. All cases were outpatients. Sixty subjects were randomly allocated to treatment and control groups. The specific technical route is as shown in Figure 1.

Subjects Sample Size
This study was a clinical pilot trail. According to expert suggestions, the total sample size was set at 60 cases (the case dropout rate was controlled to within 20% during the trial), of which 30 cases were allocated to the treatment group and 30 cases to the control group.
The formula for calculating sample size is as follows: Diagnostic Criteria (1) CHD Diagnostic Criteria: 1) Has a history of myocardial infarction, with or without receiving revascularization (PCI or CABG) treatments; 2) Coronary angiography or coronary CTA indicates at least one major branch of the lumen diameter stenosis has narrowed by over 50%, with or without receiving revascularization treatments.
Diagnosis can be made if patient conforms with one of the above criteria.
(2) SAP Diagnostic Criteria With reference to the Symposium of National Integrative Medicine Prevention and Treatment of Coronary Heart Disease, Angina and Arrhythmia's "Reference Standard for Diagnosis of Coronary Heart Disease" [4] revised in September 1979, this disease was graded by referring to "Guidelines for the Diagnosis and Treatment of Chronic SAP" [5].  In addition, the incidence conditions of end-point events were observed to analyze the incidence of cardiovascular events and rehospitalization rate.

Safety Indices
Safety checks included vital signs, physiochemical examinations and evaluation of adverse events. The measured vital signs included blood pressure and heart rate; physiochemical examinations included routine blood, urine, stools and occult blood, hepatic and renal functions. The routine stool and occult blood trails were adopted to prevent the use of drugs for anti-platelet aggregation and anticoagulants, which may lead to gastrointestinal bleeding.
Adverse events were recorded during the treatment phase. The prognosis of adverse events was observed until the adverse reactions disappeared or were alleviated.

Data Collection
We collected three types of data including basic information (gender, age, previous medical history, medication, etc.), disease evaluation (angina pectoris symptom score, TCM syndrome score) and physiochemical trails (ECG, coagulation, etc.). For specific items and interviews, refer to Table 1.
The data and information were entered into the medical records and case report forms by the researchers. The medical records were designed giving consideration to facilitating the researchers entering of data and data traceability. the original patient's name, contact information, physiochemical trail reports, etc. were retained; the case report forms were designed to facilitate data entry; patients personal information was kept confidential and the patients were distinguished by code.

Recruitment
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