To Evaluate the Efficacy and Safety of Xinnaoning Capsule in Treating Chronic Stable Angina Pectoris (Qi Stagnation and Blood Stasis Syndrome) : a Randomized, Double-blind, Parallel Controlled, Multi-center Clinical Study
Phase: PHASE4
Conditions: Chronic Stable Angina Pectoris, Qi Stagnation and Blood Stasis Syndrome
Sponsor: Beijing Duheng for Drug Evaluation and Research Co., Ltd. (DDER)

 Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001 
                                                  
 Medicine Character ：Z20025697 
 
 
Clinical trial scheme of 
Xinnaoning Capsule 
A randomized, double-blind, parallel-controlled, 
multi-center clinical trial was conducted to evaluate 
the efficacy and safety of Xinnaoning capsule in the 
treatment of chronic stable angina pectoris (Qi 
stagnation and blood stasis syndrome). 
 
 
 
 
 
Unit in charge of clinical trials: Xiyuan Hospital, Chinese 
Academy of Traditional Chinese Medicine 
Bidder: Guizhou Jingcheng Pharmaceutical Co., Ltd. 
Statistical Unit: Beijing Huaxia Zhongchuang Medical 
Research Institute 
Contract Research Organization: Beijing Duheng for Drug 
Evaluation and Research Co., Ltd. (DDER) 
Version number: V1.1 
Version date: January26， 2018 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                         
Version number：V1.1   Version date：January 26，2018 
Confidentiality statement 
This clinical trial scheme is a confidential document, which is only for the use of Xinnaoning 
capsule clinical trial researchers and the ethical committee of the experimental unit, and should not be 
disseminated or leaked. The reader agrees that the contents of this document shall not be disseminated 
and published without the written approval of the applicant, Guizhou Jingcheng Pharmaceutical Co., 
Ltd. The applicant requests that this document be submitted to the authorized representative of the 
National Drug Review and Clinical Trial Institutions in case of confidentiality. 
 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                         
Version number：V1.1   Version date：January 26，2018   
 
Clinical trial scheme of Xinnaoning Capsule- Multiparty 
statement 
1. Bidders  
We have participated in discussions to revise this clinical trial program and will 
conscientiously fulfill the bidder's responsibilities in accordance with the "Quality 
Management Standards for Drug Clinical Trials". Responsible for initiating, applying, 
organizing, funding and investigating the clinical trial, especially providing insurance 
for subjects who suffer from test-related damage or death in the clinical trial, 
undertaking financial compensation for treatment, and providing legal guarantees to 
researchers. 
Bidder: Guizhou Jingcheng Pharmaceutical Co., Ltd. 
Address: No. 158 Gaoxin Road, Wudang District, Guiyang City  Zip code：550002 
Project Leader：Minghuan Luo                  Telephone：13891950813 
2. Clinical trial institute 
I will conscientiously fulfill the responsibilities of researchers in accordance 
with the "Standards for Quality Management of Drug Clinical Trials".             
I have received the Researcher's Manual. I know the testing process of the 
experimental drug. I have been informed that the updated Researcher's Manual will be 
received in time.             
I have read this program, and this experiment will be conducted in accordance 
with the moral, ethical and scientific principles stipulated in the Helsinki Declaration 
and the Chinese GCP. I agree to carry out this clinical trial in accordance with the 
design and provisions of this program.             
I will be responsible for making clinically relevant medical decisions to ensure 
that patients receive timely and appropriate treatment when adverse reactions occur 
during the trial. I know the requirements for correct reporting of serious adverse events, 
and I will record and report these events as required.             
I guarantee that the data will be true, accurate, complete and timely in the case 
report form. I will accept the inspectors or inspectors dispatched by the applicants and 
the inspections, inspections and inspections of the drug regulatory authorities to ensure 
the quality of clinical trials.             
I agree that the test results will be used for drug registration and publication. I 
will provide a curriculum vitae to the Ethics Committee and possibly to the 
Pharmaceutical Administration for review before the start of the experiment.                     
 
Test Responsible Unit: Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine 
Address: No. 1 Xiyuan Playground, Haidian District, Beijing   
Zip code：100091  

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                         
Version number：V1.1   Version date：January 26，2018   
Major Researcher：Fengqin Xu                        Telephone：010-62835113 
3. Contract Research Organization 
I will conscientiously perform the duties of the inspector in accordance with the 
provisions of the GCP.             
I have read this plan, and I will conscientiously perform the duties of supervisor 
in accordance with the "Standards for Quality Management of Drug Clinical Trials". I 
will ensure that the rights and interests of subjects in clinical trials are guaranteed, and 
the data recorded and reported in trials are true, accurate and complete. To ensure that 
the trials follow the approved program, the "Quality Management Standards for Drug 
Clinical Trials" and relevant regulations. 
 
Contract Research Organization: Beijing Duheng for Drug Evaluation and Research 
Co., Ltd. (DDER) 
Address: Building No.2603,2,2,Chaoyang North Road No.8,Chaoyang District,Beijing 
100024,P.R.China 
Zip code:100024 
Project Leader:Chunsheng Qiao                       Telephone: 010-58462584 
 
4. Data management and statistical analysis 
I will conscientiously perform the duties of statisticians in accordance with the 
"Standards for Quality Management of Drug Clinical Trials".             
Statistical Unit: Beijing Huaxia Zhongchuang Medical Science and Technology 
Research Institute Address: No. 401 Building, 28 Guangqu Road, Chaoyang District, 
Beijing.  
Zip code: 100022             
Statistician: Wangjun Liu                            Telephone: 010-58409120 
  

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                         
Version number：V1.1   Version date：January 26，2018   
                              Catalog 
ABBREVIATION ...............................................................................................................................1 
CLINICAL TRIAL SCHEME OF XINNAONING CAPSULE·ABSTRACT  ...................................2 
CLINICAL TRIAL SCHEME OF XINNAONING CAPSULE·MAIN BODY .................................6 
1. 
TEST BACKGROUND ...........................................................................................................6 
2. EXPERIMENTAL PURPOSE ......................................................................................................10 
3. EXPERIMENTAL DESIGN .........................................................................................................10 
3.1 INTEGRAL TEST DESIGN .................................................................................................................. 10 
3.2 SAMPLE SIZE .................................................................................................................................. 11 
4. SUBJECT SELECTION AND WITHDRAWAL .........................................................................12 
4.1  DIAGNOSTIC CRITERIA OF WESTERN MEDICINE ........................................................12 
4.1.1 DIAGNOSTIC CRITERIA FOR CORONARY HEART DISEASE .......................................12 
REFERRING TO THE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF 
CHRONIC STABLE ANGINA ISSUED BY THE CHINESE MEDICAL ASSOCIATION IN 2007, 
THE DIAGNOSIS OF STABLE ISCHEMIC HEART DISEASE BY 
2012ACP/ACCF/AHA/AATS/PCNA/STS: CLINICAL PRACTICE GUIDELINES, AND THE 
GUIDELINES FOR THE MANAGEMENT OF STABLE CORONARY ARTERY DISEASES 
ISSUED BY 2013 ESC, WE CAN DIAGNOSE CORONARY HEART DISEASE BY 
CONFORMING TO ANY OF THE FOLLOWING: ........................................................................12 
4.1.2 Diagnostic criteria for angina pectoris ................................................................................ 12 
4.1.3 Classification criteria for angina pectoris ........................................................................... 13 
4.2. DIFFERENTIATION STANDARD OF TRADITIONAL CHINESE MEDICINE ............................................ 14 
4. 3. ANGINA PECTORIS INTEGRAL SCORING METHOD ......................................................................... 15 
（ANGINA PECTORIS） ....................................................................................................................... 15 
4. 4. TCM SYNDROME INTEGRAL SCORING METHOD .......................................................................... 15 
4. 5 SEATTLE ANGINA QUESTIONNAIRE,SAQ。 .................................................................................. 17 
4.6 PARTICIPANT SELECTION CRITERIA ................................................................................................. 17 
4.7 SUBJECT EXCLUSION CRITERIA ...................................................................................................... 17 
4.8 EXFOLIATION EXCLUDED CASES .................................................................................................... 18 
4.8.1 The withdrawal of the researcher's decision ........................................................................ 18 
4.8.2 Subjects withdraw spontaneously ......................................................................................... 18 
4.8.3 Criteria for excluding cases ................................................................................................. 19 
4.9 CONDITIONS FOR DISCONTINUATION OF RESEARCH ....................................................................... 19 
5. DOSAGE REGIMEN ...................................................................................................................19 
5.1  ADMINISTRATION METHOD .......................................................................................................... 19 
5.2 PHARMACEUTICAL INFORMATION FOR TESTING DRUGS ................................................................ 20 
5.3 PHARMACEUTICAL PACKAGING FOR TESTING DRUGS .................................................................... 21 
5.4 CASE ALLOCATION METHOD ........................................................................................................... 21 
5.5 DOSE SELECTION AND ADMINISTRATION TIME ................................................................................ 21 
5.6 BLIND METHOD .............................................................................................................................. 21 
5.7 DRUG DISTRIBUTION AND PRESERVATION ...................................................................................... 24 
5.8 DRUG COUNTING AND DRUG COMPLIANCE JUDGMENT OF SUBJECTS .............................................. 24 
5.9 REGULATIONS ON COMBINED USE OF DRUGS .................................................................................. 25 
1. IN ADDITION TO EXPERIMENTAL MEDICATION, NITROGLYCERIN TABLETS CAN BE USED TO ALLEVIATE 
SYMPTOMS WHEN ANGINA ATTACKS. FOR DRUGS ALREADY USED TO TREAT CORONARY HEART DISEASE 
BEFORE INCLUSION, SUCH AS ANTIPLATELET DRUGS, ANGIOTENSIN-CONVERTING ENZYME INHIBITORS 
(ACEI) OR ANGIOTENSIN II RECEPTOR ANTAGONISTS (ARB), STATINS, CALCIUM ANTAGONISTS, 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                         
Version number：V1.1   Version date：January 26，2018   
BETA-BLOCKERS AND LONG-ACTING NITRATES, THE ORIGINAL VARIETIES AND DOSAGES CAN BE 
CONTINUED WITHOUT ADJUSTMENT. DURING THE STUDY PERIOD, IT IS FORBIDDEN TO ADD ANY OTHER 
CHINESE AND WESTERN MEDICINES WHICH HAVE THERAPEUTIC EFFECTS ON ANGINA PECTORIS OF 
CORONARY HEART DISEASE. ................................................................................................................. 25 
2. FOR THE ORIGINAL AND EMERGING DISEASES REQUIRING DRUG TREATMENT, THE DRUG 
COMBINATION SHOULD BE RECORDED IN THE MEDICAL RECORD AND CRF IN DETAIL, INCLUDING THE 
GENERIC NAME OF THE DRUG, DOSAGE AND METHOD OF ADMINISTRATION, THE STARTING TIME OF 
DRUG USE AND THE REASONS FOR ITS USE. .......................................................................................... 25 
6. OBSERVATION ITEMS ...............................................................................................................25 
6.1 GENERAL RECORD ITEMS ............................................................................................................... 25 
6.2 OBSERVATION INDEX ...................................................................................................................... 25 
6.2.1 General observation indicators ............................................................................................ 25 
6.2.2 Effectiveness indicators ........................................................................................................ 25 
6.2.3 
Safety indicators ........................................................................................................... 26 
6.2.4 Other observational indicators ............................................................................................ 26 
6.3 OBSERVATION WINDOW .................................................................................................................. 26 
6.4 TEST PROCEDURE ........................................................................................................................... 26 
6.4.1 Visit 1-Import Period (-14±2 days) ....................................................................................... 26 
6.4.2 Visit 2 - before treatment (0 days) ........................................................................................ 26 
6.4.3 Visit 3 (4 weeks ± 4 days)  ..................................................................................................... 27 
6.4.4 Visit 4 (8 weeks ±4 days) ） .................................................................................................. 27 
6.4.4 Visit 5 (12 weeks ± 4 days)  ................................................................................................... 27 
7. OBSERVATION OF ADVERSE EVENTS ..................................................................................28 
7.1 RECORDING OF ADVERSE EVENTS .................................................................................................. 28 
7.1.1 Definition of Adverse Event (AE) ......................................................................................... 28 
7.1.2 Judgment of Causality between Adverse Events and Testing Drugs ..................................... 28 
7.1.3 Recording and reporting of adverse events .......................................................................... 30 
7.1.4 Treatment of subjects with adverse events ............................................................................ 30 
7.2 DEALING WITH SERIOUS ADVERSE EVENTS ................................................................................... 30 
7.2.1 Definition of Serious Adverse Event ..................................................................................... 30 
7.2.2 Treatment and Report of Serious Adverse Events ................................................................. 30 
7.2.3 Recording of serious adverse events .................................................................................... 31 
7.3 DISASSEMBLY AND PROCESSING OF EMERGENCY LETTERS ........................................................... 31 
7.4 FOLLOW-UP OF UNREMITTED ADVERSE EVENTS ............................................................................. 31 
8. EVALUATION OF CLINICAL TRIALS .....................................................................................31 
8.1 EVALUATION OF CLINICAL EFFECTIVENESS .................................................................................... 31 
8.1.1 Criteria for evaluation of main therapeutic indicators ........................................................ 31 
8.1.2 Evaluation criteria of secondary efficacy indicators ............................................................ 32 
8.2 CLINICAL SAFETY EVALUATION ...................................................................................................... 32 
9. DATA MANAGEMENT ..............................................................................................................33 
10. STATISTICAL ANALYSIS ........................................................................................................33 
10.1 ANALYTICAL DATA SET ................................................................................................................ 33 
10.2 STATISTICAL ANALYSIS METHOD .................................................................................................. 34 
10.2.1 Statistical description ......................................................................................................... 34 
10.2.2 Statistical expression .......................................................................................................... 34 
10.2.3 Statistical analysis content ................................................................................................. 34 
11. QUALITY CONTROL AND GUARANTEE OF CLINICAL TRIALS ....................................35 
11.1 RECORDS OF CLINICAL TRIALS ..................................................................................................... 35 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                         
Version number：V1.1   Version date：January 26，2018   
11.2 MANAGEMENT OF EXPERIMENTAL DRUG USE ............................................................................... 36 
11.3 TRAINING RESEARCHERS ............................................................................................................. 36 
11.4 MEASURES TO IMPROVE OBSERVATION CONSISTENCY ................................................................. 36 
11.5 LABORATORY QUALITY CONTROL REQUIREMENTS ...................................................................... 37 
11.6 SURVEILLANCE OF CLINICAL TRIALS ............................................................................................ 37 
12. ETHICAL PRINCIPLES ............................................................................................................37 
13. DATA PRESERVATION .............................................................................................................38 
14. MODIFICATION OF THE SCHEME ........................................................................................38 
15. ORGANIZATION AND MANAGEMENT OF TESTS .............................................................38 
15.1 PROGRESS AND ARRANGEMENT OF TEST WORK .......................................................................... 39 
SIGNATURE PAGE FOR PARTICIPATING CENTER RESEARCHERS ....................................................40 
BIDDER'S SIGNATURE PAGE ............................................................................................................41 
INSPECTOR'S SIGNATURE PAGE ......................................................................................................44 
ENCLOSURE 1 CORONARY HEART DISEASE SUBJECT SPORTS MANUAL CORONARY 
HEART DISEASE SUBJECT SPORTS MANUAL ........................................................................46 

 Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001 
 Version number：V1.1   Version date：January 26，2018                                                                         
1
Abbreviation 
Abbreviation 
English full name 
Chinese 
AE 
Adverse Event 
不良事件 
ALP 
Alkaline Phosphatase 
碱性磷酸酶 
ALT 
Alanine Aminotransferase 
丙氨酸氨基转移酶/谷丙转氨酶 
AST 
Asparate Aminotransferase 
门冬氨酸氨基转移酶/谷草转氨酶 
BUN 
Blood Urea Nitrogen 
尿素氮 
CFDA 
China Food and Drug 
Administration 
国家食品药品监督管理总局 
HCY 
Homocysteine 
血同型半胱氨酸 
Cr 
Creatinine 
肌酐 
CRF 
Case Report Form 
病例报告表 
CRO 
Contract Research Organization 
合同研究组织 
FAS 
Full Analysis Set 
全分析集 
GCP 
Good Clinical Practice 
药物临床试验质量管理规范 
GGT/γ-GT 
γ-Glutamyl Transpeptadase 
谷氨酰转肽酶 
ITT 
Intention to Treat 
意向性治疗 
PPS 
PerProtocol Set 
符合方案集 
QA 
Quality Assurance 
质量保证 
QC 
Quality Control 
质量控制 
SAE 
Serious Adverse Event 
严重不良事件 
SOP 
Standard Operating Procedures 
标准操作程序 
SS 
Safety Analysis Set 
安全性数据集 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Clinical trial scheme of Xinnaoning capsule·Abstract 
Title 
To evaluate the efficacy and safety of Xinnaoning Capsule in treating 
chronic stable angina pectoris (Qi stagnation and blood stasis syndrome) 
with placebo as control: a randomized, double-blind, parallel controlled, 
multi-center clinical study 
Purpose 
To evaluate the efficacy and safety of Xinnaoning Capsule in the 
treatment of chronic stable angina pectoris (Qi stagnation and blood 
stasis syndrome) 
Experimen
-tal design 
A randomized, double-blind, placebo-controlled, multi-center, efficacy 
test design is used. 
Subject 
population 
Subjects with chronic stable angina pectoris (qi stagnation and blood 
stasis syndrome) 
      
Inclusion 
Criteria 
1. Refer to the Guidelines for Diagnosis and Treatment of Chronic 
Stable Angina issued by the Chinese Medical Association in 2007, 
2012ACP/ACCF/AHA/AATS/PCNA/STS (Guidelines for Diagnosis 
and Management of Stable Ischemic Heart Disease: American Heart 
Foundation/American Heart Association/American Medical 
Association/American Thoracic Surgery Association/American 
Association for Cardiovascular Preventive Nursing/American 
Association for Cardiovascular Angiography and Intervention/American 
Thoracic Association The Diagnosis of Stable Ischemic Heart Disease: 
Guidelines for Clinical Practice, Guidelines for the Management of 
Stable Coronary Artery Diseases in 2013 ESC, which can diagnose 
coronary heart disease in accordance with any of the following:         
(1) Has a clear history of old myocardial infarction, or PCI history, or 
bypass history;            
(2) Coronary angiography (results indicate at least one coronary artery 
stenosis with stenosis (>50%) or coronary CTA suggests stenosis with 
stenosis (>50%).             
2. Those who met the diagnostic criteria of chronic stable angina 
pectoris: those who had a history of angina pectoris more than 1 month 
and had no significant changes in the degree, frequency, nature and 
inducing factors of angina pectoris;             
3. The severity of angina pectoris of the Canadian Cardiovascular 
Society (CCS) was classified as Grade I to Grade III, and angina 
pectoris occurred more than twice a week.             
4. The syndrome differentiation of TCM is Qi stagnation and blood 
stasis syndrome.             
5. Age ranges from 30 to 79 years old.             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
6. Sign the informed consent. 
Exclusion 
Criteria 
1. Severe cardiopulmonary insufficiency (grade III, IV, severe abnormal 
pulmonary function);             
2. Poor control of hypertension (systolic blood pressure (> 160 mmHg) 
or diastolic blood pressure (> 100 mmHg) after treatment;            
3. Complicated with liver and kidney function damage, ALT, AST (> 1.5 
times of the upper limit of normal value), or Cr (> the upper limit of 
normal value), combined with hematopoietic system and other serious 
primary diseases;             
4. Acute myocardial infarction within 3 months after interventional 
therapy;             
5. Cardiac pacemaker;             
6. Pregnancy, lactation or pregnancy planning;             
7. Anaphylactic constitution or allergic to known ingredients of research 
drugs;             
8. Chest pain caused by other causes (moderate anemia, 
hyperthyroidism, etc.)             
9. Those who participated in other clinical drug trials within one month;  
10. According to the judgement of the researchers, it is not advisable to 
participate in clinical researchers.             
11. Other factors affecting ST-T changes in ECG, such as myocardial 
hypertrophy, left bundle branch block, etc. 
Sample 
size 
According to the statistical requirements, the sample 
size was estimated. The main effect index was the curative 
effect of angina pectoris symptoms treated for 12 weeks. 
According to the literature, the total effective rate of basic 
treatment plus placebo was 67.5%, and the total effective rate 
of basic treatment plus experimental drugs was predicted to 
be 84.3%.set α=0.05，1-β=0.2，according to the experimental 
group: control group = 1:1 set up group, 
        P1×(100-P1)+P2×(100-P2) 
n＝ － －－－－－－－－－－－－－－ ×f(a，b) 
(P2-P1)
2 
The minimum sample size to meet the statistical requirements was 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
98.4 cases in each group, and the dropping rate was not more than 20%, 
120 cases in each group, a total of 240 cases. 
Effectiven-
ess     
evaluating 
indicator 
1. Main outcome measures: The curative effect of angina pectoris;       
2. Secondary indicators: curative effect of TCM syndromes, grading 
changes of severity of angina pectoris, changes of attack times per week, 
nitroglycerin dosage, score of Seattle Angina Scale and incidence of 
cardiovascular events, blood HCY (blood homocysteine). 
Safety   
evaluating 
indicator 
1. Possible adverse reaction symptoms.             
2. General physical examination items, such as body temperature, pulse, 
breathing, blood pressure, etc.             
3. Laboratory examination: blood routine, urine routine + microscopy, 
stool routine + Occult blood, liver and kidney function (ALT, AST, 
ALP, GGT, TBIL, BUN, Cr), blood lipid (HDL-C, LDL-C, TG, 
CH), blood coagulation. 
Dosage 
regimen 
The induction period was 2 weeks and the treatment period was 12 
weeks.             
Introducing period: 2 weeks, time window (+2 days).            
Introducing drug regimen: Both groups were given Xinnaoning capsule 
Simulator 3 capsules per time, 3 times per day, orally, after meals.       
Course of treatment: 12 weeks, time window (+4 days).            
Test group: Xinnaoning capsule, 3 capsules per time, 3 times per day    
Control group: Xinnaoning capsule Simulator 3 tablets per time, 3 times 
per day, oral, after meals. 
Combined 
medication 
1. In addition to experimental medication, nitroglycerin tablets can be 
used to alleviate symptoms when angina attacks. For drugs already used 
to treat coronary heart disease before inclusion, such as antiplatelet 
drugs, angiotensin-converting enzyme inhibitors (ACEI) or angiotensin 
II receptor antagonists (ARB), statins, calcium antagonists, 
beta-blockers and long-acting nitrates, the original varieties and dosages 
can be continued without adjustment. During the study period, it is 
forbidden to add any other Chinese and Western medicines which have 
therapeutic effects on angina pectoris of coronary heart disease.         
2. For the original and emerging diseases requiring drug treatment, the 
drug combination should be recorded in the medical record and CRF in 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
detail, including the generic name of the drug, dosage and method of 
administration, the starting time of drug use and the reasons for its use. 
Course of 
treatment 
The induction period was 2 weeks and the medication period was 12 
weeks. 
Experimen
-tal 
progress 
The preliminary plan is to complete all clinical trials within 18 months 
from the arrival of the drug in the hospital. 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Clinical trial scheme of Xinnaoning Capsule·main body 
1. Test background 
Coronary heart disease (CHD) is the most harmful cardiovascular disease 
worldwide. It is also the first cause of hospitalization and death of adult heart disease 
in China. Its morbidity and mortality are still on the rise. Active treatment and 
prevention of CHD is an important subject in medical research.                
Coronary heart disease angina pectoris is a kind of heart disease caused by 
myocardial ischemia and anoxia caused by coronary atherosclerosis. It belongs to the 
category of "chest obstruction" and "heartache" in traditional Chinese medicine. The 
occurrence of angina pectoris is mostly related to cold pathogenic invasion, improper 
diet, emotional disorder, old body deficiency and other factors. The pathogenesis of 
"Chest Bi" is deficiency and reality, which is actually cold coagulation, Qi stagnation, 
blood stasis, phlegm obstruction, obstruction of chest Yang and heart vein; deficiency 
is deficiency of heart, spleen, liver and kidney, heart and vein dystrophy. One of its 
common pathogenesis is stagnation of Qi and blood stasis, blockage of blood vessels, 
so it should be treated by activating blood circulation and removing blood stasis, 
dredging channels and collaterals, as well as tranquilizing Qi and tranquilizing spirit, 
in order to achieve the goal of blood stasis to remove new life and nourish the blood 
vessels of viscera and viscera.             
Xinnaoning Capsule (Z20025697), produced by Guizhou Jingcheng 
Pharmaceutical Co., Ltd., is mainly composed of Ginkgo biloba leaves, Salvia 
miltiorrhiza, Ginger fruit, Euonymus microphylla and Allium macrophylla. It has the 
functions of activating blood circulation, promoting Qi circulation, dredging 
collaterals and relieving pain. Chest stuffiness, dizziness, vertigo, symptoms: chest 
tightness, tingling, palpitation restlessness, dizziness and dizziness, as well as 
coronary heart disease, cerebral arteriosclerosis see the above symptoms. Xinnaoning 
Capsule has not had any adverse reactions for many years after it was put on the 
market. 
Pharmacological research 
Xinnaoning Capsule, in which Ginkgo biloba leaf is the monarch medicine, 
Ginkgo biloba leaf promotes blood circulation and removes blood stasis, relieves pain, 
is used for coronary heart disease, angina pectoris and blood stasis syndrome caused 
by hyperlipidemia. Salvia miltiorrhiza and Ginger fruit are the main medicines. 
Among them, Salvia miltiorrhiza has good effect on promoting blood circulation and 
removing blood stasis, cooling blood and tranquilizing mind, and has good effect on 
all diseases caused by blood stasis, especially on heart and brain blood stasis 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
syndrome. In addition, Salvia miltiorrhiza can cool blood and calm the nerves. It has 
good effect on palpitation and insomnia in the above diseases. Ginger has the function 
of dispelling cold in warmth, regulating qi and relieving pain. The combination of the 
two medicines can not only promote blood circulation, but also regulate qi. Qixing 
can promote blood circulation and remove blood stasis. Populus microphylla and 
Allium macrophylla were used as adjuvants. Effectiveness of Euonymus microphylla 
is promoting qi and blood circulation, dredging collaterals and relieving pain. It is 
used for chest pain, heart pain and coronary heart disease caused by qi stagnation and 
blood stasis. The effect of Xiebai can regulate qi, broaden chest, promote Yang and 
disperse. It is used to treat thoracic paralysis and heartache. "Compendium of Materia 
Medica" says that it can "treat Shaoyin disease, syncope, diarrhea, and chest pain. 
These two medicines have the functions of regulating qi, promoting blood circulation 
and strengthening the functions of activating blood circulation, regulating qi and stasis 
of other medicines. The above medicines are mainly used to promote blood 
circulation, supplemented by regulating qi. Regulating Qi helps to promote blood 
circulation. Promoting blood circulation helps to promote qi circulation, blood stasis, 
meridians and collaterals, and all kinds of symptoms go by themselves to treat chest 
pain, stroke, stroke, dizziness and other diseases caused by qi stagnation and blood 
stasis, blockage of blood vessels.             
Modern pharmacology shows that flavonoids and terpene lactones are effective 
components of Ginkgo biloba leaves. Experiments show that flavonoids and terpene 
lactones are beneficial to blood vessel and brain metabolism and inhibit platelet 
activating factor. Ginkgolides and ginkgolides can significantly improve the oxygen 
tolerance of brain cells and enhance local brain flow. Ginkgolides have a strong 
neuroprotective effect. Salvia miltiorrhiza can inhibit platelet aggregation, dilate 
coronary artery, increase the opening of collateral circulation, improve myocardial 
hypoxia, and also have good scavenging effect of oxygen free radicals. The 
experiment of Gingeria officinalis L. showed that Gingeria officinalis L. oil could 
reduce the area of myocardial infarction and the level of serum lactate dehydrogenase 
after myocardial infarction. It has protective effect on myocardial ischemia. It can also 
slow down the systolic and diastolic blood pressure, slow down the heart rate and 
reduce the cardiac output. Allium sibiricum can inhibit platelet aggregation and 
reduce serum lipid peroxide and blood lipid. Euonymus microphylla can dilate 
coronary artery, improve myocardial ischemia and reduce oxygen consumption. 
Previous clinical trials 
1. To observe the clinical effect of Xinnaoning Capsule on angina pectoris 
of coronary heart disease of qi stagnation and blood stasis type. 
    From February 2011 to October 2011, Xinnaoning was observed in 309 Hospital 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
of PLA. Methods: 182 patients with angina pectoris of qi stagnation and blood stasis 
type were randomly divided into treatment group (102 cases) and control group (80 
cases). The control group was treated with routine treatment group (isosorbide 
mononitrate tablets, aspirin enteric-coated tablets, 100 mg each time, once a day). The 
treatment group was treated with routine treatment in the control group. Xinnaoning 
capsule was taken three times a day for 8 weeks. The results are as follows:                   
Table1 Comparison of improvement effect of angina pectoris between two groups n (%) 
    Group     n   Markedly effective  effective   invalid  total effective rate 
   Test      102       34（33.3）       52（51）    16（15.7）          86（84.3） 
Control     80        26（32.5）     28（35）    24（32.5）          56（67.5） 
There were significant differences between groups.，P＜0.05 
 
Table2 Comparison of the curative effect of TCM syndromes improvement between two 
groups before and after treatment 
Symptom    Group        n     ME     effetive       invalid      TER（%） 
Chest pain       T        102      36        56             12        92（92.2） 
             C        80       19        44              17        63（78.7） 
Chest tightness  T        102      42        50              10        92（90.2） 
         C        80       20        42              18        62（77.5） 
palpitation     T        102      34        54              14        88（86.2） 
         C        80       18        43              19        61（76.3） 
pant          T        102      32        49              21        81（79.4） 
             C        80       20        35              25        55（68.7） 
dizzy         T        102      36        54              12          90（88.2） 
C        80       15        23              42          38（47.5） 
headache       T       102      32         47              22          79（77.4） 
         C         80       7        27              46           34（42） 
Note: Chest pain, palpitation and other symptoms of the two groups were 
significantly improved after treatment. The treatment group had significant effect 
on improving chest tightness, chest pain, dizziness, headache and other clinical 
symptoms, compared with the control group,P＜0.01.T=test group,C=control roup,ME= 
Markedly effective,TER= total effective rate 
                           
 
Table3 Comparison of ECG changes before and after treatment in two groups 
Group         n     ME     effective     invalid          TER（%） 
T            102     39        38           25             76（74.5） 
C             80     31        27           22             58 （72.5） 
  Note: After treatment, ECG in both groups improved, but there was no 
significant difference between the two groups. 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
The clinical results showed that the total effective rate of angina pectoris in the 
treatment group was better than that in the control group, especially in improving the 
symptoms of chest pain, chest tightness, dizziness and headache. There were no 
significant changes in blood pressure and heart rate before and after treatment, and no 
obvious adverse reactions during treatment, suggesting that the drug is safe. It is an 
effective and safe drug for the treatment of coronary heart disease and angina pectoris. 
  
2. Evaluation of Xinnaoning Capsule in the Treatment of Angina Pectoris after 
Coronary Stent Implantation  
     From June 2012 to June 2014, the cardiovascular disease center of Xiyuan 
Hospital, Chinese Academy of Traditional Chinese Medicine was studied. Methods: 
160 patients with recurrent angina pectoris after coronary artery stent implantation 
were randomly divided into treatment group (80 cases) and control group (80 cases). 
The course of treatment was 8 weeks. Control group: aspirin enteric-coated tablets 
100mg, once a day, isosorbide mononitrate tablets 20mg, twice a day, atorvastatin 
calcium tablets 20mg, once a day. Treatment group: On the basis of the control group, 
Xinnaoning capsule was added, three capsules each time, three times a day. The 
results are as follows: 
 
     Table 4 Comparison of curative effect of angina pectoris between two groups (%) 
Group          ME           effective     invalid            TER 
T            28（35.00）    41（51.25）  11（13.75）      69（86.25） 
C           19（23.75）    30（37.50）   31（38.75）      49（61.25） 
Note: Compared with the control group, P＜0.05 
Table 5 Comparison of curative effect of TCM syndromes between two groups (%) 
Group 
                      Chest pain 
 ME           effective               invalid          TER 
Test（n=80） 
 26（32.50）     45（56.25） 
 9 （11.25） 
  71（88.75） 
Control（n=80）  19 （23.75）     32（40.00） 
 29（36.25） 
  51（63.75） 
                            
Group 
 Chest tightness 
  ME          effective            invalid               TER 
Test（n=80） 
 26（32.50） 
  46（57.50） 
 8 （10.00） 
     72（90.00） 
Control（n=80） 
 28（22.50）    35（43.75） 
   27（33.75） 
     53（66.25） 
  
Group 
                        pant 
ME          effective            invalid               TER 
Test（n=80） 
 24（32.50） 
  48（60.00） 
  8 （10.00） 
   72（90.00） 
Control（n=80） 
 18（22.50） 
  34（42.50） 
  28（35.00） 
   52（65.00） 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
 Note: Compared with the control group，p＜0.05 
 
Table 6 Comparison of ECG changes after treatment between two groups (%) 
Test   （n=80）  18（22.50）  39（48.75）   23（28.75）   57（71.25） 
Cntrol （n=80）  16（20.00）  35（47.50）   29（36.25）   51（63.75） 
 Note: Compared with the control group，P＜0.05 
Studies have confirmed that Xinnaoning Capsule has a good clinical effect on 
angina pectoris patients after coronary artery stent implantation by improving 
myocardial microcirculation, promoting the opening of collateral circulation, 
inhibiting platelet aggregation, lowering blood lipid and stabilizing platelet. There 
were no significant changes in ECG, blood pressure and heart rate before and after 
treatment, and no obvious adverse reactions during treatment, suggesting that the drug 
is safe.             
For many years after Xinnaoning capsule was put on the market, no adverse 
reactions were recorded in the literature. This experiment completes the clinical trial 
of Xinnaoning Capsule in treating chronic stable angina pectoris (Qi stagnation and 
blood stasis syndrome), and objectively evaluates its clinical efficacy and safety. 
2. Experimental purpose 
To evaluate the efficacy and safety of Xinnaoning Capsule in the 
treatment of chronic stable angina pectoris (Qi stagnation and blood 
stasis syndrome) 
3. Experimental design 
3.1 Integral test design 
The design adopted a placebo parallel control, randomized, double-blind, 
multi-center clinical research design method.             
(1) Multi-center: This multi-center clinical study is expected to be carried out in 
Beijing, Shanghai, Shanxi and Tianjin.             
(2) Random: block random method. SAS 9.1.3 statistical software was used to 
generate random number grouping table according to the number of cases allocated 
and random proportion of participating units.             
(3) Double blindness: the appearance of the control drug is the same as that of 
Group 
      palpitation 
ME          effective            invalid               TER 
Test（n=80） 
22（27.50） 
48（60.00） 
 10 （12.50） 
70（87.50） 
Control（n=80） 
17（21.25） 
34（42.50） 
29（36.25） 
51（63.75） 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
the test drug; the researchers who did not participate in the clinical research compiled 
the blindness of the research drug according to the randomized distribution table 
generated; according to the standardized operation steps of the double blindness 
clinical research, the test drug and the corresponding simulator were repackaged and 
distributed (including emergency letters).             
(4) Control: placebo control. The purpose of this clinical trial is to evaluate the 
efficacy of Xinnaoning Capsule in the treatment of stable angina pectoris, which can 
reflect its "absolute" efficacy and safety, so the placebo control is used in this trial. 
For well-executed clinical trials, placebo-controlled trials can reliably prove the 
efficacy of research drugs, unlike non-inferiority design trials, which need to 
introduce the hypothesis of external efficacy sensitivity and test sensitivity; secondly, 
placebo-controlled clinical trials can clearly study the absolute efficacy of drugs; 
thirdly, they can better differentiate between non-inferiority design trials. Good events 
are caused by drugs or by some potential diseases or other factors; fourthly, they are 
more efficient and require a smaller number of subjects than any other parallel 
controlled study; fifthly, they can reduce the degree of disease improvement expected 
by the subjects and clinical researchers, and increase the ability to detect and study the 
true efficacy of drugs.             
All subjects in this study received basic treatment routinely. Placebo use did not 
affect the normal treatment of subjects, which met the ethical requirements. 
In the experiment, remedial measures such as nitroglycerin (uniformly provided 
by the applicant) will be given after the attack of angina pectoris. Diary cards and 
exercise manual of coronary heart disease will be issued during the clinical trial. 
Researchers should strengthen the observation of the number of attacks of angina 
pectoris and the dosage of nitroglycerin. The rights and interests of the subjects will 
be guaranteed and meet the ethical requirements. 
Usage: When angina pectoris patients attack, take one tablet under the tongue, 
and repeat one tablet every 5 minutes until the pain relieves. If the pain persisted after 
a total of 3 tablets in 5 minutes, the subjects were immediately treated. 
 (5) Sample size: 120 cases in the experimental group and 120 cases in the 
control group. 
3.2 Sample size 
According to the statistical requirements, the sample size was 
estimated. The main effect index was the curative effect of angina 
pectoris symptoms treated for 12 weeks. According to the literature, the 
total effective rate of basic treatment plus placebo was 67.5%, and the 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
total effective rate of basic treatment plus experimental drugs was 
predicted to be 84.3%.Set α=0.05，1-β=0.2，According to the experimental 
group: control group = 1:1 set up group, 
        P1×(100-P1)+P2×(100-P2) 
n＝ － －－－－－－－－－－－－－－ ×f(a，b) 
(P2-P1)
2 
The minimum sample size to meet the statistical requirements was 98.4 cases in 
each group, and the dropping rate was not more than 20%, 120 cases in each group, a 
total of 240 cases. 
 
4. Subject selection and withdrawal 
4.1  Diagnostic criteria of Western Medicine 
4.1.1 Diagnostic criteria for coronary heart disease 
Referring to the Guidelines for the Diagnosis and Treatment of 
Chronic Stable Angina issued by the Chinese Medical Association in 2007, 
the Diagnosis of Stable Ischemic Heart Disease by 
2012ACP/ACCF/AHA/AATS/PCNA/STS: Clinical Practice Guidelines, and the 
Guidelines for the Management of Stable Coronary Artery Diseases issued 
by 2013 ESC, we can diagnose coronary heart disease by conforming to any 
of the following: 
(1) There is a clear history of old myocardial infarction, PCI or bypass.            
(2) Coronary angiography (results indicate that at least one coronary artery is stenosed 
and the lumen is stenosed more than 50%) or coronary CTA indicates that the lumen 
is stenosed more than 50%. 
4.1.2 Diagnostic criteria for angina pectoris 
Referring to the Guidelines for the Diagnosis and Treatment of Chronic Stable 
Angina Pectoris issued by the Editorial Board of the Chinese Journal of 
Cardiovascular Diseases in 2007, the Society of Cardiovascular Diseases of the 
Chinese Medical Association:             
When physical activity or mental stress occurs, coronary artery blood flow can 
not meet the needs of myocardial metabolism, leading to angina attack induced by 
myocardial ischemia. Resting or taking nitroglycerin can alleviate it. Chronic stable 
angina pectoris refers to the degree, frequency, nature and inducing factors of angina 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
pectoris attacks in 1 to 3 months without significant changes in subjects.             
Referring to the International Heart Association and WHO Joint Thematic Group 
on Standardization of Clinical Nomenclature, "Criteria for Nomenclature and 
Diagnosis of Ischemic Heart Disease" [2].              
Tired angina pectoris: Tired angina pectoris is characterized by a brief onset of 
chest pain induced by exercise or other conditions that increase myocardial oxygen 
demand. After rest or sublingual administration of nitroglycerin, the pain often 
disappears rapidly. There are three types of fatigue angina pectoris:             
First-onset fatigue angina pectoris: the course of the disease is less than one month.            
Stable fatigue angina pectoris: the course of the disease is stable for more than one 
month.            
Deteriorating fatigue angina pectoris: The number, severity and duration of fatigue 
induced by the same degree of fatigue suddenly increased.          
Spontaneous angina pectoris: The characteristic of spontaneous angina pectoris is 
that there is no significant relationship between chest pain attack and the increase 
of myocardial oxygen demand. Compared with fatigue angina pectoris, the pain 
generally lasts longer and is more severe, and is not alleviated by nitroglycerin. 
There was no change of enzymes in this type. There were some temporary S-T 
segment depression or T wave changes in ECG. Spontaneous angina pectoris can 
occur alone or in combination with fatigue angina pectoris.             
The frequency, duration and degree of pain in subjects with spontaneous angina 
pectoris may have different clinical manifestations. Sometimes the subjects may 
have sustained chest pain attacks, similar to myocardial infarction, but without 
characteristic changes of electrocardiogram and enzymes. Temporary S-T 
elevation occurs in some subjects with spontaneous angina pectoris, often referred 
to as variant angina pectoris. However, this name cannot be used when the ECG 
pattern is recorded in the early stage of myocardial infarction.             
Initial fatigue angina pectoris, worsening fatigue angina pectoris and spontaneous 
angina pectoris are collectively referred to as "unstable angina pectoris". 
4.1.3 Classification criteria for angina pectoris 
Reference to Canadian Cardiovascular Society (CCS) Angina Severity Classification 
[4] Standard。 
Ⅰ：General physical activity does not cause angina pectoris, such as walking and 
going upstairs, but tension, rapid or sustained exertion can cause the onset of angina 
pectoris. 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Ⅱ：Daily physical activity is slightly restricted. Walking fast or upstairs, 
climbing high, walking after meals or upstairs, walking in cold or wind, and 
emotional excitement can cause angina or only occur within a few hours after waking 
up. It is limited to walk more than 200 meters or climb stairs above one floor at 
normal speed. 
Ⅲ：Daily physical activity is obviously limited, and angina pectoris can occur 
when walking 100-200 m at normal speed or climbing a staircase. 
Ⅳ：Angina symptoms can occur when you are slightly active or at rest.    
This table is cited from the guidelines for the management of chronic stable 
angina pectoris (ACC/AHA/ACP-ASIM, American College of Cardiology/American 
Heart Association/American College of Internal Medicine and American Medical 
Association).                 
4.2. Differentiation Standard of Traditional Chinese Medicine 
According to the prescription composition and function of Xinnaoning Capsule, 
and referring to the Guiding Principles for Clinical Research of Coronary Heart 
Disease and Angina Pectoris Treated with Chinese Medicine and Natural Medicine in 
2011, the syndrome differentiation and diagnosis criteria of Angina Pectoris with Qi 
stagnation and blood stasis syndrome were drawn up: 
Diagnostic criteria of chest arthralgia in traditional Chinese medicine 
    ①Chest pain, even chest pain thoroughly back chest pain, even chest pain 
thoroughly back； 
    ②The lighter ones only feel chest tightness, suffocation and 
breathlessness.； 
Qi stagnation and blood stasis syndrome： 
Main symptoms: chest pain, chest tightness 
Secondary symptoms: chest swelling, palpitation, shortness of breath, purple lips, 
fatigue, dizziness, dark purple veins at the bottom of the tongue, irritability. 
Tongue image: dark tongue. Pulse: astringent.             
One of the main symptoms, two of the secondary symptoms and supporters of 
tongue and vein can be diagnosed. 
 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
4. 3. Angina Pectoris Integral Scoring Method 
（Angina 
Pectoris） 
 
 
 
 
1. Frequency： 
0 
weekly 
1-3times per day or CCSⅡ                 
≥4times per day or CCSⅢ 
0 
2 
4 
6 
 
 
2. Duration： 
0 
Every pain lasting≤5min。                  
Every pain lasting＞5，and＜10min。            
Every pain lasting≥10min 
0 
1 
2 
 
 
 
3. Degree of 
pain： 
nothing 
The pain is not serious and does not affect daily life. 
The pain is severe and needs nitroglycerin.         
Severe seizures affect daily activities (such as 
dressing, defecation, etc.). 
0 
1 
2 
3 
 
4.Nitrogl
ycerin 
dosage 
nothing 
1-4tablets per week 
5-9tablets per week。 
≥10tablets per week 
0 
1 
2 
3 
 
4. 4. TCM Syndrome Integral Scoring Method                   
Mai-
n 
sym-
ptom 
Chest 
pain 
0：nothing 
2：The seizure is relieved by rest and does not affect daily 
life. 
4：Medication should be taken during seizures and normal 
activities can continue after remission. 
6：Frequent seizures affect daily activities (such as clothing, 
eating, walking, fecal symptoms) 
Chest 
tightness 
0：nothing 
2：Occasionally chest tightness can be alleviated by oneself 
4：Chest tightness attacks are frequent, but do not affect life 
and work  
6：Chest tightness continues to puzzle, affecting life and 
work 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Seco
ndar
y 
sym
ptom 
palpitatio
n 
0：nothing  
1：Occasional palpitation can be alleviated by itself 
2：Frequent episodes, but able to work persistently 
3：Palpitations persist, affecting life and work 
pant 
0：nothing 
1：Short breath after general activities  
2：Short breath after a little exercise 
3：Normally inactive and short of breath 
Chest and 
side      
fullness 
0：nothing 
1: Occasional distension and discomfort, short time, 
self-relief             
2: Depressed for a long time, occasionally need to take 
medicine.             
3: Recurrent seizures can only be alleviated by taking 
medicine. 
Mental 
exhaustio
n and 
fitigue 
0：nothing 
1: Mentally depressed, weak in strength teaching, can 
adhere to daily work and activities.             
2: Mental weakness, physical weakness, reluctant to stick to 
work             
3: Mental energy is so weak that it is difficult to stick to 
daily work. 
Purple 
lips 
0：no 
1：yes 
 dizziness 
0：no 
1:yes 
 
Sublingu
al 
venation 
0：Lavender 
1：Dark purple with bruises 
 
Impatient 
and 
irritable 
0：no 
1：yes 
Tongue 
manifestation 
Dark                     others _____              
Pulse 
condition 
uneven/ string-like pulse     others_____  
Note: Tongue and pulse are only described and not scored. 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
4. 5 Seattle Angina Questionnaire,SAQ。 
4.6 Participant selection criteria 
1) Referring to the Guidelines for the Diagnosis and Treatment of Chronic Stable 
Angina [6], issued by the Chinese Medical Association in 2007, the diagnosis of 
stable ischemic heart disease in 2012ACP/ACCF/AHA/AATS/PCNA/STS: 
Guidelines for Clinical Practice, and Guidelines for the Management of Stable 
Coronary Artery Disease in 2013 ESC, the diagnosis of coronary heart disease can be 
made in accordance with any of the following:             
(1) Has a clear history of old myocardial infarction, or PCI history, or bypass 
history;             
(2) Coronary angiography (results indicate that at least one coronary artery is 
stenosed and the lumen is stenosed more than 50%) or coronary CTA suggests that the 
lumen is stenosed more than 50%.             
2) Those who met the diagnostic criteria of chronic stable angina pectoris: those who 
had a history of angina pectoris more than 1 month and had no significant changes in 
the degree, frequency, nature and inducing factors of angina pectoris;             
3) The severity of angina pectoris of the Canadian Cardiovascular Society (CCS) was 
classified as Grade I-III, and the number of episodes per week was more than two.             
4) The syndrome differentiation of TCM is Qi stagnation and blood stasis syndrome.             
5) Age between 30 and 79 years old;             
6) Sign the informed consent. 
4.7 Subject exclusion criteria 
1) Severe cardiopulmonary insufficiency (grade III, IV, severe abnormal pulmonary 
function);             
2) Poor control of hypertension (systolic blood pressure (> 160 mmHg) or diastolic 
blood pressure (> 100 mmHg) after treatment;             
3) Severe primary diseases such as ALT, AST (> 1.5 times the upper limit of normal 
value) or Cr (> upper limit of normal value), hematopoietic system and so on.             
4) Acute myocardial infarction within 3 months after interventional therapy;             
5) Other factors affecting ST-T changes in ECG, such as myocardial hypertrophy, left 
bundle branch block, etc.             
6) Cardiac pacemaker;             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
7) Chest pain caused by other causes (moderate anemia, hyperthyroidism, etc.);             
8) Pregnancy, lactation or pregnancy planning;             
9) allergic constitution or allergic to known ingredients of research drugs;             
10) Those who participated in other clinical drug trials within one month;             
11) Researchers consider it inappropriate to participate in clinical research. 
4.8 Exfoliation excluded cases 
4.8.1 The withdrawal of the researcher's decision 
Subject withdrawal from the study refers to the decision to withdraw the case 
from the study according to the judgement of the researcher when the selected 
subjects are unsuitable for further study in the course of the study.                   
① In the study, patients with aggravated or aggravated conditions, such as 
increased number of angina attacks, prolonged duration of each attack or aggravated 
pain, must take emergency treatment measures such as adjusting treatment drugs, 
hospitalization or surgery； 
② In the study, some complications, complications or special physiological 
changes occurred in the subjects, and it was not appropriate to continue the study； 
③Prohibited drugs prescribed by the scheme were used in the study。 
④ In the study, if angina symptoms worsened in the subjects, those who were 
judged by the researchers to need to take other angina medicines or increase the 
dosage of drugs were withdrawn as invalid cases。 
4.8.2 Subjects withdraw spontaneously 
According to the informed consent, the subjects have the right to withdraw from 
the study halfway, or they have not explicitly proposed to withdraw from the study, 
but no longer accept medication and testing and lost interviews, which also belongs to 
"withdrawal" (or "fall off"). The reasons for their withdrawal should be understood 
and recorded as far as possible. Such as: poor self-efficacy; intolerable to some 
adverse reactions; unable to continue to accept clinical research; economic factors; or 
missing interviews without explaining the reasons.             
Whatever the reason, the case records should be kept for the withdrawal cases, 
and the final test results should be transferred to the final results. The efficacy and 
adverse reactions of the withdrawal cases should be analyzed by a full data set. All 
withdrawal cases should be filled in the case report form, the conclusion form and the 
reasons for withdrawal. In general, there are six kinds, namely, adverse events 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
(including adverse drug reactions and allergic reactions), lack of efficacy 
(deterioration or complications), violation of research programs, loss of interviews 
(including withdrawal of the subjects themselves), suspension of the applicant and 
others. 
4.8.3 Criteria for excluding cases 
① Misdiagnosis and wrong acceptance； 
② No post-medication record； 
③ No medication at all。 
4.9 Conditions for discontinuation of research 
Research discontinuation means that clinical studies have not been completed as 
planned and all studies have been stopped halfway. The main purpose of the 
suspension of research is to protect the rights and interests of subjects, ensure the 
quality of research and avoid unnecessary economic losses.             
(1) Serious safety problems occur in the study, and the study should be 
discontinued in time.             
(2) The study found that the effect of drug treatment is too poor, even ineffective, 
and has no clinical value. The study should be discontinued, on the one hand, to avoid 
delaying the effective treatment of subjects, while avoiding unnecessary economic 
losses.             
(3) It is difficult to evaluate the drug effect because of the major mistakes in the 
clinical research program. Or a well-designed program has significant deviations in its 
implementation, and it is difficult to evaluate the drug effect if it continues.             
(4) The applicant requests suspension (e.g. financial reasons, management 
reasons, etc.).             
(5) Drug administration departments should withdraw research, etc. 
5. Dosage regimen 
5.1  Administration method 
The course of treatment was 14 weeks, including 2 weeks of introduction and 12 
weeks of double blind treatment.             
Introducing period: 2 weeks, time window (+2 days).             
Introducing drug regimen: Both groups were given Xinnaoning capsule 
Simulator 3 capsules per time, 3 times per day, orally, after meals.             
Course of treatment: 12 weeks, time window (+4 days).             
Drug regimen for treatment period:             
Test group: Xinnaoning capsule 3 capsules per time, 3 times per day, oral, after 
meals.             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Control group: Xinnaoning capsule Simulator 3 tablets per time, 3 times per day, 
oral, after meals.             
Basic treatment: During the introduction and treatment period, the experimental 
group and the control group could use antiplatelet drugs, angiotensin converting 
enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (ARB), statins 
lipid-lowering drugs, calcium antagonists, beta-blockers, long-acting nitrates and 
other drugs without changing the original dosage. Nitroglycerin 0.5 mg can be 
administered sublingually, and the times and dosage of medication can be recorded in 
detail.             
Sports regulations: 3-5 times a week, each lasting 30-40 minutes, 6.5-7.5 
kilometers a week. See Annex 1 for details. 
5.2 Pharmaceutical Information for Testing Drugs 
(1) Introducing drugs: Xinnaoning capsule simulator, the production unit is 
Guizhou Jingcheng Pharmaceutical Co., Ltd. Specification: 0.45g for each tablet, 12 
tablets for each board, batch number: 20171113 valid until August 2019.             
(2) The experimental group drug: Xinnaoning Capsule, the production unit is 
Guizhou Jingcheng Pharmaceutical Co., Ltd. Specification: 0.45g for each tablet, 12 
tablets for each board, drug batch number 20170916. It is valid until August 2019.             
(3) Control group drug: Xinnaoning capsule simulator, the production unit is 
Guizhou Jingcheng Pharmaceutical Co., Ltd. Specification: 0.45g for each tablet, 12 
tablets for each board, drug batch number: 20171113. It is valid until August 2019. 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
5.3 Pharmaceutical Packaging for Testing Drugs 
There are corresponding drug numbers and labels attached to the test drugs. The 
test drugs and the control drugs are packed in the same package. Each large package 
contains three boxes. The package contains Xinnaoning capsule or Xinnaoning 
capsule placebo. Each package contains 28 + 4 days of dosage. The drug was packed 
independently during the introduction period, and the dosage of 14 + 2 days was 
included in the package. The contents of the label include batch approval number, 
drug number, drug name, function, taking method, storage condition, drug supplier, 
etc., and the words "for clinical research only". 
5.4 Case allocation method 
Randomization method was adopted, which was carried out according to the 
center. With the help of SAS 9.1.3 statistical software, the random arrangement (i.e. 
random coding table) of the treatment (test drug and control drug) received by 240 
subjects was generated. According to the randomly determined drug number allocated 
by each hospital, each center allocates continuously coded drugs connected with each 
other. Random numbers are sealed in opaque envelopes and centralized managed by 
test centers.             
Each center screens patients, and qualified persons are selected. Drug 
administrators distribute drugs one by one according to the order of each subject's 
visiting and drug number from small to large. Subjects were asked to take the remnant 
drugs back when prescribed visiting points were prescribed. Drug administrators 
should fill in the "test drug distribution and recovery record form" in time. 
5.5 Dose selection and administration time 
In this experiment, all subjects were given a uniform fixed dose, which remained 
unchanged during the experiment, i.e. during the experiment, the dosage should not be 
adjusted or the mode of administration should not be changed. If the adverse events 
necessarily changed or other reasons caused changes, detailed records and treatment 
according to excluded cases were made. 
5.6 Blind method 
A double blind design was used in this study.             
(1) Generation of processing codes             
Randomization method was used. They are carried out according to the center. 
With the help of SAS 9.1.3 statistical software, the random arrangement (i.e. random 
coding table) of the treatment (test drug and control drug) received by 240 subjects 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
was generated.             
(2) Drug preparation             
Firstly, random sampling of the drugs prepared by the applicant (test drugs and 
control drugs) is conducted to provide the corresponding drug inspection report. 
Secondly, the bidders will package the drugs according to the requirements of drug 
packaging.             
(3) Preparing for Emergency Letters             
1) Emergency letters, drug numbers and blindness regulations of Xinnaoning 
Capsule in the clinical study of chronic stable angina pectoris are printed on the sealed 
opaque envelope. If it is disassembled, it is necessary to specify the disassembler, the 
date of disassembly, the reason and so on, and record it in the case report form.              
2) The envelope contains the information of the patient's medication and the 
address of the unit and the address that should be reported immediately. After the 
preparation of the emergency letter, it will be sent to the centers along with the drugs, 
which will be recovered after the study.             
(4) Packaging and numbering of drugs according to processing codes            
Personnel unrelated to clinical observation, surveillance and statistical analysis of this 
clinical study will attach the corresponding drug number to the conspicuous position 
of the external packaging of the drug according to the established processing code.             
(5) Processing Blind Records of Coding and Drug Packing             
The whole drug coding process is written into a document form by the blind 
person, that is, a blind record, which is kept as one of the documents of the clinical 
research. Its contents include: preparation of bidders'medicines, packaging, usage, 
storage requirements, methods of drug distribution, generation of random processing 
codes, packaging of medicines according to each subject, emergency letters, 
inspection reports of test drugs and control drugs, preservation of blind bases, 
provisions for eliminating blindness and distribution of the number of medicines in 
each center, etc.             
(6) Distribution of packaged drugs             
Emergency letters with separate packages of research drugs and corresponding 
drug numbers are sent to the research centers according to random central numbers.             
(7) Blind bottom preservation             
All the blind bases formed by coding, together with the initial values of random 
numbers and the length of blocks, are sealed and handed over to the drug clinical 
research institutes and bidders of Xiyuan Hospital, Chinese Academy of Medical 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Sciences, respectively, for proper preservation. During the research period, the blind 
bases are not to be dismantled. The study will be considered invalid if any 
non-prescribed blind bottom leak occurs and affects the objectivity of the results of 
the study.             
(8) Blind Audit and Disclosure Provisions             
Blind auditing refers to checking and evaluating the data of the database after the 
last medical record report form is input into the database until the first blindness is 
uncovered.             
When all the case reports are entered in two copies and checked correctly, the 
data manager writes out the database inspection report, which includes the completion 
of the study (including the list of dropped subjects), selection/exclusion criteria, 
integrity check, logical consistency check, outlier data check, time window check, 
combined drug use check, adverse event check and so on.             
At the blind auditing meeting, the main researchers, bidders, supervisors, data 
managers and biostatistics professionals will examine the subjects'signing of informed 
consent, the situation of maintaining the blindness in the research process and the 
emergency situation of eliminating the blindness in the research process, and make 
decisions on the issues raised in the database inspection report, and write the blind 
auditing report. The database will be locked at the same time.             
After data locking, the first blindness was uncovered by the staff who kept the 
blind bottom. This blindness uncovering only listed the group code of each subject 
(such as the experimental group or the control group). It was input to the computer by 
the statistic analyst and linked to the data file for statistical analysis. When the 
statistical analysis is finished, the statistical analysis report is written. At the summary 
meeting, the second blindness was uncovered. This blindness uncovering marked the 
actual corresponding groups of A and control group (such as experimental group or 
control group).             
(9) Regulations on Emergency Disclosure of Blindness             
When an emergency (such as a serious adverse event) occurs or the patient needs 
to know what kind of treatment the patient receives, the researcher immediately 
notifies the main researcher, urgently opens the emergency letter, and promptly 
notifies the head of the base and the inspector of the unit. Once the emergency letter is 
opened, the numbered subjects will withdraw from the study. Researchers should 
record the causes in the case report form, and record the time, place and cause of 
emergency blindness on the emergency letter. At least two people should sign it. At 
the end of the study, the case report forms were retrieved together for blind review 
after the study.             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
(10) Failure of double-blind study stipulates that the rate of blind bottom leak or 
emergency letter open exceeds 20%. 
5.7 Drug Distribution and Preservation 
Drug administrators (centers, according to their own management system, set up 
a special person responsible for the preservation, distribution, recovery, recording and 
return or recovery of experimental drugs) distribute drugs according to the order of 
the selected time and the number of drugs from small to large, and then withdraw the 
surplus experimental drugs after stopping the drugs, and fill in the Test Drug Use 
Record Form in time, which includes: The date of drug release, the name of the 
subject, the quantity of drug delivery, the date of drug recovery, the quantity of drug 
recovery, the signature of the dispenser and the signature of the drug collector, etc. 
After the completion of all trials, the drug administrator is responsible for returning 
the remaining drugs to the applicant or destroying them according to the procedure 
(filling in the "Test Drug Return/Destruction Certificate") and submitting them to the 
clinical trial unit for archiving.             
During the test period, a management system should be established for the trial 
period of the test drugs, and special cabinets should be set up to keep the test drugs 
and store them in places where ventilation, drying and temperature are suitable. The 
drug administrator shall carry out unified management. 
5.8 Drug counting and drug compliance judgment of subjects 
During each follow-up visit, the observer should check the remaining empty 
boxes of the subjects, ask whether they take the drugs on time and in quantity, 
whether they are missing, missing or undertaking, and record them in the case report 
form in time for judging the compliance of clinical medication.             
In the course of clinical trials, the compliance of subjects is mainly prescribed 
medication. The subjects should be strictly prescribed medication to avoid 
self-imposed other treatment methods.             
Compliance of test medication=(dosage-not-dosage)/dosage x l00% 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
5.9 Regulations on combined use of drugs 
1. In addition to experimental medication, nitroglycerin tablets can be used to 
alleviate symptoms when angina attacks. For drugs already used to treat coronary 
heart disease before inclusion, such as antiplatelet drugs, angiotensin-converting 
enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (ARB), statins, 
calcium antagonists, beta-blockers and long-acting nitrates, the original varieties and 
dosages can be continued without adjustment. During the study period, it is forbidden 
to add any other Chinese and Western medicines which have therapeutic effects on 
angina pectoris of coronary heart disease.             
2. For the original and emerging diseases requiring drug treatment, the drug 
combination should be recorded in the medical record and CRF in detail, including 
the generic name of the drug, dosage and method of administration, the starting time 
of drug use and the reasons for its use.  
6. Observation items 
6.1 General record items 
Drug number, center code, subject name, start date, etc. 
6.2 Observation index 
6.2.1 General observation indicators 
1) Demographic characteristics: gender, age, height, weight, etc.             
2) Medical history, course of disease, treatment history, allergic history, complications 
and medication, etc.             
3) Other screening indicators: urinary pregnancy test (women of childbearing age).  
6.2.2 Effectiveness indicators 
Main effective indicators: the efficacy of angina symptoms.             
Secondary effectiveness indicators:             
(1) Curative effect of TCM syndromes;             
(2) Grading changes of severity of angina pectoris;             
(3) Changes in the number of angina attacks per week;             
(4) Nitroglycerin dosage;             
(5)Seattle Angina Scale score;             
(6)Blood HCY: The changes of blood HCY before and after treatment were compared 
between the two groups.             
（7）Incidence of cardiovascular events (sudden cardiac death, acute myocardial 
infarction, heart failure, percutaneous transluminal coronary angioplasty, coronary 
artery bypass grafting, malignant arrhythmia, cardiogenic cerebrovascular accident, 
angina pectoris requiring hospitalization, etc.). 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
6.2.3 Safety indicators 
(1) adverse event             
(2) vital signs: (blood pressure, body temperature, breathing and heart rate after 10 
minutes'rest);             
(3) Routine safety laboratory examinations: blood routine (RBC, WBC, HGB, PLT), 
urine routine (ERY, LEU, PRO), stool routine (containing occult blood), liver function 
(ALT, AST, ALP, TBIL, GGT), renal function (BUN, Cr), coagulation (PT, APTT, FIB, 
TT)  
6.2.4 Other observational indicators 
(1) Fasting blood glucose: The changes of fasting blood glucose before and after 
treatment were compared between the two groups.             
(2) Four items of blood lipid: The changes of four items of blood lipid before and 
after treatment were compared between the two groups.  
6.3 Observation window 
12 weeks ±4 days. 
6.4 Test procedure 
6.4.1 Visit 1-Import Period (-14±2 days) 
 Obtain written informed consent             
 Verification of selection/exclusion criteria for the import period             
 Access to demographic information             
 Obtain medical history, including concomitant medication             
 Conduct a comprehensive physical examination             
 Record concomitant medication             
 Issuance of medication and diary cards during the introduction period             
 ECG examination             
 Record nitroglycerin dosage 
6.4.2 Visit 2 - before treatment (0 days) 
 Verification of selection/exclusion criteria             
 TCM Symptom Score             
 General information, main related symptoms and signs             
 Record concomitant medication             
 Subsequently, the experimental drugs were distributed in groups, and the 
remaining drugs were recovered and recorded.             
 Physicochemical examination: blood routine, urine routine, stool routine + 
Occult blood, electrocardiogram, liver function (ALT, AST, ALP, GGT, 
TBIL), renal function (BUN, Cr), four items of coagulation, blood HCY, 
fasting blood sugar and blood lipid             
 Major related symptoms and signs             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
 Seattle Angina Questionnaire             
 Grading changes of severity of angina pectoris;             
 Record nitroglycerin dosage             
 Record adverse events 
6.4.3 Visit 3 (4 weeks ± 4 days) 
 Fill in the syndrome integral form             
 Major related symptoms and signs             
 Seattle Angina Questionnaire             
 Grading changes of severity of angina pectoris;             
 Record concomitant medication             
 Record adverse events             
 Recovery of surplus drugs and distribution of experimental drugs             
 Record nitroglycerin dosage             
 Evaluation of curative effect 
6.4.4 Visit 4 (8 weeks ±4 days)） 
 Fill in the syndrome integral form             
 Major related symptoms and signs             
 Seattle Angina Questionnaire             
 Grading changes of severity of angina pectoris;             
 Confirmation of the subjects'return of unused research drugs             
 Record concomitant medication             
 Record adverse events             
 Record the dosage of nitroglycerin             
 Evaluation of curative effect 
6.4.4 Visit 5 (12 weeks ± 4 days) 
 Fill in the syndrome integral form             
 Major related symptoms and signs             
 Seattle Angina Questionnaire             
 Grading changes of severity of angina pectoris;             
 To confirm that the subjects returned untreated research drugs;             
 Record concomitant medication            
 Record adverse events             
 ECG examination             
 Physicochemical examination: blood routine, urine routine, stool routine + 
Occult blood, electrocardiogram, liver function (ALT, AST, ALP, GGT, 
TBIL), renal function (BUN, Cr), four items of coagulation, blood HCY, 
fasting blood sugar and blood lipid             
 Record the dosage of nitroglycerin             
 Evaluation of curative effect 
 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
7. Observation of adverse events 
7.1 Recording of adverse events 
In the research case history and case report form, "adverse event record form" is 
set up, which requires researchers to fill in the occurrence time, severity, duration, 
measures taken and outcome of adverse events truthfully. The relationship between 
adverse events and experimental drugs was also judged. 
7.1.1 Definition of Adverse Event (AE) 
It refers to adverse medical events that occur during a clinical trial when a 
subject receives a drug, but it does not necessarily have a causal relationship with the 
treatment. Specifically, it includes the following: suspicious adverse drug reactions, 
such as central nervous system, digestive system, hematopoietic system, rash, pruritus 
and other toxic and side effects; all reactions due to drug overdose, abuse, withdrawal, 
allergy or toxicity; apparently unrelated diseases, including the aggravation of 
pre-existing diseases; abnormal biochemical indicators of liver and kidney function. 
Abnormalities found by physical examination or physical examination and requiring 
clinical treatment or further examination (unlike repeated validation tests), etc. 
Abnormalities found in laboratory tests require clinical treatment or further 
investigation (unlike repetitive validation tests). If these abnormalities are related to 
reported events (e.g. elevated transaminase levels in jaundiced subjects), they should 
be described in the notes to the clinical event report and not included as a separate 
adverse event. 
7.1.2 Judgment of Causality between Adverse Events and Testing Drugs 
In the event of adverse events, the researcher decides the diagnosis and treatment 
measures based on the condition of the patient and whether to discontinue the 
observation. In case of serious adverse events, the unit undertaking clinical research 
should take necessary measures immediately to protect the safety of the subjects. If 
the duration of the trial is more than 4 weeks, the subjects will quit because of the 
aggravation of the illness (increased number of attacks, prolonged duration of attacks, 
increased degree of pain, increased dosage of nitroglycerin or increased level of 
attacks). Such cases need to be included in PPS statistics as non-curative cases. 
Researchers should record the relevant information in detail on the medical records of 
scientific research.             
Criteria for grading the severity of adverse events             
Mild: Usually temporary and does not affect normal daily activities.             
Moderate: quite uncomfortable, can affect normal daily activities.             
Severity: unable to carry out normal daily activities.             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Judgment of causality with drugs:             
1) Causal judgment indicators of adverse reactions:             
Item 1: Whether there is a reasonable relationship between the time of starting 
medication and the time of suspicious occurrence;             
Item 2: Does the suspicious adverse reactions conform to the known types of 
adverse reactions of the drug?             
Item 3: Whether the suspected adverse reactions can be explained by the patient's 
pathological condition, combination of medication, therapy or previous therapy;             
Item 4: Does the suspicious adverse reaction decrease or disappear after 
withdrawal or dose reduction?             
Item 5: Does the same reaction reappear after the suspicious drug is used again?             
Causality criteria: according to the above five judgment indicators to determine 
the order. 
Causal Judgment of Adverse Reactions 
Result 
Judgement index 
item1 
item 2 
item 3 
item 4 
item 5 
Definitely 
related 
+ 
+ 
－ 
+ 
+ 
Vey kikely 
related 
+ 
+ 
－ 
+ 
？ 
Probably 
related 
+ 
+ 
± 
± 
？ 
May be 
irrelevant 
+ 
－ 
± 
± 
？ 
Impossibly 
related 
+ 
－ 
+ 
－ 
－ 
Explanation：＋yes、－no、±not sure、？unknown。 
2) Based on the above table, the relationship between the following five levels of 
adverse events and drugs was determined. 
①Definitely related；②Vey kikely related；③Probably related；④May be 
irrelevant；⑤Impossibly related。 
The total number of cases with 1+2+3 was used as the molecule to calculate the 
incidence of adverse reactions, and all the selected cases for adverse reactions 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
evaluation were used as denominators. 
7.1.3 Recording and reporting of adverse events 
Researchers should explain to the subjects that they should truthfully reflect the 
changes of their condition after medication, but avoid induced questions. While 
observing the curative effect, we should pay close attention to adverse events or 
unexpected side effects (including symptoms, signs, laboratory tests), analyze the 
causes, make judgments, and follow up observation and record.             
For adverse events during the trial, the researchers should record the occurrence 
time, symptoms, degree, duration, treatment measures and outcome in the case report 
form, judge the correlation between the adverse events and the test drugs, sign and 
date them. 
7.1.4 Treatment of subjects with adverse events 
When adverse events occur, researchers can decide on the measures to be taken 
according to their condition. Generally, the following methods are adopted:  
(1) observation without discontinuing the drug test; 
(2) observation and discontinuation of the drug test without remedial treatment;  
(3) discontinuation of the drug test with remedial treatment.             
All adverse events should be tracked and investigated, and the treatment process 
and results should be recorded in detail until the subjects are properly resolved or the 
condition is stable. Those with abnormal laboratory indicators should be tracked back 
to normal or pre-medication level. According to the severity of adverse events, 
follow-up methods can be used to select hospitalization, outpatient service, home 
visits, telephone and other forms. 
7.2 Dealing with Serious Adverse Events 
7.2.1 Definition of Serious Adverse Event 
Serious adverse events refer to the following adverse events occurring at any 
dose of the test drug or at any time during the observation period, including the need 
for hospitalization, prolonged hospitalization time, disability, impairment of working 
ability, life-threatening or death-threatening events. 
7.2.2 Treatment and Report of Serious Adverse Events 
If serious adverse events occur in the trial, the unit undertaking the clinical trial 
shall take necessary measures immediately to protect the safety of the subjects, and 
report to the local provincial drug supervision and administration department, the 
State Food and Drug Administration, the applicant and the ethical committee of the 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
unit responsible for the clinical trial within 24 hours, and notify the experimental units. 
The applicant will ensure that the reporting procedure meets all legal and regulatory 
requirements. 
Table 7.2.2 Contacts for reporting serious adverse events 
Organization 
Contacts 
Telephone 
Fax 
Ethics Committee of Xiyuan Hospital, Chinese 
Academy of Traditional Chinese Medicine 
Mingjie 
Zi 
010—62835646 
010-62835646 
Guizhou Jingcheng Pharmaceutical Co., Ltd. 
Minghu
an Luo 
13891950813 
010-58462594 
Beijing Duheng for Drug Evaluation and 
Research Co., Ltd. (DDER) 
Chunshe
ng Qiao 
010-58462584 
010-65735819 
CFDA Drug and Cosmetics Registration and 
Administration Department, Drug Research and 
Supervision Department 
----- 
010-88863120 
010-88363228 
7.2.3 Recording of serious adverse events 
Researchers must fill in the "Serious Adverse Events Report Form", record the 
occurrence time, duration, measures taken and outcome of serious adverse events, and 
sign and date the report.  
7.3 Disassembly and Processing of Emergency Letters 
Emergency letters are called emergency blindness cracking only when the 
subject has serious adverse events and needs to identify the types of drugs used 
immediately. Once blindness is broken, the subject will be discontinued and treated as 
an exfoliated case. At the same time, the results will be notified to the unit responsible 
for the test, the bidder and the inspector. Researchers should record the reasons for 
breaking the blindness, date it and sign it in the case report form.  
7.4 Follow-up of unremitted adverse events 
All adverse events that have not been completely alleviated at the end of the 
course of treatment should be tracked and observed to be properly resolved or stable.  
8. Evaluation of clinical trials 
8.1 Evaluation of clinical effectiveness 
Referring to the Guiding Principles of Clinical Research Technology of 
Traditional Chinese Medicine and Natural Medicine for Coronary Heart Disease and 
Angina Pectoris. 
8.1.1 Criteria for evaluation of main therapeutic indicators 
The curative effect of angina pectoris symptoms: According to the method of 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
angina symptom integral, the scores of angina pectoris symptoms before and after the 
two groups were compared: 
 Significant effect: n (> 70%);             
 Effective: n (>30%) and (< 70%);             
 Invalid: n < 0, n < 30%;             
 Aggravation: n < 0.效：n≥70%； 
8.1.2 Evaluation criteria of secondary efficacy indicators 
1) The curative effect of TCM syndrome scoring:             
Relevant statistical methods were used to analyze the score reduction value and 
50% score reduction rate of the two groups.             
2) Grading changes of severity of angina pectoris: Comparing the severity 
grading of CCS angina pectoris between the two groups before and after 
treatment, and evaluating the therapeutic effect of drugs on chronic stable angina 
pectoris.             
3) The change of angina pectoris attack times per week: The change of angina 
pectoris attack times per week before and after treatment was compared between 
the two groups.             
4) Nitroglycerin consumption: The corresponding statistical methods were used 
to analyze the consumption of nitroglycerin before and after treatment in the two 
groups.             
5)SAQ: Compare the changes of each dimension of the Seattle Angina Scale 
before and after the treatment of the two groups, and evaluate the effects of drugs 
on the body function and quality of life of the subjects.             
6) Change of HCY: Compare the changes of HCY before and after treatment in 
the two groups, and evaluate the effect of drugs on reducing the incidence of 
heart disease.             
7) Incidence of cardiovascular events (sudden cardiac death, acute myocardial 
infarction, heart failure, percutaneous transluminal coronary angioplasty, 
coronary artery bypass grafting, malignant arrhythmia, cardiogenic 
cerebrovascular accident, angina pectoris requiring hospitalization, etc.).心血管
事件发生率(心源性猝死、急性心肌梗死、心力衰竭、经皮冠状 动脉腔内血
管成形术、冠状动脉搭桥术、恶性心律失常、心源性脑血管意外、需要住院
治疗的心绞痛等)。 
8.2 Clinical safety evaluation 
1. Possible adverse reaction symptoms.             
2. General physical examination items, such as body temperature, pulse, 
breathing, blood pressure, etc.             
3. Laboratory examination: blood routine, urine routine, stool routine + Occult 
blood, electrocardiogram, liver function (ALT, AST, ALP, GGT, TBIL), renal function 
(BUN, Cr), coagulation, fasting blood sugar, blood lipid. 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
 9. data management 
(1) Fill-in and transfer of case report form (CRF)             
The completed case report forms are reviewed by clinical researchers and 
monitors, and then submitted to the data statistical units for data entry and 
management. All processes need to be documented.             
(2) Data input and modification             
Data entry and management reasons are the responsibility of data managers in 
statistical units. Two data managers independently enter and proofread two copies.            
Questions on the case report form. Data managers will fill in the Question Answer 
Form (DRO) and send inquiries to researchers through clinical monitors. Researchers 
should answer and return the questions as soon as possible. Data managers modify the 
data according to the researchers'answers, confirm and input them, and then issue 
DRO again if necessary.             
(3) Locking of database             
After blindly checking and confirming the correctness of the database, the main 
researchers, bidders and statisticians lock the database. If the problem is found after 
database locking, it can be corrected in the process of statistical analysis after 
confirmation, and recorded and explained.            
(4) blindness elimination             
After all the research data are checked and locked, the first blindness detection is 
carried out, and then the statistical analysis is carried out according to the statistical 
plan, the statistical analysis report is written, and finally the second blindness 
detection is carried out. 
10. statistical analysis 
10.1 Analytical Data Set 
(1) Full Analysis Set (FAS): refers to the ideal set of subjects as close as 
possible to the principle of intentional analysis. The data set is derived from all 
randomized participants by eliminating the participants with the least and reasonable 
method.             
(2) PPS: It is a subset of the total analysis set. These subjects are more 
compliant with the scheme. Compliance includes the following considerations, such 
as the treatment they received, the absence of major efficacy indicators, and the 
absence of major violations of the research scheme.             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
(3) Safety Data Set (SS): When evaluating safety and tolerance, the set of 
subjects used to aggregate is called Safety Data Set. Subjects who received at least 
one treatment after randomization were included in the safety analysis set. 
10.2 Statistical analysis method 
10.2.1 Statistical description 
(1) whether it conforms to normal distribution: modifying statistical methods or 
transforming data when it does not conform;             
(2) Whether there is outlier value or not: make statistical and professional 
analysis to decide whether to choose or not;             
(3) Processing the missing value of the main therapeutic index data: When the 
main therapeutic effect data of individual subjects are missing, the way to fill the 
missing data is determined from the statistical and professional point of view. For 
missing cases, the data were transferred from the previous measurements; for missing 
data, the measurements were made only once, and the mean of all the data was used to 
fill in the missing data.             
(4) The proportion of exfoliated cases: generally not more than 20%, otherwise 
it should be analyzed and explained;             
(5) Descriptive statistical analysis: calculating mean, standard deviation, 
confidence interval, maximum, minimum, median, frequency (constituent ratio), etc.  
10.2.2 Statistical expression 
(1) The report is mainly expressed in tables, which are self-evident, i.e. with 
headings, annotations and examples.             
(2) The results of repeated measurements can be expressed in tables or statistical 
charts to increase readability.             
(3) Bilateral tests are used in statistical tests. Those whose P is less than or equal 
to 0.05 will be considered as having statistical significance.  
10.2.3 Statistical analysis content 
(1) CDAS3.0 statistical software will be used for statistical analysis.             
(2) The main therapeutic data set was FAS analysis population, and the 
therapeutic PPS population was also analyzed.             
(3) Except for the superiority test of the main therapeutic indicators, all other 
statistical tests are carried out by bilateral test, and the difference of P value less than 
or equal to 0.05 will be considered statistically significant.             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
(4) The measurements of each visit in different treatment groups will be 
described by means of standard deviation. Compared with the baseline values at the 
time of admission, paired t-test was used to compare the differences between before 
and after admission. Variance analysis was used to compare the changes before and 
after treatment in each group.             
(5) Frequency (constituent ratio) was used to describe the counting data of each 
visit in different treatment groups. 2 test or non-parametric test were used to test the 
changes before and after treatment in each group.             
(6) Comparability analysis: Comparing demographic data and other basic value 
indicators to measure the comparability between the two groups.             
(7) Compliance analysis: Compare the two groups of patients whether to use the 
research drugs on time and in quantity, not using the drugs prohibited in the program.             
(8) Abscission analysis: _2 test will be used to compare the total abscission rate 
and the abscission rate due to adverse events in each group.             
(9) Equilibrium analysis of basic values: using variance analysis or 2 test to 
compare demographic data and other basic value indicators to measure the two groups 
of equilibrium.             
(10) Effectiveness analysis: PPS and FAS were used to analyze the main 
indicators and global indicators, and CMH test considering the central effect was used 
to analyze the efficacy of the two groups. The main effect indicators were selected to 
treat 12 weeks of angina symptoms, and the placebo was used as the control for 
statistical test.             
(11) Analysis of factors affecting efficacy: If there are significant correlative 
factors affecting efficacy, these factors should be considered as covariance analysis or 
logistic regression analysis when comparing the efficacy of the two groups. Detailed 
list of combined medication is required.             
(12) Safety analysis: 2 test was used to compare the incidence of adverse events 
in the two groups, and list the adverse events in the study; analysis of the 
normal/abnormal changes of laboratory results before and after the study and the 
relationship between abnormal changes and research drugs. 
11. Quality Control and Guarantee of Clinical Trials 
11.1 Records of clinical trials 
Researchers should fill in all cases according to the design requirements of the 
"case report form" one by one. Research medical records and case report forms shall 
be used as original records and shall not be changed. When making any corrections, 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
the original record shall not be blackened. Only a horizontal line can be drawn at the 
amendment and the reasons can be explained by adding a description. The physician 
participating in the clinical trial shall sign and date it.             
Laboratory data in clinical trials should be recorded, and original reports (or 
copies) should be glued to the medical records of the study. Data that are significantly 
higher or beyond clinical acceptability should be verified and explained by the 
physician participating in the clinical trial.             
All medical records and case reports should be filled in with black or blue-black 
signature pens. Ball pens, pens or pencils are prohibited. 
11.2 Management of experimental drug use 
All drugs should be kept in the scientific pharmacy of the hospital and 
designated special persons to be responsible for the preservation, distribution, 
recovery and return of the drugs. For the cases of withdrawal and missing visits, the 
experimental drugs should be recovered. At the same time, we should establish the 
Record of Use of Drugs in Clinical Trials, which includes the date of issuance of 
drugs, the names of subjects, the number of drugs issued, the date of recovery, the 
number of drugs recovered, the signature of the dispenser and the signature of the 
drug collector.  
11.3 Training Researchers 
Before the start of clinical trials, the personnel participating in clinical trials 
should be trained in a unified way so that researchers can fully understand the specific 
connotations of the clinical trial program and its indicators; the quantification criteria 
of symptoms and signs are basically the same; the description of conscious symptoms 
should be objective, and should not be induced or prompted; and the prescribed 
objective indicators should be carried out according to the time points and methods 
prescribed by the program. Check; Familiar with the recording methods of case 
history and CRF; pay attention to observe adverse reactions or unexpected side effects, 
and follow up observation. 
11.4 Measures to Improve Observation Consistency 
1) Qualification examination of researchers participating in clinical trials: They 
must have the professional expertise, qualification and ability of clinical trials. After 
qualification examination, they are determined and the personnel requirements are 
relatively fixed.             
2) Researchers should verify significant deviations or data beyond acceptable 
limits and make necessary explanations by the researcher.             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
3) Each test item must indicate the unit of measurement used.             
4) Each clinical research unit should appoint a special person to regularly check 
the progress of clinical trials and carefully verify the data and records.             
5) If necessary, the bidding unit will organize a mid-term clinical meeting to 
check the previous work, analyze the problems found in the clinical trial process and 
put forward the rectification.  
11.5 Laboratory Quality Control Requirements 
Standard operating procedures and quality control procedures should be 
established in laboratories. When the main indicators may be subjectively affected, a 
consistency test is needed.             
Each testing unit shall provide "normal range of laboratory inspection" for its 
own unit. If there is any change in the test, additional explanation should be provided 
in time. Effective measures should be taken to correct the differences in the results of 
laboratory tests or the range of normal reference values.  
11.6 Surveillance of clinical trials 
Qualified inspectors appointed by the applicants will regularly visit the test 
centers during the trial period to ensure that the rights and interests of the subjects in 
the clinical trials are guaranteed, that the data recorded and reported in the trials are 
accurate and complete, and that the trials follow the approved programs, drug clinical 
trial management norms and relevant regulations.             
The inspector is required to have direct access to source documents (original 
documents, data and records). Direct contact includes allowing examination, analysis, 
and verification of important records and reports for any evaluation of clinical trials.             
Researchers should be able to contact the Ombudsman by telephone at any time 
for discussion.  
12. Ethical principles 
Before the clinical trial is officially started, it must be discussed, revised and 
signed by the researcher and the applicant (i.e. this scheme), which can be submitted 
to the Ethics Committee for approval before the trial can be started. If problems arise 
in the actual implementation of clinical trials and need to be revised, please submit to 
the applicants that, after consultation and discussion by the multi-center coordinating 
committee, the responsible unit of clinical trials should revise the scheme and submit 
it it in writing to the applicants and the experimental units for signature and approval, 
and then to the Ethics Committee for approval; if it is found that the drug used in the 
trial is involved, it should be carried out after approval by the ethics committee. 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Important new material must be revised in writing and sent to the Ethics Committee 
for approval, and the subject's consent will be obtained again.             
Before the start of a clinical trial, researchers must provide the subjects with 
detailed information about the nature of the trial, the purpose of the trial, the potential 
benefits and risks, alternative therapies available, and the rights and obligations of the 
subjects in line with the Helsinki Declaration, so that the subjects can fully understand 
and consent and sign the informed consent. Bed test. Every subject should leave 
detailed contact address, telephone, identity certificate and other information. At the 
same time, the doctor should leave his own contact telephone to the subject so that the 
subject can find the doctor whenever the condition changes. This is also conducive to 
the doctor to keep abreast of the change of the condition, reminding the subject to 
return to the doctor in time to avoid missing the visit. 
13. Data preservation 
Researchers must keep the original data of each subject, including all medical 
records and visiting records (including demographic and medical information, 
laboratory data, electrocardiogram, other examination or evaluation results), and a 
signed consent form.             
Case report forms are written in carbon-free duplicate triple format. After data 
entry is completed, the applicants, clinical trial units and responsible units of clinical 
trials are filed separately.             
All test data must be kept for 5 years after the end of the test. If required by 
existing regulations or agreements with bidders, such information should be kept for a 
longer period of time. The applicant or his agent will notify the researcher in writing 
of the deadline when the information no longer needs to be kept. If the research unit 
adjusts the location of the documents, the researcher shall notify the applicant or his 
agent in writing.  
14. Modification of the scheme 
After approval by the ethics committee, if there are significant changes in the 
implementation process, the main researchers in charge of clinical trials will write the 
"revised instructions" and sign them. At the same time, they need to report to the 
Ethics Committee for approval before they can be implemented. If no principled 
modification is made, the principal investigators, statisticians and bidders of the 
responsible unit of clinical trial shall discuss and decide together, and notify other 
participating units. 
15. Organization and Management of Tests 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
15.1 Progress and Arrangement of Test Work 
This pilot project will submit an application for ethical review in November 2017.             
It is planned to start clinical trials in January 2018.             
All cases are scheduled to be enrolled in November 2018.             
All cases are scheduled to be completed in January 2019.             
It is planned that all CRF checks and collections will be completed in February 2019, 
and data entry and data answering will be completed.             
The statistical report is scheduled to be completed in April 2019.             
The final report is scheduled to be completed in May 2019.             
All clinical trials are planned to be completed within 18 months after the trial costs 
and drugs are in place.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Signature Page for Participating Center Researchers 
1. I have obtained and reviewed the researcher's Manual of Xinnaoning Capsule 
Project.             
2. I have read the test plan and consider it ethical.             
3. I agree to carry out this test in accordance with all applicable regulations and 
guidelines.             
4. I agree to maintain the confidentiality of all information obtained or related to 
this scheme.             
5. I agree that all electronic signatures will be equally handwritten and legally 
binding. 
 
Title： 
A randomized, double-blind, parallel-controlled, multi-center 
clinical trial was conducted to evaluate the efficacy and safety 
of Xinnaoning capsule in the treatment of chronic stable angina 
pectoris (Qi stagnation and blood stasis syndrome). 
Version 
number： 
V1.1 
Version 
date：  
January 18, 2018 
 
 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Organization： 
Signature of main researcher： 
Date： 
 
 
 
Clinical trial of Xinnaoning 
Capsule 
Bidder's signature page 
1. I am responsible for initiating, applying, organizing, funding and monitoring 
this clinical trial.             
2. Our company is responsible for the financial compensation for the treatment of 
subjects who suffer from damage or death related to the clinical trial, and provides 
legal and economic guarantees to the researchers.             
3. I agree to carry out this test in accordance with all applicable regulations and 
guidelines.             
4. I agree that all electronic signatures will be equally handwritten and legally 
binding. 
  
 
 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Title： 
A randomized, double-blind, parallel-controlled, multi-center 
clinical trial was conducted to evaluate the efficacy and safety 
of Xinnaoning capsule in the treatment of chronic stable angina 
pectoris (Qi stagnation and blood stasis syndrome). 
Version 
number： 
V1.1 
Version 
date：  
January 18, 2018 
 
 
Bidder: Guizhou Jingcheng Pharmaceutical Co., Ltd. 
Signature of Project Leader: 
Date： 
 
 
 
 
Clinical trial of Xinnaoning 
capsule 
Statistician's signature page 
1. I promise that the statistical data of this experiment are true 
and accurate.             
2. I agree to carry out this test in accordance with all applicable 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
regulations and guidelines.             
3. I agree to maintain the confidentiality of all information obtained 
or related to this test.             
4. I agree that all electronic signatures will be equally handwritten 
and legally binding. 
  
Title： 
A randomized, double-blind, parallel-controlled, multi-center clinical trial 
was conducted to evaluate the efficacy and safety of Xinnaoning capsule 
in the treatment of chronic stable angina pectoris (Qi stagnation and blood 
stasis syndrome). 
Version 
number： 
V1.1 
Version 
date：  
January 18, 2018 
 
 
Statistical Unit: Beijing Huaxia Zhongchuang Medical Science and 
Technology Research Institute 
Statistician's signature: 
Date： 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Clinical trial of Xinnaoning 
capsule 
Inspector's signature page 
1. I promise to ensure that the rights and interests of subjects in clinical trials are 
guaranteed.             
2. I undertake to perform the duties of the Ombudsman in accordance with this 
scheme and all applicable regulations and guidelines.             
3. I promise that the test records and reports are true, accurate and complete.             
4. I agree to maintain the confidentiality of all information obtained or related to 
this test.             
5. I agree that all electronic signatures will be equally handwritten and legally 
binding. 
Title： 
A randomized, double-blind, parallel-controlled, multi-center clinical trial 
was conducted to evaluate the efficacy and safety of Xinnaoning capsule 
in the treatment of chronic stable angina pectoris (Qi stagnation and blood 
stasis syndrome). 
Version 
number： 
V1.1 
Version 
date：  
January 18, 2018 
 
 
 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Contract Research Organization：Beijing Duheng for Drug Evaluation and 
Research Co., Ltd. (DDER) 
Signature: 
Date： 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
Enclosure 1 Coronary Heart Disease Subject Sports 
Manual Coronary Heart Disease Subject Sports Manual 
The formulation of exercise methods for subjects with coronary heart disease is 
based on the patient's condition, age, sports history and hobbies. Clinicians will tell 
patients what activities should be carried out, how to master the amount of exercise 
and matters needing attention. The following will introduce the specific content of 
exercise methods for coronary heart disease subjects.             
1. When can coronary heart disease subjects exercise?             
1) Normal blood pressure and pulse can be used for exercise.             
2) Exercise after noon is better: Angina pectoris, myocardial infarction and 
sudden death often occur from 5 am to 11 noon due to high tension of coronary artery 
in the morning and morning. The most suitable time for subjects with coronary heart 
disease is 7-9 pm. If some people are used to exercise in the morning, they should 
drink a large glass of water on an empty stomach before exercise.             
3) Controlling the amount of motion;             
4) No competitive sports activities;             
5) Step by step and persevere;             
6) inappropriate activities before and after meals: in principle, no exercise within 
2 hours after meals, no meals or strong tea within 1 hour after exercise;             
7) Don't take a bath immediately after exercise.             
8) Prepare and relax before exercise;             
9) Be in a good mood;             
10) Avoid direct sunlight and windward exercise;             
2. When can coronary heart disease subjects not exercise?             
1) In quiet conditions, angina attacks often occur, and all kinds of coronary heart 
disease can not be controlled by treatment.             
2) mild activity, i.e. palpitation, shortness of breath, wheezing or accompanied by 
cardiac insufficiency;             
3) those who have serious arrhythmia, tachycardia, bradycardia, atrioventricular 
block and can not be controlled by medication;             
4) Acute infection subjects;             
5) accompanied by severe hypertension;             
6) Patients with diabetes mellitus and uncontrolled condition after treatment;             

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
7) Severe stenosis of three coronary arteries ranged from 80% to 90%.             
8) Myocardial infarction with pericarditis and myocarditis;             
9) Those with obvious myocardial ischemia, thrombophlebitis or recent history 
of embolism.             
3. Notices for exercise of subjects with coronary heart disease:             
1) Avoid training in bad weather, training before noon or afternoon in winter and 
early morning or evening in summer.             
2) When walking, avoid windward, upper and lower steps and explosive force;             
3) Avoid excessive exertion of upper limbs, especially lifting weights;             
4) Avoid emotional excitement, tension and anger. In such cases, stop exercising 
and learn to relax.             
5) When you feel tired, chest pain, dizziness, shortness of breath, whatever you 
are doing, you should stop and rest immediately.             
6) Do not exceed the target heart rate prescribed by the doctor.             
7) insist on taking medicine according to doctor's advice. Do not randomly add 
or subtract prescribed medicines by doctors; if some acute diseases occur, such as 
colds, diarrhea, etc., stop training.             
4. Motion Method             
1) Type of exercise: Walking, jogging, cycling or fitness bike, swimming and 
other sports are more suitable for coronary heart disease subjects. Because these 
sports belong to low to moderate intensity sports, mainly endurance sports. The 
energy metabolism of these exercises is mainly in the form of aerobic metabolism, so 
it is called "aerobic exercise" in medicine. Long-term exercise can improve the body's 
oxygen carrying capacity and cardiopulmonary function.             
2) Volume of exercise: It is mainly composed of intensity, duration and 
frequency of exercise, which can be coordinated with each other. 
① The intensity of exercise is an important index to ensure that the effect of 
exercise is achieved without causing danger.             
Exercise intensity can be divided into three levels (low intensity, medium 
intensity and high intensity). It is measured by the amount of oxygen consumption 
during exercise. The greater the oxygen consumption, the greater the intensity of 
exercise. However, because it is difficult to measure oxygen consumption in clinical 
practice, heart rate is often used as the most practical index to measure exercise 

Clinical trial scheme of Xinnaoning capsule                   Programme number：DHZD-XNNJN-001                        
Version number：V1.1   Version date：January 26，2018 
intensity in actual exercise. The subjects only needed to count their own pulse for 15 
seconds, multiplied by 4, to get a heart rate per minute. But this method is only 
suitable for subjects without arrhythmia. The highest heart rate at low and moderate 
intensity exercise was 100 beats per minute and 100-120 beats per minute 
respectively.             
Generally speaking, subjects with coronary heart disease can exercise at low to 
moderate intensity. 
② Number of exercises: exercise 3 to 5 times a week to achieve the purpose of 
calcination. 
③ Exercise time: 30-40 minutes each time, including 5-10 minutes of 
preparation exercise; 15-20 minutes of formal exercise, during which the expected 
heart rate can be achieved; 5-10 minutes of finishing exercise. 
3) Generally speaking, the slight increase of systolic blood pressure (systolic 
blood pressure does not exceed 20 mmHg) and the increase of heart rate (the ratio of 
heart rate to activity does not exceed 20 beats/min or the maximum heart rate does not 
exceed 120 beats/min) after exercise are normal reactions. But if there are shortness of 
breath, angina pectoris, arrhythmia, dizziness, nausea, paleness and long-term fatigue, 
insomnia and other discomforts after the activity, it is suggested that this exercise 
should be reduced or suspended in the next exercise.