Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06092736 |
| Other study ID # |
11671808 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
December 18, 2018 |
| Est. completion date |
June 30, 2028 |
Study information
| Verified date |
September 2023 |
| Source |
Qilu Hospital of Shandong University |
| Contact |
Yun Zhang, PhD |
| Phone |
+86-18560086626 |
| Email |
zhangyun[@]sdu.edu.cn |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Coronary microvascular disease (MVD) refers to exertional angina or myocardial ischemia
caused by abnormal structure and/or function of precoronary arterioles and arterioles under
the action of various pathogenic factors. The symptoms of patients with coronary
microvascular disease are mainly exertion-related chest pain episodes.
The basic and clinical researches of the traditional Chinese medicine compound Danshen
dropping pills have found that it can improve vascular endothelial function and relieve
angina pectoris, and it is widely used in clinical practice.
This is a randomized, double-blind, placebo-controlled, multicenter clinical study of
Compound Danshen Dropping Pills and blank control in patients with microvascular angina
pectoris.
The experimental drug and control drug of this clinical trial were selected according to the
ratio of 1:1 patients were enrolled in the pre-experiment.
After the selected patients signed the informed consent, they were divided into a compound
Danshen dripping pill treatment group and a placebo group according to a random,
double-blind, placebo-controlled method. Dosage of Compound Danshen Dropping Pills or
placebo: 20 capsules each time, 3 times a day, for a total of 6 months. Follow-up was
performed every 2 months for a total of 6 months.
Primary study endpoints is the difference of the left anterior descending coronary flow
reserve (CFR) measured by ultrasound between the two groups compared with the baseline.
Secondary study endpoint include the Number of angina attacks per week, the time of angina
pectoris and the time of ischemic ST segment depression in exercise test.
Description:
1. Research Background Coronary microvascular disease (MVD) is a clinical syndrome refers
to laboratory evidence of exertional angina or myocardial ischemia caused by structural
and/or functional abnormalities of precoronary arterioles and arterioles under the
influence of multiple pathogenic factors.. The main symptoms of patients with coronary
microvascular disease are exertion-related chest pain attacks. It is difficult to
distinguish patients with coronary microvascular disease from patients with severe
coronary stenosis based on symptoms alone. However, the following clinical
characteristics suggest that patients have coronary microvascular disease. It is more
likely. First of all, it is more common in women, accounting for about 56%-79% of
patients with coronary microvascular disease. However, most female patients with
coronary microvascular disease have their first symptoms after menopause, which is no
different from traditional female coronary heart disease patients. Secondly, most of the
symptoms are induced by exertion, but it is not uncommon to have patients with silent
chest pain. There are fewer patients with coronary microvascular disease who simply
present with silent chest pain. Impaired coronary dilatation, increased sympathetic
stimulation and sensitivity, and exercise-mediated coronary constriction can lead to the
development of coronary microvascular dysfunction and reduced coronary flow reserve.
Long-term recurrent angina pectoris attacks affect the patient's quality of life.
Patients with significantly reduced coronary blood flow reserve or myocardial perfusion
reserve, especially female patients, may have a higher incidence of adverse
cardiovascular events.
Regarding drug treatment, traditional anti-ischemic treatment methods are currently
recommended, including β- blockers, calcium ion antagonists and nitrates. If symptoms
persist, other drugs include angiotensin-converting enzyme inhibitors, statins,
ivabradine , ranolazine , and estrogen drugs. However, there is no specific clinical
drug treatment. Basic and clinical studies of the traditional Chinese medicine Compound
Danshen Dripping Pill have found that it can improve vascular endothelial function and
relieve angina pectoris, and is widely used in clinical practice. However, its effect on
coronary reserve function and angina pectoris in coronary microvascular disease needs
further clinical research to confirm.
2. Study drug The main drug studied in this study is Compound Danshen Dripping Pill.
Compound Danshen Dripping Pills (Compound Danshen Dripping Pills, produced by Tasly
Holding Group Co., Ltd.) is a compound traditional Chinese medicine preparation composed
of Salvia miltiorrhiza, Panax notoginseng, and Borneol. In 1994, it was approved as a
drug for the treatment of coronary heart disease and angina pectoris. It has good
clinical efficacy and has It has the characteristics of fast onset, low toxicity, small
adverse reactions and high safety.
The active ingredients of compound Danshen dripping pills are water-soluble phenolic acids
such as salvia miltiorrhiza and Panax notoginseng saponins. During the preparation process,
borneol and auxiliary materials are added, and a highly dispersed solid dispersion is made
through a specific process. The active ingredients of the drug have high purity, are evenly
dispersed, and can be quickly absorbed through the mucous membrane. The dripping pills have
good solid dispersion effect. The principle is to melt the drug ingredients and matrix into a
solid solution, and the active ingredients of the drug are in the molecular state or in
extremely fine form. The crystalline state is highly uniformly dispersed in the matrix, with
fast drug dissolution and higher bioavailability. It can be taken sublingually and can
quickly relieve angina pectoris and chest tightness.
Compound Danshen Dripping Pill has achieved a full-process quality control method from
medicinal materials, intermediates to preparations (GAP-GEP-GMP) through the multi-factor
fingerprint quality control system of compound oral Chinese medicine preparations, further
improving the full-process quality control system of Compound Danshen Dripping Pill , after
testing and analyzing nearly 200 batches of Compound Salvia Miltiorrhizae Dropping Pills
Extract and Compound Salvia Miltiorrhizae Dropping Pills, the similarity is over 90%, and the
quality of the products is stable between batches. It has been confirmed through the
toxicology study of Compound Danshen Dripping Pill and the clinical use of hundreds of
millions of people: it has no toxicity, few adverse reactions, and is safe and reliable for
long-term use.
As a Chinese patent medicine for the treatment of stable angina pectoris, Compound Danshen
Dripping Pill are included in Category A of the 2018 National Essential Drugs Catalog and the
2019 National Basic Medical Insurance, Work Injury Insurance and Maternity Insurance Drug
Catalogue. Under the name of "Compound Danshen Dripping Pill", it has been written into more
than 20 national medical guidelines or consensus, 15 of which involve the cardiovascular
field, including "Guidelines for Rational Medication in Coronary Heart Disease (2nd
Edition)", "Acute Myocardial Medication "Guidelines for the Diagnosis and Treatment of
Infarction by Integrated Traditional Chinese and Western Medicine", "Chinese Expert
Recommendations on the Clinical Application of Compound Danshen Dripping Pill", "Expert
Consensus on the Diagnosis and Treatment of Atherosclerosis by Integrated Traditional Chinese
and Western Medicine", etc.
In terms of international evidence-based research, large-sample, randomized, double-blind,
placebo-controlled RCT studies were used, and 1,004 patients were included in phase III
clinical studies at 127 centers in 9 countries/regions around the world, indicating that the
US FDA-Phase III The main clinical efficacy indicators: significantly increase the patient's
exercise flat time and improve exercise tolerance. Compared with the increase time of
exercise oxygen tolerance of similar drugs, Compound Danshen Dripping Pill has obvious
advantages . Secondary efficacy indicators: effectively reduce the number of angina attacks
per week and significantly reduce the weekly nitroglycerin dosage.
In terms of domestic evidence-based research: 1011 studies on Compound Danshen Dripping Pill
for the treatment of stable angina, 16 Meta-analyses, with a total enrollment of more than
100,000 people; 137 studies on the treatment of peri-PCI/ thrombolysis period , the total
number of participants exceeds 10000 ; there are 36 studies on Compound Danshen Dripping Pill
improving coronary microcirculation disorders, filling the gap in Western medicine treatment.
Systematic study of Compound Danshen Dripping Pill combined with Western medicine in the
treatment of coronary heart disease angina pectoris: 21 articles were included, with a total
number of cases of 2229. Compound Danshen Dripping Pill combined with Western medicine can
benefit patients with coronary heart disease angina pectoris, especially in improving
clinical symptoms and electrocardiogram . It has outstanding effects on ischemic state and
regulating cholesterol levels.
A meta-analysis based on PubMed, EMBASE, CNKI, and Wanfang databases studied the efficacy of
aspirin combined with Compound Danshen Dripping Pill in the treatment of coronary heart
disease. The analysis included 14 randomized controlled trials with a total of 1,367
patients. The results showed that the combination Compared with aspirin alone, the drug can
achieve more significant therapeutic effects in relieving angina pectoris symptoms and
lowering blood lipids. Lu Yuhong et al. randomly divided 128 patients with coronary heart
disease into groups. The control group took oral aspirin on the basis of conventional
treatment, and the observation group took Danshen Dropping Pills on the basis of conventional
treatment. After 2 months, the total clinical effective rate of the patients in the
observation group was significantly higher than Control group. Compared with before
treatment, the maximum platelet aggregation rate and thromboxane B2) levels of the two groups
of patients were significantly reduced, and the decrease in the observation group was more
obvious than that in the control group . The "Guidelines for the Diagnosis and Treatment of
Integrated Traditional Chinese and Western Medicine in Acute Myocardial Infarction", led by
Academicians Chen Keji, Academician Ge Junbo, and Professor Zhang Minzhou, were formulated in
conjunction with experts in the fields of traditional Chinese medicine, Western medicine,
integrated traditional Chinese and Western medicine, and methodology across the country. The
guideline clearly states that Compound Danshen Dripping Pill are recommended for the
treatment of acute myocardial infarction. The recommendation level is the highest in the
guideline. Compound Danshen Dripping Pill can relieve chest pain, reduce the patient's risk
of cardiac death, and improve the patient's cardiac function. and the role of quality of
life.
3. Research purpose A randomized, double-blind, placebo-controlled, multi-center clinical
study of Compound Danshen Dripping Pill and blank control was conducted in patients with
microvascular angina pectoris .
4. research design 4.1 Study title and registration The Chinese name of this project is:
Microvascular Angina Intervention with Compound Danshen Dripping Pill. English name:
Microvascular Angina Intervention with Compound Danshen Dripping Pill. Referred to as MAIDS
Study.
4.2 Research design : Randomized, double-blind, placebo parallel-controlled, multi-center
clinical study.
4. 3 dosing regimens (double-blind single simulation)
1. Placebo group: Placebo (the appearance is the same as Compound Danshen Dripping Pill ,
main ingredient: starch. Production unit: Tianjin Tasly Co., Ltd.), taken orally after
meals, 3 times a day, 20 pills each time .
2. Treatment group: Compound Danshen Dripping Pill (Tianjin Tasly Co., Ltd.), taken orally
after meals, 3 times a day, 20 pills each time .
Note: The batch number on the drug packaging is unified as " 161299 ". 5. Research objects
5.1 Source of patients: patients with chest pain who had no obvious coronary artery stenosis
on coronary angiography or coronary CT examination were admitted to the hospital outpatient
clinics and wards .
5.2Selection criteria _
1. With typical symptoms of exertional angina;
2. Coronary CTA or angiography with normal coronary artery or <50% stenosis, or <50%
residual coronary stenosis after revascularization;
3. Ischemic downward shift of the ST segment is found in the electrocardiogram at rest or
during exercise stress (horizontal or downsloping downward shift behind the J point
>0.1mv, lasting 0.08s );
4. Transthoracic ultrasound before and after intravenous adenosine injection to check the
anterior descending coronary artery blood flow reserve test CFR <2.5;
5. The patient agreed to participate in this study. 5.3 Exclusion criteria (1) Aged less
than 30 years old or older than 75 years old; (2) Have a history of carotid
endarterectomy or stent implantation, and have a history of stroke ; (3) Myocarditis,
pericardial disease, valvular disease, and cardiomyopathy; (4) Difficult-to-control
diabetes (fasting blood glucose >7.0 mmol/L); ( 5 ) Uncontrollable hypertension (SBP>150
mmHg and/or DBP>90 mmHg); ( 6) Familial hypercholesterolemia; ( 7 ) Takayasu arteritis;
( 8 ) Those who are pregnant or lactating, or those who intend to have a child within
one year, or those who have not taken effective contraceptive measures during the
childbearing age; ( 9 ) Abnormal liver function (serum GPT level exceeds 3.0 times the
upper limit of normal value) or abnormal renal function (serum creatinine level exceeds
2 mg/dl); ( 10 ) Other clinically significant respiratory, digestive, blood, infection,
immune, endocrine, neuropsychiatric, tumor diseases, etc., which may cause serious
danger to patients; ( 11 ) Take K channel openers and traditional Chinese medicine
preparations that activate blood circulation and remove blood stasis to improve
microcirculation; (12 ) Those allergic to intra-arterial injection of contrast media,
blood, and blood products; (13) Patients who are participating in other clinical
studies.
6. Research methods 6.1Sample size The experimental drugs and control drugs in this clinical
trial will be selected according to the number of cases in a ratio of 1:1. 100 patients were
enrolled in the preliminary experiment .
6.2 Random grouping The randomization method adopts the central randomization method. The
central randomization system uses DAS2.1.1 software to generate random numbers (00 1 -100)
and drug packaging numbers ( B ZH001-100 ). The random numbers and drug packaging numbers are
separated in the system . The researcher passes the Apply to the system to obtain the drug
packaging number for the subject. The random number and drug packaging number of the same
subject are different, but their corresponding treatment plans are consistent within the
system.
6.3 Research process After signing the informed consent form, the selected patients were
divided into the Compound Danshen Dripping Pill treatment group and the placebo group
according to a random, double-blind, placebo-controlled method. Dosage of Compound Danshen
Dripping Pill or placebo: 3 times a day, 20 pills each time, for a total of 6 months .
Follow-up visits were conducted every 2 months, and the follow-up period was 6 months in
total .
6.4 Screening Phase
1. CTA or CAG examination: Coronary artery CTA or angiography examination shows that the
coronary arteries are normal or stenotic <50%, and coronary epicardial vasospasm is
excluded;
2. Electrocardiogram: Resting or exercise stress test shows ischemic downward shift of ST
segment, horizontal or downward shift behind J point >0.1mv, lasting 0.08s.
3. Laboratory tests: Fasting for more than 6 hours, blood routine, urine routine, fasting
blood glucose, alanine aminotransferase, aspartate aminotransferase, troponin, serum
creatine phosphokinase, urea nitrogen, creatinine , plasma total cholesterol,
triglycerides, hypoglycemia The existing data on density lipoprotein cholesterol,
high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and
prothrombin time during the screening phase can no longer be reviewed.
4. Echocardiogram:
After signing the informed consent form, the following inspections will be performed: See
Appendix 1 for inspection methods.
1. Routine ultrasound examination: two- dimensional dynamic images of left ventricular
parasternal long axis, apical four-chamber, apical two-chamber, apical long axis and
left ventricular apex level, papillary muscle level, and mitral valve level short-axis
sections. At the same time, pulse wave Doppler was used to obtain the diastolic mitral
valve orifice blood flow spectrum, and tissue Doppler was used to obtain the mitral
valve annular motion spectrum. See Appendix 1 for details.
2. Acoustic contrast adenosine test: First, observe the distal left anterior descending
coronary artery under color Doppler guidance, measure the blood flow velocity with
pulsed Doppler ultrasound, and then administer the contrast agent SonoVue (add 8.5ml
sterile saline to one bottle ) bolus injection, followed by slowly injecting 5 ml of
normal saline over 20 seconds, and measuring the blood flow velocity of the distal left
anterior descending coronary artery again . Finally, adenosine 140 µg.kg -1 .min -1 was
given for 6 minutes by continuous intravenous micropump injection. During the injection
process, the coronary blood flow velocity was monitored. Pulse Doppler ultrasound
measured the maximum coronary blood flow velocity in the distal left anterior descending
artery. This could be repeated at the same time. Acoustic contrast enhances spectral
signals.
3. The adenosine test simultaneously records a 12-lead electrocardiogram.
4. After recording the coronary blood flow in the contrast-enhanced ultrasound examination,
the two-dimensional short-axis sections of the left ventricular parasternal long axis,
apical four- chamber heart, apical two-chamber heart, apical long axis and left
ventricular apex level, papillary muscle level, and mitral valve level were recorded.
dynamic images.
6.5 Enrollment and follow-up phase
1. Case grouping 100 patients were selected and randomly divided into Compound Danshen
Dripping Pill group and control group, 50 cases each. Compound Danshen Dripping Pill: 20
pills, three times a day; Placebo: 20 pills, three times a day.
2. Follow-up observation Follow-up observations were conducted at 2 months, 4 months, and 6
months after inclusion, including clinical conditions, laboratory examinations, and
ultrasound examinations. Safety assessment.
7. Efficacy evaluation 7.1 Main observation indicators Difference in left anterior descending
coronary flow reserve (CFR) measured by ultrasound at 6 months compared with baseline.
7.2 Secondary observation indicators
1. Difference in left anterior descending coronary flow reserve (CFR) measured by
ultrasound at 2 months and 4 months compared with baseline.
2. Number of angina attacks per week;
3. The time when angina pectoris occurs in exercise test; 4 ) The time when ischemic ST
segment depression occurs during exercise testing.
8.Safety assessment Including clinical adverse reactions, laboratory indicators, etc. 9.
Adverse event observation and reporting 9.1Definition of Adverse Events Adverse events refer
to any adverse medical event that occurs to a patient in this clinical trial from the time
the patient signs the informed consent form and is selected to participate in the trial to
the last follow-up visit, regardless of whether this event is causally related to the
above-mentioned drugs. .
NOTE: An adverse reaction may be any discomfort and unconscious signs (including abnormal
laboratory test results), symptoms, or disease (new or worsening) related to the medication.
Events that meet the definition of adverse events include:
- Exacerbation of an existing chronic or intermittent disease, including increased
frequency and/or intensity.
- A disease that is newly detected or diagnosed after taking the investigational drug,
even though it may have been present before the trial began.
- Signs, symptoms, or clinical sequelae suspected of being caused by an interaction.
- Signs, symptoms or clinical sequelae caused by suspected overdose of the investigational
drug or concomitant medication (overdose itself is not an adverse event / serious
adverse event).
- " Lack of efficacy " or " failure to achieve the expected pharmacological effect "
itself is not reported as an adverse event or serious adverse event. However, signs,
symptoms, and/or clinical sequelae due to lack of efficacy will also be reported as
adverse events or serious adverse events if they meet the definition of an adverse event
or serious adverse event.
Events that do not meet the definition of an adverse event include:
- Medical or surgical procedure (e.g., endoscopy, appendectomy); the event leading up to
the procedure is an adverse event.
- Situations in which adverse medical events would not occur (social security and / or
admission facilitation).
- There was no worsening of pre-existing diseases or conditions that were present or
detected at the start of the trial, only expected day-to-day fluctuations.
- disease being studied , or the expected progression, signs, or symptoms of the
disease being studied. Unless the situation is more serious than expected.
Definition of serious adverse event " serious adverse event " is an adverse event that can
occur at any dose and will:
- cause death;
- threatening life; Note: " Life-threatening " means that the subject is in danger of
death when the event occurs, not that death could theoretically result if the event were
more serious.
- Requires hospitalization or prolonged hospitalization; Note: Typically hospitalization
refers to a subject staying in the hospital or emergency room (usually at least
overnight) to receive observation and/or treatment that cannot be completed in the
doctor's office or outpatient clinic. Complications that occur during hospitalization
are considered adverse events. An event is classified as a serious adverse event if the
complication prolongs hospitalization or meets the criteria for any other serious
adverse event. When it cannot be determined whether " hospitalization " occurred or was
necessary, it will be treated as a serious adverse event.
Elective hospitalization that does not worsen a pre-existing condition compared with baseline
is not an adverse event.
- Causes disability, or affects the ability to work and live; Note: " Disability " refers
to a substantial impairment of an individual's ability to carry out normal life. It does
not include discomforts of little clinical significance, such as common headaches,
nausea, vomiting, diarrhea, influenza, and accidental trauma (such as sprained ankles),
which may affect the quality of daily life but will not constitute a substantial
disruption.
- Cause congenital malformations; In other cases, medical or scientific judgment should
determine whether adverse event reporting is appropriate. For example, some important
medical events may not be immediately life-threatening, leading to death or
hospitalization, but may harm subjects or require drug or surgical intervention to avoid
the serious adverse events listed above. These events should also be considered serious
adverse events, such as invasive or malignant cancer, allergic bronchospasm requiring
close monitoring in the emergency room or at home, hematologic cachexia, or convulsions
that do not result in hospitalization, drug dependence, or drug abuse.
9.2 Adverse drug reactions Definition: Refers to harmful reactions that occur under normal
usage and dosage of qualified drugs and have nothing to do with the purpose of medication.
Causal judgment indicators for adverse reaction judgment:
Item 1 : Is there a reasonable sequence between the time of starting medication and the time
when the suspicion appears? Item 2 : Whether the suspected adverse reaction conforms to the
known adverse reaction type of the drug; Item 3: Whether the suspected adverse reaction can
be explained by the patient's pathological condition, concomitant medications, concomitant
therapies, or previous therapies; Item 4 : After stopping the drug or reducing the dose,
whether the suspected adverse reactions are reduced or disappeared; Item 5 : Whether the same
reaction reappears after using the suspected drug again.
Causality judgment criteria: Judgment based on the order of the above five judgment
indicators.
It is up to the investigator to evaluate possible associations between adverse events, trial
drugs, and concomitant medications according to the table below.
Adverse reaction cause and effect judgment table
critical result Judgment index Project 1 Project 2 Project 3 Item 4 Item 5 Definitely related
+ + - + + probably related + + - + ? may be relevant + + ± ± ? suspicious + - ± ± ?
Impossibly related + - + - -
Explanation: + Affirmation, - Negation, ± Difficult to affirm or deny,? The situation is
unknown.
1.Based on the table above, determine the relationship between the following grade 5 adverse
events and the drug.
( 1 ) Definitely related, ( 2 ) Probably related, ( 3 ) Possibly related, ( 4 ) Suspicious, (
5 ) Impossibly related.
2. The incidence rate of adverse reactions is calculated using the total number of 1 + 2 + 3
+ 4 cases as the numerator, and all selected cases that can be evaluated for adverse
reactions as the denominator.
9.3Recording of adverse events on the basis of comprehensive consideration of comorbidities
and concomitant medications, their relevance to the experiment should be evaluated. The
relevance of the drug and documented in detail by the physician.
If an adverse event is discovered, the observing physician can decide whether to terminate
the observation based on the condition. Cases of drug discontinuation due to adverse events
should be followed up and investigated, and the results should be recorded in detail. If any
abnormality in safety test indicators ( blood, urine, stool routine, electrocardiogram, liver
function, kidney function ) occurs during or after treatment , the adverse event form should
be filled in in a timely manner, reviewed at an appropriate time, and communicated with the
subject A comprehensive analysis will be conducted on the onset, treatment, etc. to determine
whether it is related to the experimental drug.
9.4 Handling of serious adverse events For any serious adverse events that occur during the
trial ( including events requiring hospitalization, prolonged hospitalization, disability,
affecting work ability, endangering life or death, causing congenital malformations, etc.)
during the clinical trial , the researcher shall immediately respond to the patient's
request. In addition to taking emergency measures, the subject must also immediately report
to the ethics committee of the National Drug Clinical Trial Institution of Shandong
University Qilu Hospital and the main research unit Tianjin Tasly Co., Ltd., the unit
responsible for the research. The content of the report of serious adverse events should
include: patient's name, random number, length of study participation, start date and stop
date of serious adverse events, maximum intensity of serious adverse events, possible
relationship between serious adverse events and study drugs, due to serious Whether the
adverse event required a change in the study drug, the treatment given to the patient as a
result of the serious adverse event, concomitant medications if the serious adverse event
occurred, and the outcome of the serious adverse event.
10. Data management and statistical analysis 10.1Data management
1. Establish database: The data administrator establishes an EXCEL database based on the
research plan and CRF, and sets up logical verification according to the data
verification plan (DVP). Release for use after passing the test.
2. Data entry: Data entry personnel conduct independent double entries and double checks.
Inconsistent results will be checked and corrected item by item against the CRF until
the results are completely consistent.
3. Data questions and answers: After data entry is completed, the data administrator
conducts question screening according to DVP's manual verification plan, opens database
access to researchers, and answers questions remotely. The data administrator responds
to questions and can issue questions again if necessary until the data is "clean".
4. Database locking: After the main researcher, statistical analysts and data managers
jointly sign the "database lock record", the data administrator locks the database.
5. Database submission: The data administrator submits the database to the statistician.
10.2 Statistical analysis data set
1. Full analysis set (FAS): a set of all randomly enrolled cases that used the study drug
at least once.
2. Per-protocol set (PPS): It is a data set generated by subjects who are fully compliant
with the trial protocol. Compliance includes the treatment received, the availability of
primary endpoint measurement, and no major impact on the trial protocol. Violation etc.
PPS analysis was used for the primary efficacy outcome measure.
3. Safety Data Set (SS): Actual data that received at least one treatment and had
post-treatment safety indicator records. The incidence of adverse reactions was based on
the number of SS cases as the denominator.
10.3Statistical methods 9.3.1 Subject distribution analysis
1. List the number of subjects selected and completed the trial, and determine three
analysis data sets (FAS, PPS, SS).
2. Conduct a classification analysis on the reasons for not entering PPS and calculate the
number of subjects in different categories.
3. Make a detailed list of group classifications, including the reasons for not being
included in PPS/FAS/SS.
4. Draw a flow chart of subject distribution. 10.3.2 Demographic data and baseline analysis
Descriptive statistics Demographic information and other baseline characteristic values:
1. Calculate the number of cases, mean, standard deviation, 95%CI, minimum and maximum
values for continuous variables.
2. Count and grade data calculation frequency and composition ratio.
3. Inferential statistical results (P values) are listed as descriptive results. 10.3.3
Medication compliance and concomitant medication analysis
1. Calculate the percentage of subjects with medication compliance in the range of
80%-120%, and use the χ2 test or Fisher's exact probability method to compare
differences between groups.
2. Medication exposure, use t test to compare differences between groups.
3. Calculate the percentage of subjects with combined medications, and use the χ2 test or
Fisher's exact probability method to compare differences between groups.
10.3.4 Efficacy analysis (1) Analysis of main efficacy indicators FR measured by ultrasound
at 6 months and the baseline between the two groups was compared using t test.
(2) Analysis of secondary efficacy indicators FR measured by ultrasound at 2 months and 4
months and the baseline was compared between the two groups using t test;
- For the number of angina attacks per week, t test was used to compare the differences
between groups;
- For the time of occurrence of angina pectoris in exercise test, t test was used to
compare the differences between groups;
- The time when ischemic ST segment downward shift occurs in exercise test, and
the t test is used to compare the differences between groups; 10.3.5 Security
analysis (1) Calculate the incidence of adverse events/reactions, serious
adverse events/reactions, and adverse events/reactions leading to dropout.
(2) List a detailed list of cases of various adverse events/reactions, serious
adverse events/reactions, and adverse events/reactions leading to dropout.
(3) List the crosstabs of laboratory tests and electrocardiograms before and
after medication.
(4) Descriptive statistics of changes from baseline in laboratory
examinations, electrocardiograms, and vital signs, and actual measured values.
(5) Make a detailed list of abnormal values in laboratory tests,
electrocardiograms, and physical examinations.
10.3.6Statistical software
1. Analysis using S PSS software.
2. All statistical tests adopt two-sided tests, and a P value less than or equal to 0.05
will be considered as statistically significant.
3. Detailed statistical methods will be provided in the statistical analysis plan.
