Clinical Study of Combination Therapy for Angina of Coronary Heart Disease With Aspirin and Salvianolate Injection

Clinical Study of Combination Therapy for Angina of Coronary Heart Disease With Aspirin and Salvianolate Injection Based on Population Pharmacokinetics and Therapeutic Effect:A Randomized, Controlled Trial

To evaluate the therapeutic evaluation of combination therapy with aspirin and salvianolate injection based on the population pharmacokinetics and TEG.A prospective, multicenter, randomized, controlled clinical trial is used.A total of 120 patients will be recruited and will be divided into three groups,respectively salvianolate injection group,aspirin group and salvianolate injection and aspirin group，and the course of treatment is 10 days.

Study Overview

• Status: Unknown
• Conditions: Angina
• Intervention / Treatment: Drug: Salvianolate injection; Drug: Aspirin

Detailed Description

1. Effectiveness evaluation:Primary Outcome Measure:Change of TEG（R time, K time, α angle, MA,CI,TPI）.Secondary Outcome Measures: Change of symptom score of the Seattle Angina Questionnaiire(SAQ).Change of ECG abnormalities.Change of score of traditional Chinese medicine(TCM) symptom curative effect rating scale. Change of platelet aggregation measured by light transmittance aggregometry(LTA).Change of serum lipids（TC、TG、HDL-C、LDL-C）.Change of fasting blood glucose.Population pharmacokinetics test(the detection of the blood concentration of magnesium lithospermate B and salicylic acid).
2. Safety evaluation:Change of PT,APTT,TT,FIB.Adverse events.Change of basic life sign.Gastrointestinal symptoms.Change of stool routine.Change of routine blood test.Change of urine routine.Change of liver function.Change of renal function.Change of fecal occult blood.
3. Number of participants:120 participants will be divided into three groups, the salvianolate group (n=40), the aspirin group(n=40) and the combination therapy group of salvianolate injection and aspirin(n=40).
4. Interventions:salvianolate injection group: salvianolate injection, intravenously infusion,0.2g/time, once a day; other routine treatment according to the condition of the disease.Aspirin group: aspirin, oral administration method,0.1g/time, once a day; other routine treatment according to the condition of the disease.Salvianolate injection and aspirin group: salvianolate injection, intravenously infusion,0.2g/time, once a day; aspirin, oral administration method,0.1g/time, once a day; other routine treatment according to the condition of the disease.
5. Course of treatment：10 days.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100091
      • Xiyuan Hospital of China Academy of Chinese Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient age 35-75 years old
• Grade II diagnostic criteria for chronic stable angina pectoris
• Diagnostic criteria of blood stasis type
• Signed informed consent

Exclusion Criteria:

• Drug allergy to the test
• There is a family or personal history of hemorrhagic disease
• Platelet count < 100 * nine times square 10/L or > 450 *nine times square 10/L
• Hemoglobin < 90g/L
• ALT, AST higher than the upper limit of 2 times, BUN, Cr higher than the upper limit
• Drugs such as the use of clopidogrel, clopidogrel, Hua Falin or heparin in the last 2 weeks to take blood circulation drugs or other antiplatelet, anticoagulant or non steroidal anti-inflammatory drugs
• Heart failure three degrees, two degrees in patients with heart failure
• A history of trauma or surgery in the past 2 weeks
• Combined coronary heart disease myocardial infarction and cerebral blood vessels, liver, kidney, hematopoietic system severe primary disease, malignant tumor, mental disease patients, as well as hyperthyroidism, cervical spondylosis, stomach and esophageal reflux and other patients with chest pain
• Organ transplantation, AIDS, long-term use of immunosuppressive agents and other immune deficiency
• Pregnant or lactating women
• Other clinical trial participants who are taking part in the evaluation of the results of this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Salvianolate injection group; Salvianolate injection,intravenously infusion,0.2g/time,once a day;other routine treatment according to the condition of the disease	Drug: Salvianolate injection; Traditional Chinese medicine injection，a kind of innovative drugs developed by Shanghai institute of materia medica, Chinese academy of sciences after 13 years of research and development.the content of magnesium acetate was 80%, and the other 20% were magnesium acetate.It has the function of promoting blood circulation,removing blood stasis and blood stasis,and is used for treating coronary heart disease with stable angina pectoris.
Active Comparator: Aspirin group; Aspirin,oral administration method,0.1g/time,once a day;other routine treatment according to the condition of the disease	Drug: Aspirin; Molecular chemical formula: C9H8O4,molecular structure type: CH3COOC6H4COOH. It has the role of anti thrombosis In vivo, and it can inhibit the release of the platelet reaction, inhibit platelet aggregation, which is related to the reduction of TXA2 generation. Clinically itused to prevent the onset of cardiovascular and cerebrovascular diseases.
Experimental: Salvianolate injection and aspirin group; Salvianolate injection,intravenously infusion,0.2g/time,once a day;aspirin,oral administration method,0.1g/time,once a day;other routine treatment according to the condition of the disease	Drug: Salvianolate injection; Traditional Chinese medicine injection，a kind of innovative drugs developed by Shanghai institute of materia medica, Chinese academy of sciences after 13 years of research and development.the content of magnesium acetate was 80%, and the other 20% were magnesium acetate.It has the function of promoting blood circulation,removing blood stasis and blood stasis,and is used for treating coronary heart disease with stable angina pectoris.; Drug: Aspirin; Molecular chemical formula: C9H8O4,molecular structure type: CH3COOC6H4COOH. It has the role of anti thrombosis In vivo, and it can inhibit the release of the platelet reaction, inhibit platelet aggregation, which is related to the reduction of TXA2 generation. Clinically itused to prevent the onset of cardiovascular and cerebrovascular diseases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of thromboela-stogram（R time,K time,α angle,MA、CI、TPI）	Thromboela-stogram(TEG) Is a reflection of the dynamic changes in blood coagulation (including the formation rate of fibrin, the dissolution of the state and the consistency of the solid, elastic degree) of the index: R time is the latency of the first fibrin plaque formation. K time is to assess the rate at which blood clots reach a certain level. The alpha angle is similar to the K time, but is more comprehensive than the K time, and is not affected by the low coagulation state. MA reflects the maximum amplitude of blood clots. CI is an integrated coagulation index.TPI is the index of platelet kinetics	Change from base line on the tenth day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of symptom score of the Seattle Angina Questionnaiire(SAQ)	SAQ includes 5 dimensions: the degree of physical activity limitation, the stable state of angina pectoris, the frequency of angina attack, the degree of treatment satisfaction, and the recognition of the disease	Change from base line on the tenth day
Change of ECG abnormalities	ECG is the most common method of detection of myocardial ischemia and the diagnosis of angina pectoris	Change from base line on the tenth day
Change of score of Traditional Chinese Medicine(TCM) symptom curative effect rating scale	It includes the description of scores of symptoms, signs of tongue and pulse related to blood stasis syndrome of diagnosis of traditional Chinese medicine	Change from base line on the tenth day
Change of platelet aggregation measured by light transmittance aggregometry(LTA)	The method is widely recognized, and is even considered a gold standard	Change from base line on the tenth day
Change of serum lipids（TC、TG、HDL-C、LDL-C）	Hyperlipidemia is one of the causes of angina. The measurement units of four indicators（TC、TG、HDL-C、LDL-C）are "mmol/L"	Change from base line on the tenth day
Change of fasting blood glucose	It is one of the causes of angina(especially for patients with diabetes).The measurement unit is "mmol/L"	Change from base line on the tenth day
The blood concentration of magnesium lithospermate B	Population pharmacokinetics test is in order to study the relationship between the population pharmacokinetics and clinical outcome. Magnesium lithospermate B is the main effective components of Salvianolate injection.The detection of the blood concentration of magnesium lithospermate B from both salvianolate injection group and salvianolate injection and aspirin group is necessary.	At the discretional two time points from the time point after treatment(0h,0.25h(15min),0.5h,0.75h(45min),1h,1.17h(70min),1.33h(80min),1.67h(100min),2h,2.5h,3h,4h,5h,7h,9h,13h,25h)
The blood concentration of salicylic acid	Population pharmacokinetics test is in order to study the relationship between the population pharmacokinetics and clinical outcome. Salicylic acid is a kind of metabolite of aspirin. The detection of the blood concentration of salicylic acid from both aspirin group and salvianolate injection and aspirin group is necessary.	At the discretional two time points from the time point after treatment(0h,0.5h,1h,1.5h,2h,2.5h,3h,4h,5h,6h,8h,9h,10h,12h)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of PT	An index to reflect the status of the extrinsic coagulation system	Change from base line on the tenth day
Adverse events		Change from base line on the tenth day
Change of basic life sign	In the medical care system, body temperature, blood pressure and pulse are the most important and basic three physiological parameters of the vital signs	Change from base line on the tenth day
Gastrointestinal symptoms		Change from base line on the tenth day
Change of stool routine	The stool routine includes stool properties, lipid droplets, and white blood cell count	Change from base line on the tenth day
Change of routine blood test	The routine blood test includes white blood cell count, neutral cell ratio, lymphocyte ratio, single nuclear cell ratio, red blood cell count, hemoglobin, platelet count	Change from base line on the tenth day
Change of urine routine	The urine routine includes white blood cell count, red blood cell count,urine protein,urine sugar	Change from base line on the tenth day
Change of liver function	The liver function includes glutamic-pyruvic transaminase,glutamic-oxalacetic transaminase	Change from base line on the tenth day
Change of renal function	The renal function includes creatinine,usea nitrogen	Change from base line on the tenth day
Change of fecal occult blood	In order to monitor the safety of the digestive tract (if there is bleeding)	Change from base line on the tenth day
Change of APTT	An index to reflect the status of endogenous coagulation system	Change from base line on the tenth day
Change of TT	An index to reflect the time consuming from the fibrinogen into fibrin	Change from base line on the tenth day
Change of FIB	An index to reflect the content of fibrinogen	Change from base line on the tenth day

Collaborators and Investigators

• Sponsor: China Academy of Chinese Medical Sciences
• Collaborators: Guangdong Provincial Hospital of Traditional Chinese Medicine; Guang'anmen Hospital of China Academy of Chinese Medical Sciences; Xiyuan Hospital of China Academy of Chinese Medical Sciences; General Hospital of Beijing PLA Military Region
• Investigators: Study Chair: Yanming Xie, Study Chair, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences

Publications and helpful links

General Publications

• Lyu J, Xue M, Li J, Lyu W, Wen Z, Yao P, Li J, Zhang Y, Gong Y, Xie Y, Chen K, Wang L, Chai Y. Clinical effectiveness and safety of salvia miltiorrhiza depside salt combined with aspirin in patients with stable angina pectoris: A multicenter, pragmatic, randomized controlled trial. Phytomedicine. 2021 Jan;81:153419. doi: 10.1016/j.phymed.2020.153419. Epub 2020 Dec 10.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): March 1, 2017

Study Registration Dates

• First Submitted: February 14, 2016
• First Submitted That Met QC Criteria: February 24, 2016
• First Posted (Estimate): March 1, 2016

Study Record Updates

• Last Update Posted (Estimate): March 1, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Chest Pain; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Angina Pectoris; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: EBM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No