Clinical trial NCT02694848: Clinical Study of Combination Therapy for Angina of Coronary Heart Disease With Aspirin and Salvianolate Injection
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Angina
Lead sponsor: China Academy of Chinese Medical Sciences
Sponsor class: OTHER
Collaborators: name: Xiyuan Hospital of China Academy of Chinese Medical Sciences
name: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
name: General Hospital of Beijing PLA Military Region
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
First posted: 2016-03-01
Enrollment: 120
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of thromboela-stogram（R time,K time,α angle,MA、CI、TPI）
timeFrame: Change from base line on the tenth day
Secondary outcomes:
measure: Change of symptom score of the Seattle Angina Questionnaiire(SAQ)
timeFrame: Change from base line on the tenth day
measure: Change of ECG abnormalities
timeFrame: Change from base line on the tenth day
measure: Change of score of Traditional Chinese Medicine(TCM) symptom curative effect rating scale
timeFrame: Change from base line on the tenth day
measure: Change of platelet aggregation measured by light transmittance aggregometry(LTA)
timeFrame: Change from base line on the tenth day
measure: Change of serum lipids（TC、TG、HDL-C、LDL-C）
timeFrame: Change from base line on the tenth day
measure: Change of fasting blood glucose
timeFrame: Change from base line on the tenth day
measure: The blood concentration of magnesium lithospermate B
timeFrame: 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)
measure: The blood concentration of salicylic acid
timeFrame: 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 outcomes:
measure: Change of PT
timeFrame: Change from base line on the tenth day
measure: Adverse events
timeFrame: Change from base line on the tenth day
measure: Change of basic life sign
timeFrame: Change from base line on the tenth day
measure: Gastrointestinal symptoms
timeFrame: Change from base line on the tenth day
measure: Change of stool routine
timeFrame: Change from base line on the tenth day
measure: Change of routine blood test
timeFrame: Change from base line on the tenth day
measure: Change of urine routine
timeFrame: Change from base line on the tenth day
measure: Change of liver function
timeFrame: Change from base line on the tenth day
measure: Change of renal function
timeFrame: Change from base line on the tenth day
measure: Change of fecal occult blood
timeFrame: Change from base line on the tenth day
measure: Change of APTT
timeFrame: Change from base line on the tenth day
measure: Change of TT
timeFrame: Change from base line on the tenth day
measure: Change of FIB
timeFrame: Change from base line on the tenth day
Locations:
city: Beijing
country: China
facility: Xiyuan Hospital of China Academy of Chinese Medical Sciences
state: Beijing
Study officials:
affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences
name: Yanming Xie, Study Chair
role: STUDY_CHAIR
References:
citation: 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.