Clinical trial NCT03306550: Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin
Official title: Research on Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin Based on the Metabolic Enzyme and PK-PD Model
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Angina, Stable
Keywords: drug-drug interaction
Asprin
salvianolate injection
PK-PD model
metabolic enzymes
Lead sponsor: Xiyuan Hospital of China Academy of Chinese Medical Sciences
Sponsor class: OTHER
First posted: 2017-10-11
Enrollment: 18
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The combination of anti-platelet medicine treatment and Chinese traditional medicine (TCM) promoting blood circulation to removing blood stasis is widely used in treatment for cardiovascular disease. However, the material foundation, effective mechanism and drug-drug interaction is still not clear. In order to solve the puzzle of rational use of Joint application by TCM and Western Medicine(WM),investigators conduct a research on mechanism of drug-drug interaction between salvianolate injection and aspirin based on metabolic enzyme and PK-PD model. This clinical trial contain three groups, aspirin group, salvianolate injection group and combination (salvianolate injection+aspirin) group. Investigators collect blood samples at special time points during post-administration.Investigators have already find out the Salvianolate's pharmacokinetic characteristics in vivo and establish the biological sample-testing analysis method in previous research. Depending on these results, this clinical trial aim to explore the pharmacodynamics-pharmacokinetics(PK-PD) characteristics of combination with Salvianolate and aspirin through biomarkers, blood concentration. Finally clarify the TCM and WM material basis and mutual mechanism of drug interaction and guide reasonable clinical prescription.


Eligibility criteria: Inclusion Criteria:

1. Meet the diagnostic criteria of coronary heart disease.
2. Meet the diagnostic criteria of stable angina pectoris.
3. Meet the diagnostic criteria of syndrome of blood stasis.
4. Angina in grade I-II according to Canadian cardiovascular society (CCS).
5. It could be enrolled if the subject taking aspirin or salvianolate injection with one month regularly。
6. The subjects were informed and voluntarily signed informed consent.

Exclusion Criteria:

1. Severe heart disease (acute myocardial infarction of acute myocardial infarction in 6 months), severe cardiopulmonary dysfunction (eg: cardiac function II)
2. Poorly controlled hypertension(systolic pressure \>160mmHg or diastolic pressure \>100mmHg).
3. Diabetics.
4. Severe primary diseases such as liver and renal hematopoietic system damage. Such as:liver function（ALT≥2×ULN、AST≥2×ULN）,kidney function（Cr\>1.0×ULN) or nervous and mental disorder.
5. Pregnant, breast-feeding and menstrual women, or women planning pregnancy within 3 months.
6. Subjects who participated in clinical trials in recent 3 months.
7. Subjects who took surgery treatment or had hemorrhagic tendency in recent 4 weeks.
8. Subjects who had drug allergy history or with allergic constitution.
9. Subjects who has mental or physical disorders.
10. Subjects who had bad compliance or is not suitable for this clinical trial by investigator's judgement

Primary outcomes:
measure: Change of P-selection expression(platelet activation-dependent granule membrane) at different time points.
timeFrame: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
measure: Change of PAC-1 expression (platelet-associated complement) on the activated platelets at different time points.
timeFrame: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
measure: Change of P2Y12 acceptor expression on platelets at different time points. (P2Y12 acceptor is a receptor for ADP(adenosine diphosphate) and ATP (adenosine triphosphate )coupled to G-proteins that inhibit the adenylyl cyclase second messenger system)
timeFrame: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
measure: Change of PDE enzymes（phosphodiesterase）expression on platelet at different time points.
timeFrame: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
Secondary outcomes:
measure: Change of Aspirin esterase activity at different blood concentration of Asprin/Salvianolate
timeFrame: Getting blood sample before taking aspirin in day 8 and day 9.In the day 10, getting blood sample before taking aspirin and after taking aspirin in 5min、15min、30min、45min、1h、2h、4h、8h、12h、24h
measure: Change of Catechol-o-methyltransferase (COMT) activity at different blood concentration of Asprin/Salvianolate
timeFrame: Getting blood sample before injection in day 8 and day 9.In the day 10, getting blood sample before injection and after injection in 5min、15min、30min、45min、1h、2h、4h、8h、12h、24h
Other outcomes:
Locations:
Study officials:
References:
citation: Cao W, Yang Q, Zhang W, Xu Y, Wang S, Wu Y, Zhao Y, Guo Z, Li R, Gao R. Drug-drug interactions between salvianolate injection and aspirin based on their metabolic enzymes. Biomed Pharmacother. 2021 Mar;135:111203. doi: 10.1016/j.biopha.2020.111203. Epub 2021 Jan 3.
citation: Zhang W, Zhu B, Cao W, Li R, Wang S, Gao R. Research on the mechanism of drug-drug interaction between salvianolate injection and aspirin based on the metabolic enzyme and PK-PD model: study protocol for a PK-PD trial. Trials. 2018 Sep 14;19(1):491. doi: 10.1186/s13063-018-2861-7.