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Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin

Primary Purpose

Angina, Stable

Status

Unknown status

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

salvianolate injection

Aspirin Tablet

About this trial

This is an interventional treatment trial for Angina, Stable focused on measuring drug-drug interaction, Asprin, salvianolate injection, PK-PD model, metabolic enzymes

Eligibility Criteria

35 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Severe heart disease (acute myocardial infarction of acute myocardial infarction in 6 months), severe cardiopulmonary dysfunction (eg: cardiac function II)
Poorly controlled hypertension(systolic pressure >160mmHg or diastolic pressure >100mmHg).
Diabetics.
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.
Pregnant, breast-feeding and menstrual women, or women planning pregnancy within 3 months.
Subjects who participated in clinical trials in recent 3 months.
Subjects who took surgery treatment or had hemorrhagic tendency in recent 4 weeks.
Subjects who had drug allergy history or with allergic constitution.
Subjects who has mental or physical disorders.
Subjects who had bad compliance or is not suitable for this clinical trial by investigator's judgement

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

aspirin arm

salvianolate injection arm

aspirin and salvianolate injection arm

Arm Description

only take aspirin (100mg,qd) orally for 10 days treatment course

only inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course

take aspirin (100mg,qd) orally and inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course

Outcomes

Primary Outcome Measures

Change of P-selection expression(platelet activation-dependent granule membrane) at different time points.

Use flow cytometric method to detect the P-selection expression on platelet at different time points. Analyse the influence of Asprin/Salvianolate on platelet interaction adhesion during drug concentration-time curves.

Change of PAC-1 expression (platelet-associated complement) on the activated platelets at different time points.

Use flow cytometric method to detect the PAC-1 expression on platelet at different time points. Analyse the influence of Asprin/Salvianolate on platelet aggregation during drug concentration-time curves.

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)

Use flow cytometric method to detect the P2Y12 acceptor expression on platelet at different time points. Analyse the influence of Asprin/Salvianolate on platelets aggregation activated by ADP or ATP during drug concentration-time curves.

Change of PDE enzymes（phosphodiesterase）expression on platelet at different time points.

Use ELISA method to detect the PDE enzymes expression at different time points. Analyse the influence of Asprin/Salvianolate on platelets activated by PDE enzymes during drug concentration-time curves.

Secondary Outcome Measures

Change of Aspirin esterase activity at different blood concentration of Asprin/Salvianolate

Conduct biological analysis by LC-MS/MS(liquid chromatography tandem mass spectrometry) to detect Aspirin and salicylic aspirin and salicylic acid:CSA/C(ASA+SA).The activity of combination arm and of the asprin arm is compared by t test.

Change of Catechol-o-methyltransferase (COMT) activity at different blood concentration of Asprin/Salvianolate

COMT activity is the main metabolic enzymes of SAB.Use kit to detect COMT activity .

Full Information

NCT ID

NCT03306550

First Posted

September 4, 2017

Last Updated

October 9, 2017

Sponsor

Xiyuan Hospital of China Academy of Chinese Medical Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03306550

Brief Title

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

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Unknown status

Study Start Date

October 10, 2017 (Anticipated)

Primary Completion Date

April 10, 2018 (Anticipated)

Study Completion Date

October 10, 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Xiyuan Hospital of China Academy of Chinese Medical Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Angina, Stable

Keywords

drug-drug interaction, Asprin, salvianolate injection, PK-PD model, metabolic enzymes

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

aspirin arm

Arm Type

Active Comparator

Arm Description

only take aspirin (100mg,qd) orally for 10 days treatment course

Arm Title

salvianolate injection arm

Arm Type

Active Comparator

Arm Description

only inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course

Arm Title

aspirin and salvianolate injection arm

Arm Type

Experimental

Arm Description

take aspirin (100mg,qd) orally and inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course

Intervention Type

Drug

Intervention Name(s)

salvianolate injection

Intervention Description

The main ingredient of salvianolate injection is salvianolic acid B(SAB) which is extracted from the root of red salvia. Red salvia is used in traditional Chinese Medicine. It could promote blood circulation to removing blood stasis,which is clinically effective in treatment for cardiovascular disease.

Intervention Type

Drug

Intervention Name(s)

Aspirin Tablet

Intervention Description

Anti-platelet medicine treatment and Chinese traditional medicine (TCM) promoting blood circulation to removing blood stasis is widely used in treatment for cardiovascular disease.

Primary Outcome Measure Information:

Title

Change of P-selection expression(platelet activation-dependent granule membrane) at different time points.

Description

Time Frame

Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h

Title

Change of PAC-1 expression (platelet-associated complement) on the activated platelets at different time points.

Description

Time Frame

Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h

Title

Description

Time Frame

Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h

Title

Change of PDE enzymes（phosphodiesterase）expression on platelet at different time points.

Description

Time Frame

Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h

Secondary Outcome Measure Information:

Title

Change of Aspirin esterase activity at different blood concentration of Asprin/Salvianolate

Description

Time Frame

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

Title

Change of Catechol-o-methyltransferase (COMT) activity at different blood concentration of Asprin/Salvianolate

Description

COMT activity is the main metabolic enzymes of SAB.Use kit to detect COMT activity .

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

35 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Meet the diagnostic criteria of coronary heart disease. Meet the diagnostic criteria of stable angina pectoris. Meet the diagnostic criteria of syndrome of blood stasis. Angina in grade I-II according to Canadian cardiovascular society (CCS). It could be enrolled if the subject taking aspirin or salvianolate injection with one month regularly。 The subjects were informed and voluntarily signed informed consent. Exclusion Criteria: Severe heart disease (acute myocardial infarction of acute myocardial infarction in 6 months), severe cardiopulmonary dysfunction (eg: cardiac function II) Poorly controlled hypertension(systolic pressure >160mmHg or diastolic pressure >100mmHg). Diabetics. 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. Pregnant, breast-feeding and menstrual women, or women planning pregnancy within 3 months. Subjects who participated in clinical trials in recent 3 months. Subjects who took surgery treatment or had hemorrhagic tendency in recent 4 weeks. Subjects who had drug allergy history or with allergic constitution. Subjects who has mental or physical disorders. Subjects who had bad compliance or is not suitable for this clinical trial by investigator's judgement

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Rui Li, MD,Phd

Phone

0086+01062835651

crystal005@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

wantong Zhang, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

33401223

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.

Results Reference

derived

PubMed Identifier

30217228

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.

Results Reference

derived

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Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin

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