Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin

October 9, 2017 updated by: Xiyuan Hospital of China Academy of Chinese Medical Sciences

Research on Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin Based on the Metabolic Enzyme and PK-PD Model

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: wantong Zhang, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

35 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: aspirin arm
only take aspirin (100mg,qd) orally for 10 days treatment course
Drug: Aspirin Tablet
Anti-platelet medicine treatment and Chinese traditional medicine (TCM) promoting blood circulation to removing blood stasis is widely used in treatment for cardiovascular disease.
Active Comparator: salvianolate injection arm
only inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course
Drug: salvianolate injection
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.
Experimental: aspirin and salvianolate injection arm
take aspirin (100mg,qd) orally and inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course
Drug: Aspirin Tablet
Anti-platelet medicine treatment and Chinese traditional medicine (TCM) promoting blood circulation to removing blood stasis is widely used in treatment for cardiovascular disease.
Drug: salvianolate injection
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change of P-selection expression(platelet activation-dependent granule membrane) at different time points.
Time Frame: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
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.
Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
Change of PAC-1 expression (platelet-associated complement) on the activated platelets at different time points.
Time Frame: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
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.
Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
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)
Time Frame: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
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.
Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
Change of PDE enzymes（phosphodiesterase）expression on platelet at different time points.
Time Frame: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
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.
Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change of Aspirin esterase activity at different blood concentration of Asprin/Salvianolate
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
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.
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
Change of Catechol-o-methyltransferase (COMT) activity at different blood concentration of Asprin/Salvianolate
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
COMT activity is the main metabolic enzymes of SAB.Use kit to detect COMT activity .
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Xiyuan Hospital of China Academy of Chinese Medical Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 10, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 10, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 10, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 4, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 11, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 11, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • zz0908022

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Angina, Stable

Clinical Trials on Aspirin Tablet

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings