Angina, StableNCT03306550
Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin
A study testing salvianolate injection and Aspirin Tablet in people with Angina, Stable, run by Xiyuan Hospital of China Academy of Chinese Medical Sciences.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 65 years
- Conditions the study is for
- Angina, Stable
- What is being tested?
- salvianolate injection and Aspirin Tablet
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- 10 Oct 2017to 10 Oct 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
No sites are listed yet.
wantong Zhang, MD contact
About this study
Official title: 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.
- Conditions
- Angina, Stable
- Being tested
- salvianolate injection, Aspirin Tablet
- Keywords
- drug-drug interaction, Asprin, salvianolate injection, PK-PD model, metabolic enzymes
- Medical subject headings
- Angina, Stable
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
salvianolate injectionDrug
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.
Aspirin TabletDrug
Anti-platelet medicine treatment and Chinese traditional medicine (TCM) promoting blood circulation to removing blood stasis is widely used in treatment for cardiovascular disease.
| Study group | Role | What they receive |
|---|---|---|
| aspirin arm | Active comparator | only take aspirin (100mg,qd) orally for 10 days treatment course Receives: Drug: Aspirin Tablet |
| salvianolate injection arm | Active comparator | only inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course Receives: Drug: salvianolate injection |
| aspirin and salvianolate injection arm | Experimental | take aspirin (100mg,qd) orally and inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course Receives: Drug: salvianolate injection; Drug: Aspirin Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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)
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.
Measured: 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.
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.
Measured: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
Secondary outcomes (2)
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.
Measured: 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
COMT activity is the main metabolic enzymes of SAB.Use kit to detect COMT activity .
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2017
- Study start10 Oct 2017 (estimated)
- Primary completion10 Apr 2018 (estimated)
- Study completion10 Oct 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Angina, StableStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiyuan Hospital of China Academy of Chinese Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03306550
- Sponsor's protocol ID
- zz0908022
- Status last verified
- Aug 2017
- First submitted
- 4 Sep 2017
- Last updated
- 11 Oct 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33401223Zhang 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.
PubMed 30217228
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Research on Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin Based on the Metabolic Enzyme and PK-PD Model
- ClinicalTrials.gov ID
- NCT03306550
- Acronym / sponsor ID
- zz0908022
- Conditions
- Angina, Stable
- Keywords
- drug-drug interaction, Asprin, salvianolate injection, PK-PD model, metabolic enzymes
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Xiyuan Hospital of China Academy of Chinese Medical SciencesUniversity, hospital or other
- Study start
- 10 Oct 2017 (estimated)
- Primary completion
- 10 Apr 2018 (estimated)
- Study completion
- 10 Oct 2018 (estimated)
- First posted
- 11 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| aspirin arm | Active comparator | Drug: Aspirin Tabletonly take aspirin (100mg,qd) orally for 10 days treatment course |
| salvianolate injection arm | Active comparator | Drug: salvianolate injectiononly inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course |
| aspirin and salvianolate injection arm | Experimental | Drug: salvianolate injection, Drug: Aspirin Tablettake aspirin (100mg,qd) orally and inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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。
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| salvianolate injectionThe 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. | Drug | aspirin and salvianolate injection arm, salvianolate injection arm |
| Aspirin TabletAnti-platelet medicine treatment and Chinese traditional medicine (TCM) promoting blood circulation to removing blood stasis is widely used in treatment for cardiovascular disease. | Drug | aspirin and salvianolate injection arm, aspirin arm |
Primary outcome
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.
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.
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.
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.
2 secondary outcomes
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2017.
- Derived from this study: PubMed 33401223Cao 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.
- Derived from this study: PubMed 30217228Zhang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
wantong Zhang, MD contact
Questions about this trial
What is this clinical trial studying?
A study testing salvianolate injection and Aspirin Tablet in people with Angina, Stable, run by Xiyuan Hospital of China Academy of Chinese Medical Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rui Li, MD,Phd (0086+01062835651, crystal005@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03306550, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2017.