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Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin

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ClinicalTrials.gov Identifier: NCT03306550
Recruitment Status : Not yet recruiting
First Posted : October 11, 2017
Last Update Posted : October 11, 2017
Sponsor:
Information provided by (Responsible Party):
Xiyuan Hospital of China Academy of Chinese Medical Sciences

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.

Condition or disease Intervention/treatment Phase
Angina, Stable Drug: salvianolate injection Drug: Aspirin Tablet Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Research on Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin Based on the Metabolic Enzyme and PK-PD Model
Estimated Study Start Date : October 10, 2017
Estimated Primary Completion Date : April 10, 2018
Estimated Study Completion Date : October 10, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions
Drug Information available for: Aspirin

Arm Intervention/treatment
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: 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.

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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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 .



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Ages Eligible for Study:   35 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03306550


Contacts
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Contact: Rui Li, MD,Phd 0086+01062835651 crystal005@163.com
Contact: wantong Zhang, MD

Sponsors and Collaborators
Xiyuan Hospital of China Academy of Chinese Medical Sciences

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Xiyuan Hospital of China Academy of Chinese Medical Sciences
ClinicalTrials.gov Identifier: NCT03306550     History of Changes
Other Study ID Numbers: zz0908022
First Posted: October 11, 2017    Key Record Dates
Last Update Posted: October 11, 2017
Last Verified: August 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xiyuan Hospital of China Academy of Chinese Medical Sciences:
drug-drug interaction
Asprin
salvianolate injection
PK-PD model
metabolic enzymes

Additional relevant MeSH terms:
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Aspirin
Angina, Stable
Angina Pectoris
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics