The Dynamic Effect of Non-cytochrome P450 Isoenzyme 3A4（CYP3A4）-Metabolized and Cytochrome P450 Isoenzyme 3A4（CYP3A4）-Metabolized Statins on Clopidogrel Resistance in Patients With Cerebral Infarction

Cerebral Infarction Clinical Trial

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02411903
• Other study ID #: H0906
• Status: Enrolling by invitation
• Phase: Phase 4
• First received: March 17, 2015
• Last updated: June 14, 2015
• Start date: March 2015
• Est. completion date: August 2016

Study information

• Verified date: April 2015
• Source: The Third Affiliated Hospital of Guangzhou Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The investigators team had found that the presence of dynamic changes of Clopidogrel resistance are not associated with genetic factors. Currently, study on moderate doses of statins and dynamic Clopidogrel resistance has not been reported, therefore this study will observe 160 cases of open prospective secondary prevention in patients with cerebral infarction. Excluded: those patients occurs Clopidogrel resistance because of slow metabolism caused by cytochrome P450 isoenzyme 2C19（CYP2C19, and then observed the impact of the cytochrome P450 isoenzyme 3A4 （CYP3A4）-metabolized and non-cytochrome P450 isoenzyme 3A4 （CYP3A4）—metabolized statins dynamically on Clopidogrel resistance in the next 9 months, adverse events will be recorded, the metabolite of clopidogrel（H4 ）and the polymorphism of cytochrome P450 isoenzyme 2C19 （CYP2C19）/cytochrome P450 isoenzyme 3A4 （CYP3A4）/ cytochrome P450 isoenzyme 2C9（CYP2C9）will be detected. Expected Result: the patients use the cytochrome P450 isoenzyme 3A4（CYP3A4）-metabolized statins will result in dynamic Clopidogrel resistance easily ,H4 levels will decline, and Clopidogrel resistance is not related to the polymorphism of cytochrome P450 isoenzyme 3A4 （CYP3A4）.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 160
• Est. completion date: August 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 85 Years

Eligibility

Inclusion Criteria:

• The patient must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

• Age <85 years and >45 years ,Male or female.

• The patient have been Cerebral infarction for one month.

• national institutes of health stroke scale(NIHSS)score =23 points.

• Blood Platelet count greater than 150×10^9/L,and Less than 500×10^9/L.

• The patient never do not taking aspirin ?dipyridamole?clopidogrel,or the patient had been taken these anti-platelet drugs but has been discontinued for two weeks at least.

• The patient never do not taking Statins or the patient have been stop taking statins 2 weeks for two weeks.

Exclusion Criteria:

• Allergic constitution , or allergic to the composition of the drugs in this study.

• national institutes of health stroke scale(NIHSS) score >23 points.

• Atrial fibrillation and other cardiogenic cerebral embolism.

• Patients who were undergone surgery and trauma (including fractures) within the past three month.

• Patients with known dysfunction of vital organs or suffered from Serious cardiovascular disease ,or coagulation disorders.

• The patient took Proton pump inhibitors recently.

• The history of data collection and the follow-up process can not be saved.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebral Infarction
• Clopidogrel,Poor Metabolism of (Disorder)
• Infarction

Intervention

Drug:
• atorvastatin and clopidogrel
Dose: atorvastatin 40mg/d plus clopidogrel 75mg/d for 9 months.
• rosuvastatin and clopidogrel
Dose: rosuvastatin 20mg/d plus clopidogrel 75mg/d for 9 months.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The Third Affiliated Hospital of Guangzhou Medical University

References & Publications (3)

Lev EI, Patel RT, Maresh KJ, Guthikonda S, Granada J, DeLao T, Bray PF, Kleiman NS. Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J Am Coll Cardiol. 2006 Jan 3;47(1):27-3 — View Citation

Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol. 2005 Apr 19;45(8):1157-64. Review. — View Citation

Sugunaraj JP, Palaniswamy C, Selvaraj DR, Chaitanya Arudra SK, Sukhija R. Clopidogrel resistance. Am J Ther. 2010 Mar-Apr;17(2):210-5. doi: 10.1097/MJT.0b013e3181bdc3e4. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence of clopidogrel resistance	Definition of clopidogrel resistance is the absolute change of 5 microliter adenosine diphosphate(ADP) induced PAR=10% as compared to baseline. So, incidence of clopidogrel resistance= (PAR at monitor point - PAR at baseline) / PAR at baseline×100 %=10 %? Measures of PAR: PAR is measured by Light transmittance aggregometry (LTA) and according to the standard of Rev?	For nine months	No