OPTImal Management of Antithrombotic Agents: OPTIMA-5

Study Overview
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Brief Summary
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This is a prospective, randomized, open-label clinical trial which will enroll 80 acute coronary syndrome (ACS) patients after Percutaneous Transluminal Coronary Intervention (PCI) in China. Patients on maintenance dosing (MD) of aspirin (100 mg/d) and ticagrelor (90 mg twice daily) will be divided into two groups switching from ongoing ticagrelor to clopidogrel 600 mg loading dose (LD)/ 75 mg MD according to their bleeding risk. Then each group will randomly switch at different times(24 hours/ 12 hours after the last MD of ticagrelor). Pharmacodynamic assessments are performed at baseline, and at 4h, 8h, 24h, 48h, 72h hours with platelet aggregation rate by Light Transmittance Aggregometry method (LTA). All patients are followed-up for 30 days.

Detailed Description
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The primary endpoint of the study was platelet inhibition measured by Light Transmittance Aggregometry method(LTA). Secondary clinical endpoints included a 30-day major adverse cardiovascular endpoint (MACE) defined as a composite of cardiovascular death, recurrent myocardial infarction, target vessel revascularisation or stroke and individual components of the MACE. Safety endpoints of 30-day TIMI major and minor bleed were also evaluated.

Official Title
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A Randomized Controlled Trial on the Switch From Ticagrelor to Clopidogrel in Acute Coronary Syndrome Patients After Percutaneous Coronary Intervention--OPTImal Management of Antithrombotic Agents: OPTIMA-5

Conditions
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Acute Coronary Syndrome (ACS)

Intervention / Treatment
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* Drug: Switch ticagrelor to clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years. ACS patients. Patients who are treated with ticagrelor and do not tolerate it. Volunteer to participate and sign informed consent. Approved by national regulatory authorities ethics committees. Exclusion Criteria: Patients who are contraindicated, intolerant or resistant to clopidogrel. History of hematological disease or bleeding tendency; platelet count < 100 × 10^9 cells/L, or > 600 × 10^9 cells/L, hemoglobin < 100 g/L. Abnormal liver or kidney function (ALT > 3 ULN; estimated CrCl < 30 ml/min calculated by Cockcroft-Gault equation); diagnosed severe pulmonary disease. Patients in need of drugs which affect the efficacy of clopidogrel such as miconazole, ketoconazole, andfluconazole. Malignancies or other comorbid conditions with life expectancy less than 1 year. Pregnant or lactating woman.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: clopidogrel-600 mg-12h<br>clopidogrel 600 mg loading dose (LD) 12 hours after the last maintenance dose（MD） of ticagrelor followed by 75 mg MD daily | Drug: Switch ticagrelor to clopidogrel<br>* Switch ticagrelor to clopidogrel with 600 mg loading dose (LD)/75 mg maintenance dose（MD）12/24 hours after the last MD of ticagrelor<br>* Other names: switch;|
| Experimental: clopidogrel-600 mg-24h<br>clopidogrel 600 mg loading dose (LD) 24 hours after the last maintenance dose（MD） of ticagrelor followed by 75 mg MD daily | Drug: Switch ticagrelor to clopidogrel<br>* Switch ticagrelor to clopidogrel with 600 mg loading dose (LD)/75 mg maintenance dose（MD）12/24 hours after the last MD of ticagrelor<br>* Other names: switch;|
| Experimental: clopidogrel-75 mg-12h<br>clopidogrel 75 mg maintenance dose(MD) 12 hours after the last MD of ticagrelor | Drug: Switch ticagrelor to clopidogrel<br>* Switch ticagrelor to clopidogrel with 600 mg loading dose (LD)/75 mg maintenance dose（MD）12/24 hours after the last MD of ticagrelor<br>* Other names: switch;|
| Experimental: clopidogrel-75 mg-24h<br>clopidogrel 75 mg maintenance dose（MD) 24 hours after the last MD of ticagrelor | Drug: Switch ticagrelor to clopidogrel<br>* Switch ticagrelor to clopidogrel with 600 mg loading dose (LD)/75 mg maintenance dose（MD）12/24 hours after the last MD of ticagrelor<br>* Other names: switch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of platelet aggregation between different time points | Regional differences between blood samples from each subjects of different groups by LTA.The results of LTA are reported in platelet aggregation rate(%).Platelet aggregation was induced by0.5mg/ml arachidonic acid (AA). | baseline,4 hours,8 hours,24 hours,48 hours,72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of clinical endpoint event | Secondary clinical endpoints included a 30-day major adverse cardiovascular endpoint (MACE) defined as a composite of cardiovascular death, recurrent myocardial infarction, target vessel revascularisation or stroke and individual components of the MACE. Safety endpoints of 30-day TIMI major and minor bleed were also evaluated. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dual antiplatelet therapy (DAPT), Platelet function, Clopidogrel, Ticagrelor, Switch