Clinical trial NCT03062462: Half-dose Ticagrelor Overcomes High-dose Clopidogrel in Acute Coronary Syndrome Patients With High On-Clopidogrel Platelet Reactivity
Official title: Half-dose Ticagrelor Overcomes High-dose Clopidogrel in Acute Coronary Syndrome Patients With High On-Clopidogrel Platelet Reactivity
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Coronary Artery Disease
Clopidogrel, Poor Metabolism of
Lead sponsor: First Affiliated Hospital of Harbin Medical University
Sponsor class: OTHER
First posted: 2017-02-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: With the widespread use of clopidogrel, resistance to clopidogrel has been attracting increasing attention, and emerged as a new challenge adversely affecting patients clinical risk and outcome. Clopidogrel resistance means that blood platelets show little or no response to clopidogrel. It is closely associated with increased risk of serious cardiovascular events, seriously affects the prognosis of patients, and brings difficulties to clinical treatment.

Guideline recommendations on the use of dual antiplatelet therapy have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular events. The previous studies have reported that half-dose ticagrelor had the similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was significantly stronger than that in the clopidogrel group. But it is still not very clear that the effect of low-dose ticagrelor on platelet function in patients with clopidogrel resistance and coronary heart disease.

Therefore, we performed this randomized, single-blind clinical trial to observe the effects of low-dose ticagrelor and double standard-dose clopidogrel on platelet aggregation and prognosis in clopidogrel resistance's patients with coronary heart disease.

Detailed description: Dual Antiplatelet Therapy (DAPT) with aspirin and P2Y12 receptor inhibitor remains a cornerstone in the secondary prevention of coronary artery disease (CAD). Clopidogrel is one of the most commonly used antithrombotic agent that inhibits the platelet P2Y(12) adenosine diphosphate (ADP) receptor. With the widespread use of clopidogrel, resistance to clopidogrel has been attracting increasing attention, and emerged as a new challenge adversely affecting patients clinical risk and outcome. Clopidogrel resistance means that blood platelets show little or no response to clopidogrel. Recent studies have found that clopidogrel resistance rate was about 11% \~ 44%. Clopidogrel resistance is more common in patients with loss-of-function CYP2C19 genotypes, and closely associated with increased risk of serious cardiovascular events, including ischemic events, myocardial infarction, stent thrombosis, revascularization and so on. This seriously affects the prognosis of patients, and brings difficulties to clinical treatment.

Ticagrelor is an oral, reversibly-binding, direct-acting P2Y12 receptor antagonist used clinically for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS). Guideline recommendations on the use of dual antiplatelet therapy have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular events. The previous studies have reported that half-dose ticagrelor had the similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was significantly stronger than that in the clopidogrel group. But it is still not very clear that the effect of low-dose ticagrelor on platelet function in patients with clopidogrel resistance and coronary heart disease.

Therefore, we performed this randomized, single-blind clinical trial to observe the effects of low-dose ticagrelor and double standard-dose clopidogrel on platelet aggregation and cardiovascular prognosis in clopidogrel resistance's patients with coronary heart disease.

Eligibility criteria: Inclusion Criteria:

1. Patients with oral clopidogrel treatment admitted to hospital within 24 hours or long-term follow-up outpatients with oral clopidogrel treatment;
2. The platelet aggregation rate (PAgR) measured with light transmission aggregometry (LTA) is decreased no more than 10% from baseline level, or PAgR is more than 46% and the percentage of inhibition of ADP-induced platelet aggregation measured by thrombelastogram is not more than 30%;

Exclusion Criteria:

1. Planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, or anticoagulant therapy during the study period;
2. Platelet count \<100g/L;
3. Creatinine clearance rate \< 30ml/min;
4. Diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive heart failure NYHA II-IV or left ventricular ejection fraction \< 40%);
5. A history of bleeding tendency;
6. Aspirin, ticagrelor or clopidogrel allergies;
7. Severe liver injury.

Primary outcomes:
measure: The platelet aggregation rate
timeFrame: up to 7 days
Secondary outcomes:
measure: Side effects including bleeding,dyspnea and arrhythmia
timeFrame: up to 7 days, 1 month, 3 months, 6 months and 12 months
measure: Adverse events including myocardial infarction, death, stroke, re-hospitalization for cardiovascular diseases and ischemia events
timeFrame: up to 7 days, 1 month, 3 months, 6 months and 12 months
Other outcomes:
Locations:
city: Havertown
country: United States
facility: whole blood lumi-aggregometer type 560 VS
state: Pennsylvania
Study officials:
References:
citation: Liu GZ, Zhang S, Sun DH, Shi J, Bo WL, Wang WN, Zhang CY, Wang ZH, Feng W, He MJ, Liu YY, Li S, Zheng LQ, Li Y. Half-dose ticagrelor versus high-dose clopidogrel in reducing platelet reactivity in acute coronary syndrome patients with high on-clopidogrel platelet reactivity (divide study). Eur J Clin Pharmacol. 2019 Aug;75(8):1059-1068. doi: 10.1007/s00228-019-02687-0. Epub 2019 May 12.