Clinical trial NCT01609647: Reloading Prasugrel or Clopidogrel on High Platelet Reactivity Before Percutaneous Coronary Intervention
Official title: Comparison of Prasugrel and Clopidogrel Reloading on High Platelet Reactivity in Clopidogrel-loaded Patients Undergoing Percutaneous Coronary Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Coronary Syndrome
Keywords: High plate reactivity unit after loading dose of clopidogrel
Lead sponsor: Dong-A University
Sponsor class: OTHER
First posted: 2012-06-01
Enrollment: 76
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: High platelet reactivity unit (PRU) after loading dose clopidogrel in patients undergoing percutaneous coronary intervention (PCI) is related to high risk of short and long term recurrent ischemic events including stent thrombosis.

The investigators hypothesize that additional loading of prasugrel in patients with high PRU after clopidogrel loading would be superior to additional loading of clopidogrel in reducing platelet reactivity and thereby result in lower risk of short term recurrent ischemic events.

Detailed description: Dual antiplatelet therapy with acetylsalicyclic acid (ASA) and additional clopidogrel is now standard regimen for the prevention of recurrent ischemic events in patients who undergo PCI.

But decreased effect of clopidogrel in a group of patients was reported and they are known to be associated with high risk of recurrent ischemic event. Decreased effect of clopidogrel is mainly resulted from decreased function to metabolite prodrug, clopidogrel to active form of drug.

Prasugrel, newer thienopyridine has been recently developed and showed advantages to clopidogrel. Prasugrel is known to have shorter onset time to achieve steady state level than clopidogrel and constant pharmacologic effect regardless of patient diversity.

High PRU after loading dose clopidogrel in patients undergoing PCI is known to be related to increased risk of short and long term recurrent ischemic events including stent thrombosis. Prasugrel has been reported to be effective in reducing platelet reactivity in patients showing resistance to clopidogrel and high PRU.

The investigators hypothesize that additional loading of prasugrel in patients with high PRU after clopidogrel loading would be superior to additional loading of clopidogrel in reducing platelet reactivity and thereby result in reduced risk of short term recurrent ischemic events.

The investigators plan to include 70 acute coronary syndrome patients who are planned to undergo PCI and show high platelet reactivity. Most patients with ACS administer loading dose of ASA and clopidogrel as soon as they are assumed to be ACS.

The investigators plan to perform platelet reactivity test by VeryfyNow (VN) before PCI and enroll patients with high PRU defined by 235 or more. They are to randomly administered additional 300mg of clopidogrel or 20mg of prasugrel.

Eligibility criteria: Inclusion Criteria:

* Acute coronary syndrome
* Patients planned to undergo percutaneous transluminal coronary angioplasty
* Patients who agreed to the experimental plan which was permitted by IRB

Exclusion Criteria:

* Low body weight (\<50kg)
* Urgent PCI for ACS
* Use of glycoprotein IIb/IIIa inhibitor in recent 24hrs or planned to
* History of transient ischemic attack
* History of upper gastrointestinal bleeding in recent 6 months
* Renal dysfunction defined as serum creatinine \> 2.5 mg/dl
* Severe hepatic dysfunction defined as serum transaminase \> 3 times normal limit
* Bleeding tendency
* Anticoagulation treatment including warfarin
* Thrombocytopenia defined by platelet \< 100,000/ml
* Anemia defined by hemoglobin \< 10 g/dl
* Contraindication for study drugs

Primary outcomes:
measure: HPR at 24 hours
timeFrame: 24 hours
Secondary outcomes:
measure: MACE
timeFrame: 30 days (1 month)
measure: Bleeding
timeFrame: 30 days (1 month)
measure: HPRs
timeFrame: 4 hours after PCI, 30 days after PCI
measure: Periprocedural myocardial infarction
timeFrame: 48 hours after PCI
measure: Periprocedural myocardial injury
timeFrame: 48 hours after PCI
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: DongA University Hospital
Study officials:
affiliation: Director, Regional Clinical Trial Center
name: Moo Hyun Kim, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Guo LZ, Kim MH, Shin ES, Ann SH, De Jin C, Cho YR, Park JS, Park K, Park TH, Lee MS, Serebruany VL. Thienopyridine reloading in clopidogrel-loaded patients undergoing percutaneous coronary interventions: The PRAISE study. Int J Cardiol. 2016 Nov 1;222:639-644. doi: 10.1016/j.ijcard.2016.08.027. Epub 2016 Aug 4.
citation: Lee DH, Kim MH, Park TH, Park JS, Park K, Zhang HZ, Seo JM, Lee MS. Comparison of prasugrel and clopidogrel reloading on high platelet reactivity in clopidogrel-loaded patients undergoing percutaneous coronary intervention (PRAISE-HPR): a study protocol for a prospective randomized controlled clinical trial. Trials. 2013 Feb 28;14:62. doi: 10.1186/1745-6215-14-62.