Reloading Prasugrel or Clopidogrel on High Platelet Reactivity Before Percutaneous Coronary Intervention

Acute Coronary Syndrome Clinical Trial

— PRAISE-HPR  

Official title:

Comparison of Prasugrel and Clopidogrel Reloading on High Platelet Reactivity in Clopidogrel-loaded Patients Undergoing Percutaneous Coronary Intervention

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01609647
• Other study ID #: PRAISE-HPR
• Status: Completed
• Phase: Phase 3
• First received: May 29, 2012
• Last updated: December 21, 2014
• Start date: September 2012
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: Dong-A University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Coronary Syndrome

Intervention

Drug:
• Prasugrel
Reloading with prasugrel 20mg and followed by daily administration of prasugrel 5mg for 30 days
• Clopidogrel
Reloading with clopidogrel 300mg and followed by daily administration of clopidogrel 75mg for 30 days

Locations

Country	Name	City	State
Korea, Republic of	DongA University Hospital	Busan

Sponsors (1)

Lead Sponsor	Collaborator
Dong-A University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HPR at 24 hours	Persistently high platelet reactivity after PCI. PRU is measured by methods of VerifyNow device and HPRU is defined as PRU of 240 or more.	24 hours	No
Secondary	MACE	Major adverse cardiovascular events consist of cardiac death, myocardial infarction, stroke, stent thrombosis, cardiac enzyme (CRP, CK-MB, Troponin-I)	30 days (1 month)	Yes
Secondary	Bleeding	Major, minor or minimal bleeding defined by TIMI(thrombolysis in myocardial infarction) bleeding criteria	30 days (1 month)	No
Secondary	HPRs	Persistently high platelet reactivity 4 hours and 30 days after PCI. PRU is measured by methods of VerifyNow device and HPRU is defined as PRU of 240 or more.	4 hours after PCI, 30 days after PCI	No
Secondary	Periprocedural myocardial infarction	Cardiac troponin value is >5x99th percentile upper reference plus either (1) evidence of prolonged ischaemic chest pain (>20min) or (2) ischaemic ST changes or new pathological Q waves, or (3) angiographic evidence of a side branch occlusion, slow-flow or no-reflow, embolization, or (4) imaging evidence of new regional wall motion abnormality.	48 hours after PCI	Yes
Secondary	Periprocedural myocardial injury	Cardiac troponin (cTn) value is =5x99th percentile upper reference limit (URL) after PCI and cTn value was normal before the PCI or cTn value is >5x99th percentile URL in absence of ischaemic chest pain or ST changes, with normal angiographic and imaging findings.	48 hours after PCI	Yes