ACCEL-LOADING-ACS Study

Myocardial Reperfusion Injury Clinical Trial

Official title:

ACCELerated Inhibition of Platelet Aggregation, Inflammation and Ischemia-reperfusion Injury by Adjunctive Cilostazol Loading in Patients With Acute Coronary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01354808
• Other study ID #: ACCEL-LOADING
• Status: Completed
• Phase: Phase 4
• First received: May 15, 2011
• Last updated: September 23, 2013
• Start date: July 2010

Study information

• Verified date: September 2013
• Source: Gyeongsang National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether adjunctive cilostazol loading/maintenance to standard treatment (aspirin, clopidogrel, and statin) is effective in reduction of major adverse cardiovascular events, platelet activation, inflammation and myonecrosis in patients with non-ST-elevation acute coronary syndrome (ACS)undergoing percutaneous coronary intervention (PCI).

Description:

In ACS patients, platelet activation, inflammation, and ischemia-reperfusion injury can be closely associated with the risk of post-PCI myonecrosis and ischemic events occurrence. In the ACCEL-AMI (Adjunctive Cilostazol versus high maintenance-dose ClopidogrEL in patients with Acute Myocardial Infarction)study, adjunctive cilostazol increased platelet inhibition compared with double-dose clopidogrel. Meanwhile, statins can reduce the extent of myonecrosis via limiting inflammation and myocardial infarct size by activating phosphatidylinositol-3-kinase (PI3K), ecto-5'-nucleotidase, Akt/endothelial nitric oxide synthase (eNOS), and the downstream effectors inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Inhibition of PI3K, adenosine receptors, eNOS, iNOS, or COX-2 abrogates the protective effects of statins. In animal study, the combination of low-dose statin with cilostazol synergistically limits infarct size. Multiple studies have shown that cilostazol can influence inflammation and RISK pathway using the similar pathway with statin. This study will be performed to evaluate the role of adjunctive cilostazol in platelet inhibition, inflammation, and myonecrosis compared with standard treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• at least 18 years of age

• Non-ST-elevation ACS patients undergoing PCI within 48 hours after hospitalization

Exclusion Criteria:

• ST segment elevation acute myocardial infarction

• NSTE ACS with high-risk features warranting emergency coronary angiography

• Oral anticoagulation therapy with warfarin

• Use of pre-procedural glycoprotein IIb/IIIa inhibitor

• Contraindication to antiplatelet therapy

• AST or ALT = 3 times upper normal

• Left ventricular ejection fraction < 30%

• WBC < 3,000/mm3, platelet < 100,000/mm3

• Creatinine = 3 mg/dl

• stroke within 3 months

Study Design

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

Related Conditions & MeSH terms

• Anti-inflammatory Agent
• Myocardial Reperfusion Injury
• Platelet Aggregation Inhibitors
• Reperfusion Injury

Intervention

Drug:
• Dual Anti-Platelet Therapy (DAPT)
Loading: aspirin 300mg + clopidogrel 600mg Maintenance: aspirin 200mg/d + clopidogrel 75mg/d for 1 month
• Triple Anti-Platelet Therapy (TAPT)
Loading: cilostazol 200mg + aspirin 300mg + clopidogrel 600mg Maintenance: cilostazol 100mg bid+ aspirin 200mg/d+ clopidogrel 75mg/d for 1 month

Locations

Country	Name	City	State
Korea, Republic of	Gyeonsang National University Hospital	Jinju	Gyeonsangnam-do

Sponsors (1)

Lead Sponsor	Collaborator
Gyeongsang National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (2)

Jeong YH, Hwang JY, Kim IS, Park Y, Hwang SJ, Lee SW, Kwak CH, Park SW. Adding cilostazol to dual antiplatelet therapy achieves greater platelet inhibition than high maintenance dose clopidogrel in patients with acute myocardial infarction: Results of the — View Citation

Patti G, Pasceri V, Colonna G, Miglionico M, Fischetti D, Sardella G, Montinaro A, Di Sciascio G. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARM — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major adverse cardiovascular events (MACE)	Composite of cardiac death, MI and ischemia-driven target lesion revascularization (TLR)	1 month	No
Secondary	P2Y12 reaction unit levels in the 2 arms		1 month	Yes
Secondary	MACE incidence according to P2Y12 reaction unit		1 month	Yes
Secondary	any post-procedural increase of markers of myocardial injury above ULN		1 month	No
Secondary	post-procedural variations from baseline of hs-CRP levels in the 2 arms		1 month	No
Secondary	ACUITY major/minor bleeding rate		1 month	Yes
Secondary	24hr post-procedural variations from baseline of inflammation markers (IL-6, TNF-alpha, cell adhesion molecules (VCAM, ICAM, E-selectin)		1 month	No