Clinical trial NCT01354808: ACCEL-LOADING-ACS Study
Official title: ACCELerated Inhibition of Platelet Aggregation, Inflammation and Ischemia-reperfusion Injury by Adjunctive Cilostazol Loading in Patients With Acute Coronary Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Platelet Aggregation Inhibitors
Anti-inflammatory Agent
Myocardial Reperfusion Injury
Keywords: Cilostazol
Platelet
Inflammation
Myonecrosis
Lead sponsor: Gyeongsang National University Hospital
Sponsor class: OTHER
First posted: 2011-05-17
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Major adverse cardiovascular events (MACE)
timeFrame: 1 month
Secondary outcomes:
measure: P2Y12 reaction unit levels in the 2 arms
timeFrame: 1 month
measure: MACE incidence according to P2Y12 reaction unit
timeFrame: 1 month
measure: any post-procedural increase of markers of myocardial injury above ULN
timeFrame: 1 month
measure: post-procedural variations from baseline of hs-CRP levels in the 2 arms
timeFrame: 1 month
measure: ACUITY major/minor bleeding rate
timeFrame: 1 month
measure: 24hr post-procedural variations from baseline of inflammation markers (IL-6, TNF-alpha, cell adhesion molecules (VCAM, ICAM, E-selectin)
timeFrame: 1 month
Other outcomes:
Locations:
city: Jinju
country: Korea, Republic of
facility: Gyeonsang National University Hospital
state: Gyeonsangnam-do
Study officials:
affiliation: Gil hospital
name: Kyounghoon Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chungnam National University Hospital
name: Jae-Hyeong Park, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heart Center of Chonnam National University Hospital
name: Keun-Ho Park, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Soon Chun Hyang University
name: Jon Suh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gangneung Asan Medical Center
name: Sang-Yong Yoo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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 ARMYDA-ACS randomized trial. J Am Coll Cardiol. 2007 Mar 27;49(12):1272-8. doi: 10.1016/j.jacc.2007.02.025.
citation: 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 adjunctive cilostazol versus high maintenance dose clopidogrel in patients with AMI (ACCEL-AMI) study. Circ Cardiovasc Interv. 2010 Feb 1;3(1):17-26. doi: 10.1161/CIRCINTERVENTIONS.109.880179. Epub 2010 Jan 26.