ACCEL-LOADING-ACS Study

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

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).

Study Overview

• Status: Completed
• Conditions: Myocardial Reperfusion Injury; Platelet Aggregation Inhibitors; Anti-inflammatory Agent
• Intervention / Treatment: Drug: Dual Anti-Platelet Therapy (DAPT); Drug: Triple Anti-Platelet Therapy (TAPT)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonsangnam-do
    • Jinju, Gyeonsangnam-do, Korea, Republic of, 660-702
      • Gyeonsang National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DAPT	Drug: Dual Anti-Platelet Therapy (DAPT); Loading: aspirin 300mg + clopidogrel 600mg; Maintenance: aspirin 200mg/d + clopidogrel 75mg/d for 1 month
Experimental: TAPT	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular events (MACE)	Composite of cardiac death, MI and ischemia-driven target lesion revascularization (TLR)	1 month

Secondary Outcome Measures

Outcome Measure	Time Frame
P2Y12 reaction unit levels in the 2 arms	1 month
MACE incidence according to P2Y12 reaction unit	1 month
any post-procedural increase of markers of myocardial injury above ULN	1 month
post-procedural variations from baseline of hs-CRP levels in the 2 arms	1 month
ACUITY major/minor bleeding rate	1 month
24hr post-procedural variations from baseline of inflammation markers (IL-6, TNF-alpha, cell adhesion molecules (VCAM, ICAM, E-selectin)	1 month

Collaborators and Investigators

• Sponsor: Gyeongsang National University Hospital
• Investigators: Principal Investigator: Kyounghoon Lee, MD, PhD, Gil Hospital; Principal Investigator: Jae-Hyeong Park, MD, PhD, Chungnam National University Hospital; Principal Investigator: Keun-Ho Park, MD, Heart Center of Chonnam National University Hospital; Principal Investigator: Jon Suh, MD, PhD, Soon Chun Hyang University; Principal Investigator: Sang-Yong Yoo, MD, PhD, Gangneung Asan Medical Center

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: May 15, 2011
• First Submitted That Met QC Criteria: May 16, 2011
• First Posted (Estimate): May 17, 2011

Study Record Updates

• Last Update Posted (Estimate): September 24, 2013
• Last Update Submitted That Met QC Criteria: September 23, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Inflammation; Platelet; Myonecrosis; Cilostazol
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Cardiomyopathies; Reperfusion Injury; Myocardial Reperfusion Injury
• Other Study ID Numbers: ACCEL-LOADING