Diabetic Artery Obstruction: is it Possible to Reduce Ischemic Events With Cilostazol? "DORIC"

Recruiting

Phase 4 Results N/A

Trial Description

Investigation of the clinical efficacy and safety of dual antiplatelet therapy with clopidogrel and cilostazol versus clopidogrel alone in preventing ischemic vascular events in patients with type 2 diabetes and symptomatic peripheral arterial disease.

Detailed Description

Cilostazol is a quinoline derivative that selectively and reversibly inhibits cellular cyclic adenosine monophosphate (cAMP) phosphodiesterase III, thus suppressing cAMP degradation and maintaining its high intracellular levels. Through this mechanism, cilostazol inhibits platelet aggregation, exerting significant antiplatelet and antithrombotic activity. Cilostazol also improves endothelial function and exerts anti-inflammatory, anti-atherogenic and vasodilatory effects. Additionally, cilostazol inhibits equilibrative nucleoside transporter-1 (ENT-1) which is responsible for the cellular uptake of adenosine, reducing its plasma concentration. Through this mechanism, cilostazol maintains high extracellular adenosine concentration allowing adenosine to exert its biological effects. Thus, cilostazol not only shows potent antithrombotic activity, but also prevents restenosis after percutaneous coronary intervention (PCI). Finally, cilostazol has beneficial effects in the lipidemic profile reducing triglyceride levels and increasing HDL-cholesterol. Clinical studies have shown that in patients with intermittent claudication, cilostazol increases the walking distance. Based on these studies, cilostazol administration in combination with an antiplatelet drug (clopidogrel or aspirin) is recommended for patients with intertermittent claudication.
Recent pharmacodynamic studies have demonstrated that adding cilostazol to aspirin or clopidogrel may represent an effective way to overcome high on-treatment platelet reactivity. Additionally, clinical studies have shown that the addition of cilostazol to dual antiplatelet therapy with aspirin and clopidogrel (triple antiplatelet therapy, TAPT) in patients with acute coronary syndrome undergoing PCI offers significant clinical benefit. This favorable effect of cilostazol was confirmed in a recent meta-analysis which included nine studies and a total of 2,179 patients undergoing PCI. Furthermore, other clinical studies have shown that administration of TAPT with cilostazol reduces restenosis after PCI. Finally, the administration of dual antiplatelet therapy with cilostazol and aspirin significantly reduces the progression of symptomatic intracranial arterial stenosis compared to monotherapy with aspirin.
The aim of The Diabetic artery Obstruction: is it possible to Reduce Ischemic events with Cilostazol? (DORIC) trial is to investigate the clinical efficacy and safety of dual antiplatelet therapy (DAPT) with clopidogrel and cilostazol versus clopidogrel alone in preventing ischemic vascular eventsin patients with type 2 diabetes (DM2) and symptomatic peripheral arterial disease (PAD).

Conditions

Interventions

  • Clopidogrel (Plavix┬«)Drug
    Other Names: Plavix
    ARM 1: Kind: Experimental
    Label: Clopidogrel
    Description: Clopidogrel 75 mg/day
    ARM 2: Kind: Experimental
    Label: Clopidogrel plus cilostazol
    Description: Clopidogrel 75 mg/day plus cilostazol 100 mg twice/day
  • Cilostazol (Pletal┬«)Drug
    Other Names: Claudiasil
    ARM 1: Kind: Experimental
    Label: Clopidogrel plus cilostazol
    Description: Clopidogrel 75 mg/day plus cilostazol 100 mg twice/day

Outcomes

Type Measure Time Frame Safety Issue
Primary Number of participants who suffer from the primary efficacy end point which is composite of acute ischemic stroke/transient ischemic attack (TIA), myocardial infarction (MI), or death from vascular causes during the entire follow-up period. 12 months
Primary Number of participants who suffer from bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria during the entire follow-up period. 12 months
Secondary Number of participants whose major secondary efficacy end point which is the free walking distance or the ankle brachial index (ABI) value will be improved during the entire follow-up period. 12 months
Secondary Number of participants who suffer from the secondary safety end points which are palpitations, tachycardia, tachyarrhythmia, hypotension, headache, nausea, diarrhea, blood disorders, drug interruption. 12 months

Sponsors