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

December 26, 2020 updated by: Alexandros Tselepis, University of Ioannina

Study of the Efficacy and Safety of Cilostazol in the Prevention of Ischemic Vascular Events in Diabetic Patients With Symptomatic Peripheral Artery Disease.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

826

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
    • Epirus
      • Ioannina, Epirus, Greece, 45110
        • Atherothrombosis Research Centre / Laboratory of Biochemistry, University of Ioannina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

48 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients aged ≥50 years with DM2 and symptomatic PAD diagnosed clinically (according to Fontaine criteria, stage IIa or IIb and III) and by measuring the ΑΒΙ.

Exclusion Criteria:

  • Congestive heart failure, history of ventricular tachycardia, ventricular fibrillation or multifocal ventricular extrasystoles or QTc prolongation.
  • Patients with atrial fibrillation taking any anticoagulant therapy or patients with a history of cardioembolic ischemic stroke or hemorrhagic stroke.
  • Patients with a history (≤ 12 months) of acute coronary syndrome receiving dual antiplatelet therapy, or patients receiving monotherapy with aspirin.
  • Patients with hepatic impairment (child-Pugh staging, calibration ≥ 5) or renal impairment (creatinine clearance ≤ 30ml / min), recent peptic ulcer, a history of hypersensitivity to cilostazol, cancer patients undergoing treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Clopidogrel
Clopidogrel 75 mg/day
Drug: Clopidogrel
Other Names:
  • Plavix, Clodelib, Clovelen
Active Comparator: Clopidogrel plus cilostazol
Clopidogrel 75 mg/day plus cilostazol 100 mg twice/day
Drug: Clopidogrel
Other Names:
  • Plavix, Clodelib, Clovelen
Drug: Cilostazol
Other Names:
  • Claudiasil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 12 months
Death from vascular causes: cardiovascular or cerebrovascular
12 months
Number of participants who suffer from bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria during the entire follow-up period.
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants whose major secondary efficacy end point desribed in the description section is observed.
Time Frame: 12 months
Acute ischemic stroke / TIA, AMI, coronary stent thrombosis, PCI, coronary restenosis, death from cardiovascular causes, death from any cause, hospitalization for acute limb ischemia, lower extremity arterial revascularization, improvement of ABI and pain-free walking distance values.
12 months
Number of participants who suffer from the secondary safety end points which are palpitations, tachycardia, headache, diarrhea, urticaria, neoplasms, blood disorders, drug interruption.
Time Frame: 12 months
Blood disorders: transient thrombocytopenia, leukopenia
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Ioannina

Collaborators

LIBYTEC Pharmaceutical S.A.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2016

Primary Completion (Actual)

October 1, 2019

Study Completion (Actual)

October 1, 2019

Study Registration Dates

First Submitted

November 29, 2016

First Submitted That Met QC Criteria

December 1, 2016

First Posted (Estimate)

December 6, 2016

Study Record Updates

Last Update Posted (Actual)

December 29, 2020

Last Update Submitted That Met QC Criteria

December 26, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Cilo-UoI-2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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