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

NCT02983214 | Completed Phase 4 DMC

• 1 other identifier: Cilo-UoI-2016
• Study Type: interventional
• Target: 826
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ischemic Stroke; Peripheral Artery Disease; Diabetes Mellitus, Type 2

Keywords

Cilostazol; Clopidogrel; Peripheral Artery Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  12 months

Secondary Outcomes (2)

• Number of participants whose major secondary efficacy end point desribed in the description section is observed.

  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.

  12 months

Study Arms (2)

Clopidogrel

ACTIVE COMPARATOR

Clopidogrel 75 mg/day

Drug: Clopidogrel

Clopidogrel plus cilostazol

ACTIVE COMPARATOR

Clopidogrel 75 mg/day plus cilostazol 100 mg twice/day

Drug: Clopidogrel; Drug: Cilostazol

Interventions

Clopidogrel DRUG

Also known as: Plavix, Clodelib, Clovelen

Clopidogrel; Clopidogrel plus cilostazol

Cilostazol DRUG

Also known as: Claudiasil

Clopidogrel plus cilostazol

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Ioannina: lead
• LIBYTEC Pharmaceutical S.A.: collaborator

Study Sites (1)

Atherothrombosis Research Centre / Laboratory of Biochemistry, University of Ioannina

Ioannina, Epirus, 45110, Greece

Location

Related Publications (16)

• Kalantzi KI, Tsoumani ME, Goudevenos IA, Tselepis AD. Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives. Expert Rev Clin Pharmacol. 2012 May;5(3):319-36. doi: 10.1586/ecp.12.19.

  PMID: 22697594 BACKGROUND

• Dindyal S, Kyriakides C. A review of cilostazol, a phosphodiesterase inhibitor, and its role in preventing both coronary and peripheral arterial restenosis following endovascular therapy. Recent Pat Cardiovasc Drug Discov. 2009 Jan;4(1):6-14. doi: 10.2174/157489009787260025.

  PMID: 19149700 BACKGROUND

• Jeong YH, Tantry US, Bliden KP, Gurbel PA. Cilostazol to overcome high on-treatment platelet reactivity in korean patients treated with clopidogrel and calcium-channel blocker. Circ J. 2011;75(11):2534-6. doi: 10.1253/circj.cj-11-1076. Epub 2011 Oct 5. No abstract available.

  PMID: 21970840 BACKGROUND

• Rizzo M, Corrado E, Patti AM, Rini GB, Mikhailidis DP. Cilostazol and atherogenic dyslipidemia: a clinically relevant effect? Expert Opin Pharmacother. 2011 Mar;12(4):647-55. doi: 10.1517/14656566.2011.557359. Epub 2011 Feb 2.

  PMID: 21284580 BACKGROUND

• Liu Y, Fong M, Cone J, Wang S, Yoshitake M, Kambayashi J. Inhibition of adenosine uptake and augmentation of ischemia-induced increase of interstitial adenosine by cilostazol, an agent to treat intermittent claudication. J Cardiovasc Pharmacol. 2000 Sep;36(3):351-60. doi: 10.1097/00005344-200009000-00011.

  PMID: 10975593 BACKGROUND

• Tselepis AD. Cilostazol-based triple antiplatelet therapy in the era of generic clopidogrel and new potent antiplatelet agents. Curr Med Res Opin. 2014 Jan;30(1):51-4. doi: 10.1185/03007995.2013.850070. Epub 2013 Oct 18. No abstract available.

  PMID: 24089998 BACKGROUND

• Chapman TM, Goa KL. Cilostazol: a review of its use in intermittent claudication. Am J Cardiovasc Drugs. 2003;3(2):117-38. doi: 10.2165/00129784-200303020-00006.

  PMID: 14727939 BACKGROUND

• Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss LK, Golzarian J, Gornik HL, Halperin JL, Jaff MR, Moneta GL, Olin JW, Stanley JC, White CJ, White JV, Zierler RE; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society for Vascular Medicine; Society for Vascular Surgery. 2011 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Peripheral Artery Disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011 Nov 1;58(19):2020-45. doi: 10.1016/j.jacc.2011.08.023. Epub 2011 Oct 6. No abstract available.

  PMID: 21963765 BACKGROUND

• Spiliopoulos S. Antiplatelet therapy in critical limb ischemia: update on clopidogrel and cilostazol. J Cardiovasc Surg (Torino). 2014 Oct;55(5):631-40. Epub 2014 May 28.

  PMID: 24866775 BACKGROUND

• Chen Y, Zhang Y, Tang Y, Huang X, Xie Y. Long-term clinical efficacy and safety of adding cilostazol to dual antiplatelet therapy for patients undergoing PCI: a meta-analysis of randomized trials with adjusted indirect comparisons. Curr Med Res Opin. 2014 Jan;30(1):37-49. doi: 10.1185/03007995.2013.850067. Epub 2013 Oct 18.

  PMID: 24083626 BACKGROUND

• Min PK, Jung JH, Ko YG, Choi D, Jang Y, Shim WH. Effect of cilostazol on in-stent neointimal hyperplasia after coronary artery stenting: a quantative coronary angiography and volumetric intravascular ultrasound study. Circ J. 2007 Nov;71(11):1685-90. doi: 10.1253/circj.71.1685.

  PMID: 17965485 BACKGROUND

• Douglas JS Jr, Holmes DR Jr, Kereiakes DJ, Grines CL, Block E, Ghazzal ZM, Morris DC, Liberman H, Parker K, Jurkovitz C, Murrah N, Foster J, Hyde P, Mancini GB, Weintraub WS; Cilostazol for Restenosis Trial (CREST) Investigators. Coronary stent restenosis in patients treated with cilostazol. Circulation. 2005 Nov 1;112(18):2826-32. doi: 10.1161/CIRCULATIONAHA.104.530097. Epub 2005 Oct 24.

  PMID: 16246948 BACKGROUND

• Kwon SU, Cho YJ, Koo JS, Bae HJ, Lee YS, Hong KS, Lee JH, Kim JS. Cilostazol prevents the progression of the symptomatic intracranial arterial stenosis: the multicenter double-blind placebo-controlled trial of cilostazol in symptomatic intracranial arterial stenosis. Stroke. 2005 Apr;36(4):782-6. doi: 10.1161/01.STR.0000157667.06542.b7. Epub 2005 Mar 3.

  PMID: 15746463 BACKGROUND

• Panagiotakos DB, Georgousopoulou EN, Pitsavos C, Chrysohoou C, Metaxa V, Georgiopoulos GA, Kalogeropoulou K, Tousoulis D, Stefanadis C; ATTICA Study group. Ten-year (2002-2012) cardiovascular disease incidence and all-cause mortality, in urban Greek population: the ATTICA Study. Int J Cardiol. 2015 Feb 1;180:178-84. doi: 10.1016/j.ijcard.2014.11.206. Epub 2014 Nov 26.

  PMID: 25463360 BACKGROUND

• Toyoda K, Uchiyama S, Hoshino H, Kimura K, Origasa H, Naritomi H, Minematsu K, Yamaguchi T; CSPS.com Study Investigators. Protocol for Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com): a randomized, open-label, parallel-group trial. Int J Stroke. 2015 Feb;10(2):253-8. doi: 10.1111/ijs.12420. Epub 2014 Dec 8.

  PMID: 25487817 BACKGROUND

• Kalantzi K, Tentolouris N, Melidonis AJ, Papadaki S, Peroulis M, Amantos KA, Andreopoulos G, Bellos GI, Boutel D, Bristianou M, Chrisis D, Dimitsikoglou NA, Doupis J, Georgopoulou C, Gkintikas SA, Iraklianou S, Kanellas Kappa, Kotsa K, Koufakis T, Kouroglou M, Koutsovasilis AG, Lanaras L, Liouri E, Lixouriotis C, Lykoudi A, Mandalaki E, Papageorgiou E, Papanas N, Rigas S, Stamatelatou MI, Triantafyllidis I, Trikkalinou A, Tsouka AN, Zacharopoulou O, Zoupas C, Tsolakis I, Tselepis AD. Efficacy and Safety of Adjunctive Cilostazol to Clopidogrel-Treated Diabetic Patients With Symptomatic Lower Extremity Artery Disease in the Prevention of Ischemic Vascular Events. J Am Heart Assoc. 2021 Jan 5;10(1):e018184. doi: 10.1161/JAHA.120.018184. Epub 2020 Dec 17.

  PMID: 33327737 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Peripheral Arterial Disease; Diabetes Mellitus, Type 2

Interventions

Clopidogrel; Cilostazol

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tetrazoles; Azoles; Quinolines

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Biochemistry and Clinical Chemistry

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 6, 2016
• Study Start: November 1, 2016
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: December 29, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)