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Impaired renal function is associated with reduced responsiveness to clopidogrel. There are no studies which have shown a means by which to overcome platelet hyporesponsiveness in patients with chronic kidney disease (CKD). The purpose of this study was to determine the functional impact of cilostazol in patients with CKD undergoing hemodialysis.
The aims of this study is to evaluate the effects of platelet responsiveness to clopidogrel or cilostazol in CKD patients undergoing hemodialysis. The differences in platelet activation markers are also evaluated before and after clopidogrel or cilostazol administration. The investigators will perform a prospective, randomized study to compare the degree of platelet inhibition and platelet activation markers by adjunctive cilostazol (100 mg twice daily) compared to clopidogrel (75 or 150 mg/day) in CKD patients undergoing hemodialysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| clopidogrel 75 mg/day | Active Comparator | CKD patients undergoing chronic hemodialysis and PCI for stable coronary artery disease will be randomized to receive clopidogrel 75 mg/day for 14 days. |
|
| clopidogrel 150 mg/day | Active Comparator | CKD patients undergoing chronic hemodialysis and PCI for stable coronary artery disease will be randomized to receive clopidogrel 150 mg/day for 14 days. |
|
| adjunctive cilostazol | Active Comparator | CKD patients undergoing chronic hemodialysis and PCI for stable coronary artery disease will be randomized to receive co-administration of adjunctive cilostazol (100 mg twice daily) and clopidogrel (75 mg/day; [group 3, 20 patients]) for 14 days. |
|
| 75mg clopidogrel | Active Comparator | control group undergoing PCI for stable angina will be also maintained on clopidogrel (75 mg/day for 14 days). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clopidogrel, cilostazol | Drug | Patients with CKD received clopidogrel (75 mg/day)for 14 days Patients with CKD received clopidogrel (150 mg/day)for 14 days Patients with CKD received clopidogrel (75 mg/day)and cilostazol (100 mg twice daily)for 14 days 75mg clopidogrel in patients with normal kidney function for 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| The differences of platelet aggregation according to the anti-platelet therapy. | Platelet function was assessed with light transmittance aggregometry and the VerifyNowTM P2Y12 assay. High on-treatment platelet reactivity was defined as 5 μmol/L of ADP-induced Aggmax > 50%. Inhibition of platelet aggregation (IPA) was defined as the percent decrease in aggregation values obtained at baseline and after treatment. VerifyNow-P2Y12 assay results are also assessed and expressed in P2Y12 reaction units (PRUs) and the percentage of inhibition. | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Changes of platelet activation markers according to the anti-platelet therapy | Markers of platelet activation (soluble CD40 ligand [sCD40L] and soluble P-selectin [sP-selectin]) were assessed at baseline and after 14 days of anti-platelet therapy. | 14 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Weon Kim, MD, PhD | Kyunghee University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kyung Hee University | Seoul | 130-702 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19840579 | Result | Park SH, Kim W, Park CS, Kang WY, Hwang SH, Kim W. A comparison of clopidogrel responsiveness in patients with versus without chronic renal failure. Am J Cardiol. 2009 Nov 1;104(9):1292-5. doi: 10.1016/j.amjcard.2009.06.049. | |
| 17261652 | Result | Angiolillo DJ, Shoemaker SB, Desai B, Yuan H, Charlton RK, Bernardo E, Zenni MM, Guzman LA, Bass TA, Costa MA. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study. Circulation. 2007 Feb 13;115(6):708-16. doi: 10.1161/CIRCULATIONAHA.106.667741. Epub 2007 Jan 29. |
| Label | URL |
|---|---|
| Korea Food and Drug Administration | View source |
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| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D060050 | Angina, Stable |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D000077144 | Clopidogrel |
| D000077407 | Cilostazol |
| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
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|
|
| 20223369 | Result | Angiolillo DJ, Bernardo E, Capodanno D, Vivas D, Sabate M, Ferreiro JL, Ueno M, Jimenez-Quevedo P, Alfonso F, Bass TA, Macaya C, Fernandez-Ortiz A. Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy. J Am Coll Cardiol. 2010 Mar 16;55(11):1139-46. doi: 10.1016/j.jacc.2009.10.043. |
| 35224730 | Derived | Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4. |
| 22137075 | Derived | Woo JS, Kim W, Lee SR, Jung KH, Kim WS, Lew JH, Lee TW, Lim CK. Platelet reactivity in patients with chronic kidney disease receiving adjunctive cilostazol compared with a high-maintenance dose of clopidogrel: results of the effect of platelet inhibition according to clopidogrel dose in patients with chronic kidney disease (PIANO-2 CKD) randomized study. Am Heart J. 2011 Dec;162(6):1018-25. doi: 10.1016/j.ahj.2011.09.003. Epub 2011 Nov 8. |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000787 | Angina Pectoris |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D002637 | Chest Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D011804 | Quinolines |