Aspirin Impact on Platelet Reactivity in Acute Coronary Syndrome Patients on Novel P2Y12 Inhibitors Therapy

Acute Coronary Syndrome Clinical Trial

Official title:

Aspirin Impact on Platelet Reactivity in Acute Coronary Syndrome Patients on Novel P2Y12 Inhibitors Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02049762
• Other study ID #: 0813-13-SMC
• Status: Completed
• Phase: Phase 4
• First received: January 28, 2014
• Last updated: February 19, 2018
• Start date: June 2015
• Est. completion date: January 2017

Study information

• Verified date: February 2018
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Thus far, no study has evaluated the impact on aspirin in addition to the newer and more potent P2Y12 inhibitors, among ACS patients and current guidelines recommend dual anti-platelet therapy consisting of aspirin and a novel P2Y12 inhibitor in this population.

Objective The investigators goal is to examine the effect of aspirin in addition to new anti-platelet agent (ticagrelor\prasugrel) on platelet reactivity in comparison with placebo, among ACS patients treated percutaneously.

Design The proposed study is a randomized-controlled, double blind trial, conducted among ACS patients treated percutaneously. Eligible patients will recruited during hospitalization due to ACS after percutaneous coronary intervention (PCI), and randomization by envelopes on 1:1 basis will take place a month after the index event, at a follow-up visit at the cardiac clinic.

Platelet function and Endothelial function tests will be taken a month after the index event, and at a 2 weeks periods following aspirin/placebo therapy, cross-over and return to open-label aspirin.

End-points platelet function tests will be compared between aspirin and placebo therapy and before and after the cross-over.

Description:

Introduction:

Current knowledge and data support the use of dual anti-platelets for patients after acute coronary syndrome (ACS). Novel P2Y12 inhibitors have shown their superiority on clopidogrel in regarding morbidity and mortality, but at the cost of higher bleeding rates - even in lower doses of aspirin there is increase risk for gastrointestinal (GI) bleeding. In a geographical analysis of the PLATO trial it has been shown difference at outcome. When higher dose of aspirin were used, the superiority of ticagrelor was reduced.

The use of platelet reactivity tests have been proved and acknowledged in their usefulness for gauging bleeding and ischemic risks. Few studies have shown that clopidogral is inhibiting not only the ADP activity, but also the arachidonic acid (AA) pathway that is considered aspirin specific pathway. Examining the effect of potent P2Y12 inhibitors in healthy volunteers have shown increased inhibition of the AA pathway. Not only that the adding of aspirin, have shown little effect on inhibition of AA pathway.

It has been demonstrated that vascular endothelial function is inversely correlated to platelet reactivity in both individuals without established cardiovascular disease (controls) and acute myocardial infarction patients.

Objective Our goal is to examine the effect (platelet function test and endothelial function) of aspirin while added to novel P2Y12 inhibitors treated ACS patients.

Design The proposed study is a randomized-controlled, double blind trial, conducted among ACS patients treated percutaneously. Eligible patients will recruited during hospitalization due to ACS after percutaneous coronary intervention (PCI), and randomization by envelopes on 1:1 basis will take place a month after the index event, at a follow-up visit at the cardiac clinic.

Platelet function and Endothelial function tests will be taken a month after the index event, and at a 2 weeks periods following aspirin/placebo therapy, cross-over and return to open-label aspirin.

Study end-points The primary end-point is platelet function tests in response to AA. Secondary end-points will include endothelial function and platelet reactivity according to the platelet activity and VerifyNow test in response to ADP and platelet activation Clinical outcomes including all-cause and cardiac mortality and hospitalizations, recurrent ischemia and stent thrombosis, and bleeding events along with blood transfusions, will be recorded as safety end-points.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age>18 years

• ACS defined according to the 3rd universal definition of MI

• PCI therapy

Exclusion Criteria:

• Indication for anticoagulant therapy

• ACS on new P2Y12 inhibitors treatment

• Contraindication to P2Y12 therapy

• Renal failure defined as creatinine =1.5 mg/dL

• Non-compliance

• Life-threatening extra-cardiac disease or malignancy with a life expectancy below 1 year

• Inability to sign an informed consent

• Participation in another trial during the previous 6 months

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Novel P2Y12 Inhibitors
• Platelet Function and Reactivity Tests
• Syndrome

Intervention

Drug:
• Aspirin
Aspirin 100 mg vs. placebo in ACS patients on P2Y12 inhibitors a month following PCI.

Locations

Country	Name	City	State
Israel	Sheba Medical Center	Tel-Hashomer

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (14)

Armstrong PC, Dhanji AR, Tucker AT, Mitchell JA, Warner TD. Reduction of platelet thromboxane A2 production ex vivo and in vivo by clopidogrel therapy. J Thromb Haemost. 2010 Mar;8(3):613-5. doi: 10.1111/j.1538-7836.2009.03714.x. Epub 2009 Dec 3. — View Citation

Armstrong PC, Leadbeater PD, Chan MV, Kirkby NS, Jakubowski JA, Mitchell JA, Warner TD. In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation. J Thromb Haemost. 2011 Mar;9(3):552-61. doi: 10.1111/j.1538-7836.2010.04160.x. — View Citation

Hallas J, Dall M, Andries A, Andersen BS, Aalykke C, Hansen JM, Andersen M, Lassen AT. Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMJ. 2006 Oct 7;333(7571):726. Epub 2006 Sep 19. — View Citation

Hobson AR, Qureshi Z, Banks P, Curzen NP. Effects of clopidogrel on "aspirin specific" pathways of platelet inhibition. Platelets. 2009 Sep;20(6):386-90. — View Citation

Kirkby NS, Leadbeater PD, Chan MV, Nylander S, Mitchell JA, Warner TD. Antiplatelet effects of aspirin vary with level of P2Y12 receptor blockade supplied by either ticagrelor or prasugrel. J Thromb Haemost. 2011 Oct;9(10):2103-5. doi: 10.1111/j.1538-7836.2011.04453.x. — View Citation

Lanas A, García-Rodríguez LA, Arroyo MT, Gomollón F, Feu F, González-Pérez A, Zapata E, Bástida G, Rodrigo L, Santolaria S, Güell M, de Argila CM, Quintero E, Borda F, Piqué JM; Asociación Española de Gastroenterología. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut. 2006 Dec;55(12):1731-8. Epub 2006 May 10. — View Citation

Mahaffey KW, Wojdyla DM, Carroll K, Becker RC, Storey RF, Angiolillo DJ, Held C, Cannon CP, James S, Pieper KS, Horrow J, Harrington RA, Wallentin L; PLATO Investigators. Ticagrelor compared with clopidogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 2011 Aug 2;124(5):544-54. doi: 10.1161/CIRCULATIONAHA.111.047498. Epub 2011 Jun 27. — View Citation

Roy P, Bonello L, Torguson R, de Labriolle A, Lemesle G, Slottow TL, Steinberg DH, Kaneshige K, Xue Z, Satler LF, Kent KM, Suddath WO, Pichard AD, Lindsay J, Waksman R. Impact of "nuisance" bleeding on clopidogrel compliance in patients undergoing intracoronary drug-eluting stent implantation. Am J Cardiol. 2008 Dec 15;102(12):1614-7. doi: 10.1016/j.amjcard.2008.07.063. Epub 2008 Sep 27. — View Citation

Tantry US, Bonello L, Aradi D, Price MJ, Jeong YH, Angiolillo DJ, Stone GW, Curzen N, Geisler T, Ten Berg J, Kirtane A, Siller-Matula J, Mahla E, Becker RC, Bhatt DL, Waksman R, Rao SV, Alexopoulos D, Marcucci R, Reny JL, Trenk D, Sibbing D, Gurbel PA; Working Group on On-Treatment Platelet Reactivity. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013 Dec 17;62(24):2261-73. doi: 10.1016/j.jacc.2013.07.101. Epub 2013 Sep 27. — View Citation

Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30. — View Citation

Wang TY, Xiao L, Alexander KP, Rao SV, Kosiborod MN, Rumsfeld JS, Spertus JA, Peterson ED. Antiplatelet therapy use after discharge among acute myocardial infarction patients with in-hospital bleeding. Circulation. 2008 Nov 18;118(21):2139-45. doi: 10.1161/CIRCULATIONAHA.108.787143. Epub 2008 Nov 3. — View Citation

Warner TD, Armstrong PC, Curzen NP, Mitchell JA. Dual antiplatelet therapy in cardiovascular disease: does aspirin increase clinical risk in the presence of potent P2Y12 receptor antagonists? Heart. 2010 Nov;96(21):1693-4. doi: 10.1136/hrt.2010.205724. — View Citation

Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. Epub 2007 Nov 4. — View Citation

Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16;345(7):494-502. Erratum in: N Engl J Med 2001 Nov 15;345(20):1506. N Engl J Med 2001 Dec 6;345(23):1716. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	clinical outcome	hospitalizations and mortality	two months
Primary	Platelet reactivity	platelet reactivity in response to arachidonic acid	one month
Secondary	platelet reactivity	platelet reactivity in response to ADP	one month