Reversal of the Anti-platelet Effects of Ticagrelor

NCT02383771 | Completed Phase 4

• 1 other identifier: 003
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the proportion of untreated donor platelets required to fully reverse the platelet inhibitory effects of ticagrelor and aspirin in healthy persons and patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) and receiving ticagrelor.

Conditions

Coronary Artery Disease

Keywords

Ticagrelor; Aspirin; Peri-operative treatment

Outcome Measures

Primary Outcomes (2)

• Reversal of the platelet inhibitory effects of antiplatelet therapy in healthy volunteers

  Proportion of untreated donor platelets required to fully reverse the platelet inhibitory effects of antiplatelet therapy

  7 days after randomization

• Reversal of the platelet inhibitory effects of antiplatelet therapy in patients

  Reversal of the platelet inhibitory effects of antiplatelet therapy Proportion of untreated donor platelets required to fully reverse the platelet inhibitory effects of antiplatelet therapy in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) and receiving ticagrelor

  7 days after percutaneous coronary intervention

Secondary Outcomes (2)

• Inhibition of platelet aggregation in response to AA or ADP

  7 days after randomization

• Change of ADP-induced platelet aggregation in platelets saved in blood bank due to the saving time

  5 days after fresh platelet collected and stored in blood bank

Study Arms (4)

Single Anti-platelet Treatment

EXPERIMENTAL

Ticagrelor

Drug: Ticagrelor

Dual Anti-platelet Treatment

EXPERIMENTAL

Aspirin + Ticagrelor

Drug: Aspirin + Ticagrelor

Control

SHAM COMPARATOR

No Drug

Drug: Control

CAD undergoing PCI

OTHER

Patients with coronary artery disease undergoing percutaneous coronary intervention and receiving dual anti-platelet therapy (ticagrelor 90mg bid + aspirin 100mg daily)

Drug: Aspirin + Ticagrelor

Interventions

Ticagrelor DRUG

(Ticagrelor 90mg Bid) x 7days

Also known as: Brilinta

Single Anti-platelet Treatment

Aspirin + Ticagrelor DRUG

(Aspirin 100mg daily + Ticagrelor 90mg Bid) x 7days

Also known as: Brilinta

Dual Anti-platelet Treatment

Control DRUG

No Anti-platelet Therapy

Control

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers;
• Subjects aged \>18 years old;

You may not qualify if:

• Allergy or intolerance to aspirin or ticagrelor;
• Subjects at a high risk of bleeding (e.g. platelet count\<100×10\^9/L, history of peptic ulcer, hemoglobin\<110g/L);
• Subjects with anemia;
• Subjects with bronchial asthma or chronic obstructive pulmonary disease;
• Subjects with bradycardia (e.g. sick sinus syndrome, high-grade atrioventricular block, history of syncope with unproved uncorrelation with bradycardia);
• Smokers;
• Subjects with diabetes mellitus;
• Subjects planning to be pregnancy;
• Subjects with hepatic or renal dysfunction;
• Subjects who have taken other anti-platelet drugs, non-steroidal anti-inflammatory drugs or proton pump inhibitors before scanning or need to take them during study period.
• Cohort 2:
• Subjects with diagnosed coronary artery disease undergoing percutaneous coronary intervention (PCI);
• Subjects who have received dual anti-platelet therapy (ticagrelor 90mg bid + aspirin 100mg daily) for 7 days;
• Subjects at a high risk of bleeding (e.g. platelet count\<100×10\^9/L, history of peptic ulcer, hemoglobin\<110g/L);
• Subjects with anemia;

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• National Natural Science Foundation of China: collaborator

Study Sites (1)

First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029, China

Location

Related Publications (17)

• Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, Copland I, Fox KA; Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001 Aug 18;358(9281):527-33. doi: 10.1016/s0140-6736(01)05701-4.

  PMID: 11520521 BACKGROUND

• Kushner FG, Hand M, Smith SC Jr, King SB 3rd, Anderson JL, Antman EM, Bailey SR, Bates ER, Blankenship JC, Casey DE Jr, Green LA, Hochman JS, Jacobs AK, Krumholz HM, Morrison DA, Ornato JP, Pearle DL, Peterson ED, Sloan MA, Whitlow PL, Williams DO. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009 Dec 1;54(23):2205-41. doi: 10.1016/j.jacc.2009.10.015. No abstract available.

  PMID: 19942100 BACKGROUND

• Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol. 2005 Apr 19;45(8):1157-64. doi: 10.1016/j.jacc.2005.01.034.

  PMID: 15837243 BACKGROUND

• Trenk D, Hochholzer W, Fromm MF, Chialda LE, Pahl A, Valina CM, Stratz C, Schmiebusch P, Bestehorn HP, Buttner HJ, Neumann FJ. Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J Am Coll Cardiol. 2008 May 20;51(20):1925-34. doi: 10.1016/j.jacc.2007.12.056.

  PMID: 18482659 BACKGROUND

• Ellis KJ, Stouffer GA, McLeod HL, Lee CR. Clopidogrel pharmacogenomics and risk of inadequate platelet inhibition: US FDA recommendations. Pharmacogenomics. 2009 Nov;10(11):1799-817. doi: 10.2217/pgs.09.143.

  PMID: 19891556 BACKGROUND

• Chong AY, So DY. Ticagrelor for the treatment of peripheral arterial disease. Expert Opin Investig Drugs. 2014 Dec;23(12):1737-43. doi: 10.1517/13543784.2014.974803. Epub 2014 Nov 6.

  PMID: 25376000 BACKGROUND

• Solbeck S, Meyer MA, Johansson PI, Meyer AS, Cotton BA, Stensballe J, Schott U, Ostrowski SR. Monitoring of dabigatran anticoagulation and its reversal in vitro by thrombelastography. Int J Cardiol. 2014 Oct 20;176(3):794-9. doi: 10.1016/j.ijcard.2014.07.084. Epub 2014 Aug 4.

  PMID: 25156858 BACKGROUND

• Montalescot G, van 't Hof AW, Lapostolle F, Silvain J, Lassen JF, Bolognese L, Cantor WJ, Cequier A, Chettibi M, Goodman SG, Hammett CJ, Huber K, Janzon M, Merkely B, Storey RF, Zeymer U, Stibbe O, Ecollan P, Heutz WM, Swahn E, Collet JP, Willems FF, Baradat C, Licour M, Tsatsaris A, Vicaut E, Hamm CW; ATLANTIC Investigators. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med. 2014 Sep 11;371(11):1016-27. doi: 10.1056/NEJMoa1407024. Epub 2014 Sep 1.

  PMID: 25175921 BACKGROUND

• Gurbel PA, Antonino MJ, Tantry US. Recent developments in clopidogrel pharmacology and their relation to clinical outcomes. Expert Opin Drug Metab Toxicol. 2009 Aug;5(8):989-1004. doi: 10.1517/17425250903107772.

  PMID: 19575629 BACKGROUND

• Cannon CP, Harrington RA, James S, Ardissino D, Becker RC, Emanuelsson H, Husted S, Katus H, Keltai M, Khurmi NS, Kontny F, Lewis BS, Steg PG, Storey RF, Wojdyla D, Wallentin L; PLATelet inhibition and patient Outcomes Investigators. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet. 2010 Jan 23;375(9711):283-93. doi: 10.1016/S0140-6736(09)62191-7. Epub 2010 Jan 13.

  PMID: 20079528 BACKGROUND

• Li C, Hirsh J, Sloane D, Liang Y, Bai J, Paikin J, Johnston MA, DeBeer J, Eikelboom JW. Aspirin response variability after major orthopedic surgery. Thromb Res. 2012 Aug;130(2):216-20. doi: 10.1016/j.thromres.2012.04.006. Epub 2012 May 9.

  PMID: 22575418 BACKGROUND

• Teng R, Butler K. Pharmacokinetics, pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y(12) receptor antagonist, in healthy subjects. Eur J Clin Pharmacol. 2010 May;66(5):487-96. doi: 10.1007/s00228-009-0778-5. Epub 2010 Jan 21.

  PMID: 20091161 BACKGROUND

• Li C, Hirsh J, Xie C, Johnston MA, Eikelboom JW. Reversal of the anti-platelet effects of aspirin and clopidogrel. J Thromb Haemost. 2012 Apr;10(4):521-8. doi: 10.1111/j.1538-7836.2012.04641.x.

  PMID: 22268852 BACKGROUND

• Hobl EL, Derhaschnig U, Firbas C, Schoergenhofer C, Schwameis M, Jilma B. Reversal strategy in antagonizing the P2Y12 -inhibitor ticagrelor. Eur J Clin Invest. 2013 Dec;43(12):1258-61. doi: 10.1111/eci.12168. Epub 2013 Sep 23.

  PMID: 24112116 BACKGROUND

• Storey RF, Bliden KP, Ecob R, Karunakaran A, Butler K, Wei C, Tantry U, Gurbel PA. Earlier recovery of platelet function after discontinuation of treatment with ticagrelor compared with clopidogrel in patients with high antiplatelet responses. J Thromb Haemost. 2011 Sep;9(9):1730-7. doi: 10.1111/j.1538-7836.2011.04419.x.

  PMID: 21707911 BACKGROUND

• Coelho MJ, Monteiro Tde C, Vasquez FG, Silva KL, Dos Santos KS, de Oliveira VM, Cavalcante Fde O. Platelet aggregation and quality control of platelet concentrates produced in the Amazon Blood Bank. Rev Bras Hematol Hemoter. 2011;33(2):110-4. doi: 10.5581/1516-8484.20110030.

  PMID: 23284257 BACKGROUND

• Shams Hakimi C, Hesse C, Wallen H, Boulund F, Grahn A, Jeppsson A. In vitro assessment of platelet concentrates with multiple electrode aggregometry. Platelets. 2015;26(2):132-7. doi: 10.3109/09537104.2014.898141. Epub 2014 Jul 7.

  PMID: 24999542 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Ticagrelor; Aspirin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Chunjian Li, Ph.D

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: March 9, 2015
• Study Start: March 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: August 16, 2017

Record last verified: 2017-08

Locations

CN (1)