Ticagrelor Monotherapy Compared to Aspirin Monotherapy in Patients With History of ACS

NCT03881943 | Completed Phase 4 DMC

• 1 other identifier: FMD_1.3
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Antiplatelet agents are cornerstones for management of ischemic heart disease. For patients suffering from acute coronary syndrome (heart attack), treatment with aspirin and ticagrelor are typically given for one year after index heart attack and then patients will continue to take aspirin lifelong. However, these patients are still having increased risk of suffering from another heart attack. Recently data showed that adding ticagrelor to aspirin in the long term can decrease the chance of recurrent heart attack but at the cost of increased risk of major bleeding. On the other hand, ticagrelor is a potent antiplatelet agent and has been showed to have additional benefit on blood vessels and platelets. The investigator hypothesize that monotherapy with ticagrelor may have further benefit over monotherapy with aspirin in the long term management in patients with history of heart attack. The investigator plan to perform a randomized study to compare the outcome in patients taking either ticagrelor or aspirin. The primary endpoint is measurement of endothelial function by flow mediated dilatation of brachial artery which is a surrogate marker of adverse cardiovascular outcome 3 months after treatment. The investigator would also investigate secondary endpoints of patients' blood level of adenosine activity, platelet function, endothelial progenitor cell count and biomarkers

Conditions

Acute Coronary Syndrome

Outcome Measures

Primary Outcomes (1)

• Endothelial Function

  the flow mediated dilatation of brachial artery at baseline and 3 months after randomization. Demonstrate brachial diameters, the measurement will be presented in absolute FMD millimeter (FMDmm). The report value should be present in FMD percentage (FMD%) as the mean of baseline measurement minus the mean of 3 months measurement then divided by the 3 months measurement.

  3 months

Secondary Outcomes (1)

• Plasma adenosine level Platelet function parameters Endothelial progenitor cell count Biomarkers such as highly sensitive troponin

  3 months

Study Arms (2)

Ticagrelor

ACTIVE COMPARATOR

Ticagrelor 60mg BD for 3 months

Drug: Ticagrelor 60 mg

Aspirin

ACTIVE COMPARATOR

Aspirin 100mg daily for 3 months

Drug: Aspirin 100 MG Oral Tablet, Enteric Coated

Interventions

Ticagrelor 60 mg DRUG

Potent antiplatelet agent, 60mg twice daily for 3 months

Also known as: Brilinta

Ticagrelor

Aspirin 100 MG Oral Tablet, Enteric Coated DRUG

antiplatelet agent, 100mg once daily for 3 months

Also known as: Cartia

Aspirin

Eligibility Criteria

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

You may qualify if:

• Men and women aged 18 years or above.
• Documented history of presumed spontaneous ACS (excluding known peri-procedural or definite secondary MI \[eg, due to profound hypotension, hypertensive emergency, tachycardia, or profound anemia\]) with their most recent MI occurring 18 months or more prior to randomization
• Patient currently prescribed and tolerating ASA
• Females of child-bearing potential (ie, who are not chemically or surgically sterilized or who are not post-menopause) must have a negative urine pregnancy test at enrollment (to be confirmed by blood pregnancy test at the central lab.) Females of child-bearing potential must be willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator.
• Written informed consent prior to any study specific procedures.

You may not qualify if:

• Recurrent cardiovascular event (ACS, stroke and unplanned revascularization) after the index ACS
• Planned use of ADP receptor blockers (eg, clopidogrel, ticlopidine, prasugrel), dipyridamole, or cilostazol
• Planned coronary, cerebrovascular, or peripheral arterial revascularization
• Concomitant oral or intravenous therapy with strong cytochrome P450 3A (CYP3A) inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers which cannot be stopped for the course of the study - Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir, over 1 litre daily of grapefruit juice - Substrates with narrow therapeutic index: cyclosporine, quinidine, simvastatin at doses \>40 mg daily or lovastatin at doses \>40 mg daily
• Concomitant use of vasoactive drugs or vasoactive drugs cannot be stopped.
• Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin (at venous thrombosis treatment not prophylaxis doses)
• Patients with known bleeding diathesis or coagulation disorder
• Patients with:
• Concomitant active pathological bleeding,
• A history of intracranial bleed at any time,
• A central nervous system tumour or intracranial vascular abnormality (eg, aneurysm, arteriovenous malformation) at any time,
• Intracranial or spinal cord surgery within 5 years, or
• A gastrointestinal (GI) bleed within the past 6 months, or major surgery within 30 days
• History of ischemic stroke at any time
• Patients considered to be at risk of bradycardic events (\[eg, known sick sinus syndrome or second or third degree atrioventricular (AV) block\]) unless already treated with a permanent pacemaker

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Prof. HF Tse

Hong Kong, China

Location

Related Publications (12)

• Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, Collins R, Liu LS; COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005 Nov 5;366(9497):1607-21. doi: 10.1016/S0140-6736(05)67660-X.

  PMID: 16271642 RESULT

• 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. doi: 10.1056/NEJMoa010746.

  PMID: 11519503 RESULT

• 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, Thorsen 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.

  PMID: 19717846 RESULT

• Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015 May 7;372(19):1791-800. doi: 10.1056/NEJMoa1500857. Epub 2015 Mar 14.

  PMID: 25773268 RESULT

• Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ; ACC/AHA Task Force Members; Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Dec 23;130(25):2354-94. doi: 10.1161/CIR.0000000000000133. Epub 2014 Sep 23. No abstract available.

  PMID: 25249586 RESULT

• Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, Caso P, Dudek D, Gielen S, Huber K, Ohman M, Petrie MC, Sonntag F, Uva MS, Storey RF, Wijns W, Zahger D; ESC Committee for Practice Guidelines. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011 Dec;32(23):2999-3054. doi: 10.1093/eurheartj/ehr236. Epub 2011 Aug 26. No abstract available.

  PMID: 21873419 RESULT

• Cattaneo M, Schulz R, Nylander S. Adenosine-mediated effects of ticagrelor: evidence and potential clinical relevance. J Am Coll Cardiol. 2014 Jun 17;63(23):2503-2509. doi: 10.1016/j.jacc.2014.03.031. Epub 2014 Apr 23.

  PMID: 24768873 RESULT

• Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging. 2010 Aug;26(6):631-40. doi: 10.1007/s10554-010-9616-1. Epub 2010 Mar 26.

  PMID: 20339920 RESULT

• Ras RT, Streppel MT, Draijer R, Zock PL. Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. Int J Cardiol. 2013 Sep 20;168(1):344-51. doi: 10.1016/j.ijcard.2012.09.047. Epub 2012 Oct 4.

  PMID: 23041097 RESULT

• Bonello L, Laine M, Kipson N, Mancini J, Helal O, Fromonot J, Gariboldi V, Condo J, Thuny F, Frere C, Camoin-Jau L, Paganelli F, Dignat-George F, Guieu R. Ticagrelor increases adenosine plasma concentration in patients with an acute coronary syndrome. J Am Coll Cardiol. 2014 Mar 11;63(9):872-7. doi: 10.1016/j.jacc.2013.09.067. Epub 2013 Nov 27.

  PMID: 24291273 RESULT

• Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, Mas JL, Goto S, Liau CS, Richard AJ, Rother J, Wilson PW; REACH Registry Investigators. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA. 2006 Jan 11;295(2):180-9. doi: 10.1001/jama.295.2.180.

  PMID: 16403930 RESULT

• Tam CF, Chan YH, Wong YK, Li Z, Zhu X, Su KJ, Ganguly A, Hwa K, Ling XB, Tse HF. Multi-Omics Signatures Link to Ticagrelor Effects on Vascular Function in Patients With Acute Coronary Syndrome. Arterioscler Thromb Vasc Biol. 2022 Jun;42(6):789-798. doi: 10.1161/ATVBAHA.121.317513. Epub 2022 Apr 7.

  PMID: 35387483 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Ticagrelor; Aspirin; Tablets; Diltiazem

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular 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; Dosage Forms; Pharmaceutical Preparations; Benzazepines

Study Design

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

Model Details: Ticagrelor or Aspirin

Study Record Dates

• First Submitted: March 5, 2019
• First Posted: March 20, 2019
• Study Start: January 1, 2017
• Primary Completion: December 21, 2018
• Study Completion: December 21, 2018
• Last Updated: March 20, 2019

Record last verified: 2019-03

Locations

CN (1)