OPTImal Management of Antithrombotic Agents: OPTIMA-2 Trial

NCT01955200 | Completed Phase 4

• 1 other identifier: 001
• Study Type: interventional
• Target: 1,724
• Locations: 1 country
• Sites: 1

Brief Summary

High on-treatment platelet reactivity (HOPR) is associated with increased risk of cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We sought to investigate the efficacy and safety of 1-month intensified antiplatelet therapies in post-PCI patients with HOPR.

Conditions

Coronary Artery Disease

Keywords

Stent implantation; High on-treatment platelet reactivity; Ticagrelor; Cilostazol; Clopidogrel

Outcome Measures

Primary Outcomes (1)

• the proportion of patients with persistent HOPR at 1 month

  platelet aggregation in response to 5μM adenosine diphosphate (PLADP) measured by light transmittancy aggregometer (LTA) ; HOPR was defined as PLADP \> 40%.

  1-month after randomization

Secondary Outcomes (1)

• MACE

  1-year after randomization

Other Outcomes (1)

• Bleeding

  1-year after randomization

Study Arms (5)

CLOP-150

EXPERIMENTAL

clopidogrel 150mg once daily

Drug: Clopidogrel

CLOP+CILOST

EXPERIMENTAL

clopidogrel 75mg once daily plus cilostazol 100mg twice daily

Drug: Cilostazol

TICAG

EXPERIMENTAL

ticagrelor 90mg twice daily

Drug: Ticagrelor

CON(conventional DAPT)

ACTIVE COMPARATOR

clopidogrel 75mg once daily

Drug: Clopidogrel

Non-HOPR

ACTIVE COMPARATOR

clopidogrel 75mg once daily

Drug: Clopidogrel

Interventions

Clopidogrel DRUG

(ASA 100mg daily + Clopidogrel 150mg daily) x 1 month; (ASA 100mg daily + Clopidogrel 75mg daily) x 11 month.

Also known as: Plavix

CLOP-150

Cilostazol DRUG

(ASA 100mg daily + Clopidogrel 75mg daily + Cilostazol 150mg Bid) x 1 month; (ASA 100mg daily + Clopidogrel 75mg daily) x 11 month.

Also known as: Peida

CLOP+CILOST

Ticagrelor DRUG

(ASA 100mg daily + Ticagrelor 90mg Bid) x 1 month; (ASA 100mg daily + Clopidogrel 75mg daily) x 11 month.

Also known as: Brilinta

TICAG

Eligibility Criteria

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

You may qualify if:

• Successively recruit all patients who receive stent implantation;
• Intended use of standard DAPT with the combination of aspirin 100mg once daily and clopidogrel 75mg once daily for at least 12 months;
• Patient aged \>18 years and ≦80 years old;
• Signed inform consent.

You may not qualify if:

• Allergy or intolerance to study drugs;
• History of gastrointestinal or intracranial bleeding;
• Need for anticoagulant therapy;
• High risk of bleeding (e.g., myelodysplasia, baseline platelet count \< 80 × 109/L);
• Hemoglobin \< 90g/L;
• Active malignancy or life expectancy \< 1 year;
• Patients with other conditions made them unsuitable to be recruited at the discretion of the investigators.

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 (12)

• 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 BACKGROUND

• Main C, Palmer S, Griffin S, Jones L, Orton V, Sculpher M, Henderson R, Sudlow C, Hawkins N, Riemsma R. Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment-elevation acute coronary syndromes: a systematic review and economic evaluation. Health Technol Assess. 2004 Oct;8(40):iii-iv, xv-xvi, 1-141. doi: 10.3310/hta8400.

  PMID: 15461878 BACKGROUND

• Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006 Apr 20;354(16):1706-17. doi: 10.1056/NEJMoa060989. Epub 2006 Mar 12.

  PMID: 16531616 BACKGROUND

• Kronzon I, Feit F. Clopidogrel plus aspirin was effective but increased bleeding in acute coronary syndromes without ST-segment elevation. ACP J Club. 2002 Mar-Apr;136(2):45. No abstract available.

  PMID: 11874270 BACKGROUND

• De Miguel A, Ibanez B, Badimon JJ. Clinical implications of clopidogrel resistance. Thromb Haemost. 2008 Aug;100(2):196-203.

  PMID: 18690337 BACKGROUND

• Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB, Faxon DP, Rupprecht HJ, Budaj A, Avezum A, Widimsky P, Steg PG, Bassand JP, Montalescot G, Macaya C, Di Pasquale G, Niemela K, Ajani AE, White HD, Chrolavicius S, Gao P, Fox KA, Yusuf S; CURRENT-OASIS 7 trial investigators. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010 Oct 9;376(9748):1233-43. doi: 10.1016/S0140-6736(10)61088-4.

  PMID: 20817281 BACKGROUND

• 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 BACKGROUND

• Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D, Puri S, Robbins M, Garratt KN, Bertrand OF, Stillabower ME, Aragon JR, Kandzari DE, Stinis CT, Lee MS, Manoukian SV, Cannon CP, Schork NJ, Topol EJ; GRAVITAS Investigators. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011 Mar 16;305(11):1097-105. doi: 10.1001/jama.2011.290.

  PMID: 21406646 BACKGROUND

• Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, Orban M, Hadamitzky M, Merkely B, Kiss RG, Komocsi A, Dezsi CA, Holdt L, Felix SB, Parma R, Klopotowski M, Schwinger RHG, Rieber J, Huber K, Neumann FJ, Koltowski L, Mehilli J, Huczek Z, Massberg S; TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017 Oct 14;390(10104):1747-1757. doi: 10.1016/S0140-6736(17)32155-4. Epub 2017 Aug 28.

  PMID: 28855078 BACKGROUND

• Deharo P, Quilici J, Camoin-Jau L, Johnson TW, Bassez C, Bonnet G, Fernandez M, Ibrahim M, Suchon P, Verdier V, Fourcade L, Morange PE, Bonnet JL, Alessi MC, Cuisset T. Benefit of Switching Dual Antiplatelet Therapy After Acute Coronary Syndrome According to On-Treatment Platelet Reactivity: The TOPIC-VASP Pre-Specified Analysis of the TOPIC Randomized Study. JACC Cardiovasc Interv. 2017 Dec 26;10(24):2560-2570. doi: 10.1016/j.jcin.2017.08.044.

  PMID: 29268886 BACKGROUND

• Ying L, Wang J, Li J, Teng J, Zhang X, Ullah I, Samee A, Xu K, Chen J, Xu L, Zhu H, Li J, Yang L, Wang F, Fan Y, Zhang J, Lu Y, Gong X, Shi L, Eikelboom JW, Li C. Intensified antiplatelet therapy in patients after percutaneous coronary intervention with high on-treatment platelet reactivity: the OPTImal Management of Antithrombotic Agents (OPTIMA)-2 Trial. Br J Haematol. 2022 Jan;196(2):424-432. doi: 10.1111/bjh.17847. Epub 2021 Oct 5.

  PMID: 34611892 DERIVED

• Wang J, Abdus S, Tan C, Gu Q, Yang M, Wang G, Shi L, Gong X, Li C. Serum uric acid level negatively correlated with the prevalence of clopidogrel low response in patients undergoing antiplatelet treatment with aspirin and clopidogrel. Nutr Metab Cardiovasc Dis. 2020 Nov 27;30(12):2215-2220. doi: 10.1016/j.numecd.2020.07.025. Epub 2020 Jul 24.

  PMID: 32912788 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Clopidogrel; Cilostazol; Ticagrelor

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular 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; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 28, 2013
• First Posted: October 7, 2013
• Study Start: October 5, 2013
• Primary Completion: December 26, 2016
• Study Completion: November 28, 2017
• Last Updated: August 18, 2020

Record last verified: 2020-08

Locations

CN (1)