PercutaNEOus Coronary Intervention Followed by Monotherapy INstead of Dual Antiplatelet Therapy in the SETting of Acute Coronary Syndromes: The NEO-MINDSET Trial

Acute Coronary Syndrome Clinical Trial

— NEOMINDSET  

Official title:

PercutaNEOus Coronary Intervention Followed by Monotherapy INstead of Dual Antiplatelet Therapy in the SETting of Acute Coronary Syndromes: The NEO-MINDSET Trial A Drug Reduction Study for Patients With Acute Coronary Syndrome in the Unified Health System in Brazil

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04360720
• Other study ID #: 3992
• Status: Recruiting
• Phase: Phase 3
• Start date: October 15, 2020
• Est. completion date: January 30, 2024

Study information

• Verified date: February 2023
• Source: Hospital Israelita Albert Einstein
• Contact: Pedro A Lemos, MD
• Phone: +55 (11) 98317-5000
• Email: pedro.lemos[@]einstein.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase-3, randomized, multicenter, parallel-group study with blind evaluation of endpoints and intention-to-treat analysis.

The general purpose of the study is evaluate the non-inferiority hypothesis for ischemic events and the superiority hypothesis for bleeding events resulting from platelet P2Y12 receptor inhibitors given as monotherapy in comparison with conventional dual antiplatelet therapy in acute coronary syndrome patients treated with percutaneous coronary intervention in the context of the Unified Health System in Brazil.

Description:

Based on current scientific evidence, acute coronary syndrome subjects should be treated with dual antiplatelet therapy, which consists of the association of acetylsalicylic acid with an oral antagonist of platelet P2Y12 receptor. Clinical trials have shown that dual antiplatelet therapy reduces ischemic events, despite of increasing the risk of bleeding complications. Because dual antiplatelet therapy has a positive net effect, such an approach is currently recommended by international guidelines and recognized as the therapy of choice for acute coronary syndrome subjects. It is known that the acetylsalicylic acid dose is directly proportional to the bleeding risk. However, so far, all new antiplatelet drugs have been tested and used in association with acetylsalicylic acid for a varying period of time. This study is carried out in such context and intends to evaluate the clinical performance of new inhibitors of platelet P2Y12 receptor given solely, as monotherapy, to acute coronary syndrome patients, to test the hypothesis that an antithrombotic monotherapy with such agents (i.e., acetylsalicylic acid withdrawal) sustains efficacy by preventing ischemic complications while reducing the bleeding potential of this drug dosage regimens. It is a Phase-3, randomized, multicenter, parallel-group study with blind evaluation of endpoints and intention-to-treat analysis. Subjects with acute coronary syndrome treated with a successful percutaneous coronary intervention will be enrolled. The general purpose of the study is to test the non-inferiority hypothesis for ischemic events and the superiority hypothesis for bleeding events resulting from platelet P2Y12 receptor inhibitors given as monotherapy in comparison with conventional dual antiplatelet therapy in the context of the Unified Health System in Brazil.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3400
• Est. completion date: January 30, 2024
• Est. primary completion date: January 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subjects must meet all the criteria below:

1. Age >=18 years;

2. Clinical presentation compatible with acute coronary syndrome with onset < 24 hours before admission;

3. Successful percutaneous coronary intervention(s) of all target lesions (culprit and non-culprit) with new-generation drug-eluting stents;

4. Length of stay in hospital at randomization < 96 hours;

5. Subjects will be informed about the nature of the study and must agree to comply and give an informed consent in writing using a form approved in advance by the local Ethics Committee.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded:

1. Acute coronary syndrome on index admission treated in a conservative way or by unsuccessful percutaneous intervention or surgically;

2. Presence of residual lesions which are likely to require future treatment in the next 12 months;

3. Fibrinolytic therapy < 24 hour before randomization;

4. Need of oral anticoagulation with warfarin or new anticoagulants;

5. Chronic bleeding diathesis;

6. Active or recent major bleeding (in-hospital);

7. Prior intracranial hemorrhage;

8. Ischemic cerebrovascular accident < 30 days;

9. Presence of brain arteriovenous malformation;

10. Index event of non-atherothrombotic etiology (i.e., stent thrombosis, coronary embolism, spontaneous coronary artery dissection, myocardial ischemia due to supply/demand imbalance);

11. Potential or scheduled cardiac or non-cardiac surgery in the next 12 months;

12. Platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3;

13. Total white blood count < 3,000 cells/mm3;

14. Suspected or documented active liver disease (including laboratory evidence of hepatitis B or C);

15. Receiver of heart transplant;

16. Known allergies or intolerance of acetylsalicylic acid, clopidogrel, ticlopidine, ticagrelor, prasugrel, heparin or antiproliferative agents from the limus-family of drugs;

17. Subject with life expectation lower than 1 year;

18. Any significant medical condition that, in the investigator's opinion, could interfere with the ideal participation of the subject in the study;

19. Participation in other study in the past 12 months, unless a direct benefit to the subject can be expected.

20. Impossibility of being treated with dual antiplatelet therapy for 12 months, based on investigator judgement.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Syndrome

Intervention

Drug:
• Antiplatelet Monotherapy
All subjects randomized to Monotherapy Group will have acetylsalicylic acid discontinued immediately after randomization. Subjects randomized to Monotherapy Group will be treated with ticagrelor or prasugrel alone until the end of the study, at Month 12.

Locations

Country	Name	City	State
Brazil	Centro de Pesquisa Clínica do Coração	Aracaju	SE
Brazil	Hospital Felício Rocho	Belo Horizonte	MG
Brazil	Hospital Madre Teresa	Belo Horizonte	MG
Brazil	Hospital Universitário Ciências Médicas de Belo Horizonte	Belo Horizonte	MG
Brazil	Instituto Orizonti	Belo Horizonte	Minas Gerais
Brazil	UPECLIN	Botucatu	São Paulo
Brazil	Hospital Universitário São Francisco na Providência de Deus	Bragança Paulista	SP
Brazil	Hospital de Base de Brasília	Brasília	DF
Brazil	Instituto Aramari APO	Brasília	DF
Brazil	Instituição, Hospital e Maternidade Celso Pierro	Campinas	SP
Brazil	Instituto De Pesquisa Clinica de Campinas	Campinas	São Paulo
Brazil	CASSEMS	Campo Grande	Mato Grosso Do Sul
Brazil	Hospital Universitário Maria Aparecida Pedrossian	Campo Grande	MS
Brazil	Pontifícia Universidade Católica do Paraná	Curitiba	Paraná
Brazil	Hospital Baia Sul	Florianópolis	SC
Brazil	Hospital Instituto de Cardiologia de SC	Florianópolis	SC
Brazil	Hospital de Messejana Dr. Carlos Alberto Studart Gomes	Fortaleza	CE
Brazil	Universidade Federal de Goiás	Goiânia	GO
Brazil	Eurolatino	Juiz De Fora	Minas Gerais
Brazil	Instituto Cardiovascular de Linhares	Linhares	ES
Brazil	Irmandade da Santa Casa de Misericórdia de Marilia	Marilia	SP
Brazil	Instituto Atena de Pesquisa	Natal	Rio Grande Do Norte
Brazil	Santa Casa da Misericórdia de Passos	Passos	Minas Gerais
Brazil	Hospital Santa Lucia	Poços De Caldas	MG
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	RS
Brazil	Hospital São Lucas da PUCRS	Porto Alegre	RS
Brazil	Instituto de Cardiologia do RS - Fundação Universitária de Cardiologi	Porto Alegre	RS
Brazil	Hospital Regional de Presidente Prudente	Presidente Prudente	São Paulo
Brazil	Hospital Real Português	Recife	PE
Brazil	Instituto de Medicina Integral Professor Fernando Figueira - IMIP	Recife	Pernambuco
Brazil	Acurácia Serviços Médicos	Rio Branco	Acre
Brazil	Hospital São Lucas	Rio De Janeiro	RJ
Brazil	HUPE - Hospital Universitário Pedro Ernesto	Rio De Janeiro	RJ
Brazil	Instituto Estadual de Cardiologia Aloysio de Castro	Rio De Janeiro
Brazil	Instituto Nacional de Cardiologia - INC	Rio De Janeiro	RJ
Brazil	Hospital Ana Nery	Salvador	BA
Brazil	Santa Casa da Misericórdia de Santos	Santos	SP
Brazil	Hospital de Base	São José Do Rio Preto	São Paulo
Brazil	Hospital 9 de Julho	São Paulo	SP
Brazil	Hospital Dante Pazzanese	São Paulo	SP
Brazil	Hospital Israelita Albert Einstein	São Paulo
Brazil	Hospital São Paulo - Unifesp	São Paulo
Brazil	Instituto de Assistência Médica ao Servidor Público Estadual	São Paulo	SP
Brazil	Instituto do Coração - InCor	São Paulo	SP
Brazil	Real e Benemérita Associação Portuguesa de Beneficência	São Paulo	SP
Brazil	Santa Casa de São Paulo	São Paulo	SP
Brazil	Hospital de Clínicas da Universidade Federal do Triângulo Mineiro	Uberaba	MG
Brazil	Hospital Evangélico de Vila Velha	Vila Velha	ES
Brazil	Hospital Santa Casa de Misericórdia de Vitória	Vitória	ES

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein

Country where clinical trial is conducted

Brazil, 

References & Publications (19)

Colombo A, Hall P, Nakamura S, Almagor Y, Maiello L, Martini G, Gaglione A, Goldberg SL, Tobis JM. Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation. 1995 Mar 15;91(6):1676-88. doi: 10.1161/01.cir.91.6.1676. — View Citation

Feres F, Costa RA, Siqueira D, Costa JR Jr, Chamie D, Staico R, Chaves AJ, Abizaid A, Marin-Neto JA, Rassi A Jr, Botelho R, Alves CMR, Saad JA, Mangione JA, Lemos PA, Quadros AS, Queiroga MAC, Cantarelli MJC, Figueira HR. DIRETRIZ DA SOCIEDADE BRASILEIRA DE CARDIOLOGIA E DA SOCIEDADE BRASILEIRA DE HEMODINAMICA E CARDIOLOGIA INTERVENCIONISTA SOBRE INTERVENCAO CORONARIA PERCUTANEA. Arq Bras Cardiol. 2017 Jun;109(1 Suppl 1):1-81. doi: 10.5935/abc.20170111. No abstract available. Portuguese. — View Citation

Frigoli E, Smits P, Vranckx P, Ozaki Y, Tijssen J, Juni P, Morice MC, Onuma Y, Windecker S, Frenk A, Spaulding C, Chevalier B, Barbato E, Tonino P, Hildick-Smith D, Roffi M, Kornowski R, Schultz C, Lesiak M, Iniguez A, Colombo A, Alasnag M, Mullasari A, James S, Stankovic G, Ong PJL, Rodriguez AE, Mahfoud F, Bartunek J, Moschovitis A, Laanmets P, Leonardi S, Heg D, Sunnaker M, Valgimigli M. Design and rationale of the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen (MASTER DAPT) Study. Am Heart J. 2019 Mar;209:97-105. doi: 10.1016/j.ahj.2018.10.009. Epub 2018 Nov 22. — View Citation

Garcia-Garcia HM, McFadden EP, Farb A, Mehran R, Stone GW, Spertus J, Onuma Y, Morel MA, van Es GA, Zuckerman B, Fearon WF, Taggart D, Kappetein AP, Krucoff MW, Vranckx P, Windecker S, Cutlip D, Serruys PW; Academic Research Consortium. Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document. Circulation. 2018 Jun 12;137(24):2635-2650. doi: 10.1161/CIRCULATIONAHA.117.029289. — View Citation

Kogame N, Modolo R, Tomaniak M, Cavalcante R, de Martino F, Tinoco J, Ribeiro EE, Mehran R, Campos CM, Onuma Y, Lemos PA, Serruys PW; Collaborators. Prasugrel monotherapy after PCI with the SYNERGY stent in patients with chronic stable angina or stabilised acute coronary syndromes: rationale and design of the ASET pilot study. EuroIntervention. 2019 Aug 9;15(6):e547-e550. doi: 10.4244/EIJ-D-19-00131. No abstract available. — View Citation

Lansky AJ, Messe SR, Brickman AM, Dwyer M, Bart van der Worp H, Lazar RM, Pietras CG, Abrams KJ, McFadden E, Petersen NH, Browndyke J, Prendergast B, Ng VG, Cutlip DE, Kapadia S, Krucoff MW, Linke A, Scala Moy C, Schofer J, van Es GA, Virmani R, Popma J, Parides MK, Kodali S, Bilello M, Zivadinov R, Akar J, Furie KL, Gress D, Voros S, Moses J, Greer D, Forrest JK, Holmes D, Kappetein AP, Mack M, Baumbach A. Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative. Eur Heart J. 2018 May 14;39(19):1687-1697. doi: 10.1093/eurheartj/ehx037. — 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

Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available. — View Citation

Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, Antman EM; TRITON-TIMI 38 investigators. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet. 2009 Feb 28;373(9665):723-31. doi: 10.1016/S0140-6736(09)60441-4. — View Citation

Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussieres JS, Wallace S; ATACAS Investigators of the ANZCA Clinical Trials Network. Stopping vs. Continuing Aspirin before Coronary Artery Surgery. N Engl J Med. 2016 Feb 25;374(8):728-37. doi: 10.1056/NEJMoa1507688. — View Citation

Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Baggish JS, Bhatt DL, Topol EJ. Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials. Am J Cardiol. 2005 May 15;95(10):1218-22. doi: 10.1016/j.amjcard.2005.01.049. — View Citation

Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction; Thygesen K, Alpert JS, White HD, Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA, Chaitman BA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S; ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-67. doi: 10.1093/eurheartj/ehs184. Epub 2012 Aug 24. No abstract available. — View Citation

Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, Cuisset T, Cutlip D, Eerdmans P, Eikelboom J, Farb A, Gibson CM, Gregson J, Haude M, James SK, Kim HS, Kimura T, Konishi A, Laschinger J, Leon MB, Magee PFA, Mitsutake Y, Mylotte D, Pocock S, Price MJ, Rao SV, Spitzer E, Stockbridge N, Valgimigli M, Varenne O, Windhoevel U, Yeh RW, Krucoff MW, Morice MC. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J. 2019 Aug 14;40(31):2632-2653. doi: 10.1093/eurheartj/ehz372. — View Citation

Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN; ESC Scientific Document Group; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018 Jan 14;39(3):213-260. doi: 10.1093/eurheartj/ehx419. No abstract available. — View Citation

Valgimigli M, Frigoli E, Leonardi S, Rothenbuhler M, Gagnor A, Calabro P, Garducci S, Rubartelli P, Briguori C, Ando G, Repetto A, Limbruno U, Garbo R, Sganzerla P, Russo F, Lupi A, Cortese B, Ausiello A, Ierna S, Esposito G, Presbitero P, Santarelli A, Sardella G, Varbella F, Tresoldi S, de Cesare N, Rigattieri S, Zingarelli A, Tosi P, van 't Hof A, Boccuzzi G, Omerovic E, Sabate M, Heg D, Juni P, Vranckx P; MATRIX Investigators. Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes. N Engl J Med. 2015 Sep 10;373(11):997-1009. doi: 10.1056/NEJMoa1507854. Epub 2015 Sep 1. — View Citation

Valgimigli M, Garcia-Garcia HM, Vrijens B, Vranckx P, McFadden EP, Costa F, Pieper K, Vock DM, Zhang M, Van Es GA, Tricoci P, Baber U, Steg G, Montalescot G, Angiolillo DJ, Serruys PW, Farb A, Windecker S, Kastrati A, Colombo A, Feres F, Juni P, Stone GW, Bhatt DL, Mehran R, Tijssen JGP. Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC). Eur Heart J. 2019 Jul 1;40(25):2070-2085. doi: 10.1093/eurheartj/ehy377. Erratum In: Eur Heart J. 2019 Sep 1;40(33):2774. Eur Heart J. 2019 Jul 1;40(25):2086-2088. — View Citation

Vranckx P, Valgimigli M, Juni P, Hamm C, Steg PG, Heg D, van Es GA, McFadden EP, Onuma Y, van Meijeren C, Chichareon P, Benit E, Mollmann H, Janssens L, Ferrario M, Moschovitis A, Zurakowski A, Dominici M, Van Geuns RJ, Huber K, Slagboom T, Serruys PW, Windecker S; GLOBAL LEADERS Investigators. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet. 2018 Sep 15;392(10151):940-949. doi: 10.1016/S0140-6736(18)31858-0. Epub 2018 Aug 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, 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. — View Citation

Xian Y, Wang TY, McCoy LA, Effron MB, Henry TD, Bach RG, Zettler ME, Baker BA, Fonarow GC, Peterson ED. Association of Discharge Aspirin Dose With Outcomes After Acute Myocardial Infarction: Insights From the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) Study. Circulation. 2015 Jul 21;132(3):174-81. doi: 10.1161/CIRCULATIONAHA.114.014992. Epub 2015 May 20. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite endpoint of all-cause mortality, cerebrovascular accident, myocardial infarction or urgent target vessel revascularization.	Co-Primary Efficacy Endpoint (non-inferiority hypothesis)	12 months
Primary	Bleeding Academic Research Consortium (BARC) type-2, -3 or -5 bleeding event	Co-Primary Safety Endpoint (superiority hypothesis)	12 months
Secondary	Total of deaths, and cardiac and non-cardiac deaths	Total of deaths, and cardiac and non-cardiac deaths	12 months
Secondary	Sudden death	Sudden death	30 days
Secondary	Cerebrovascular accident	Cerebrovascular accident	12 months
Secondary	Myocardial Infarction	Myocardial Infarction	12 months
Secondary	Stent thrombosis	Stent thrombosis	12 months
Secondary	Non-scheduled invasive coronary treatment	Non-scheduled invasive coronary treatment	12 months
Secondary	BARC 1-5 type bleeding	BARC 1-5 type bleeding	12 months
Secondary	Composite net adverse event (occurrence of co-primary efficacy endpoint or co-primary safety endpoint)	Composite net adverse event (occurrence of co-primary efficacy endpoint or co-primary safety endpoint)	12 months
Secondary	Cost-effectiveness ratio	Cost-effectiveness ratio	12 months