Coronary Artery EctasiaPhase 4OVER-TIME IINCT07511257
Multicenter Trial of Antithrombotic Strategies in Acute Coronary Syndrome With Coronary Artery Ectasia
A Phase 4 study testing Aspirin 100 mg, Clopidogrel 75 mg and Rivaroxaban 15 mg in people with Coronary Artery Ectasia and Acute Coronary Syndromes (ACS), run by Instituto Nacional de Cardiologia Ignacio Chavez at 1 site in Mexico.
Trial summary
Coronary artery ectasia (CAE) is a condition in which a coronary artery becomes abnormally dilated, measuring at least 50% larger than the adjacent normal segment. Although relatively uncommon, CAE is clinically important because it can lead to abnormal blood flow and increase the risk of blood clot formation. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Artery Ectasia, Acute Coronary Syndromes (ACS), STEMI - ST Elevation Myocardial Infarction
- What is being tested?
- Aspirin 100 mg, Clopidogrel 75 mg and Rivaroxaban 15 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 326 participants
- Where
- 1 siteMexico
- Study dates
- 11 Feb 2026to Jun 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18 to 80 years, of either sex, hospitalized with acute coronary syndrome (ACS) with or without ST-segment elevation.
- Recent ACS within 7 days prior to enrollment, defined by all of the following:
- Clinical presentation consistent with acute coronary syndrome.
- Elevated high-sensitivity cardiac troponin above the 99th percentile.
- Presence or absence of persistent ST-segment elevation.
- Coronary artery ectasia in the culprit coronary artery, defined by all of the following:
Show all 11Show fewer
- The presence of ectasia will be determined by agreement of two expert interventional cardiologists, and will be confirmed by quantitative coronary angiography (QCA).
- Identification of a culprit artery consistent with the electrocardiographic territory involved (in cases with ST-segment elevation) or with angiographic features suggestive of an atherothrombotic event, such as the presence of thrombus or reduced coronary flow.
- Hospital admission lasting more than 24 hours.
- Management with either percutaneous coronary intervention or medical therapy, as determined by the treating medical team. Intracoronary interventions such as stent implantation, balloon angioplasty, or thrombus aspiration are permitted.
- Ability and willingness to provide written informed consent and to participate in the study.
Who cannot join
- Pregnant women.
- Current indication for temporary or long-term anticoagulation therapy at the time of enrollment.
- Severe chronic kidney disease, defined as KDIGO stage G4 or higher (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m²).
- Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² at hospital discharge.
- History of major bleeding, active bleeding, or high bleeding risk, including but not limited to gastrointestinal bleeding, intracranial hemorrhage, or other conditions considered by the treating physician to confer a high risk of bleeding.
- Advanced heart failure, defined as left ventricular ejection fraction (LVEF) <30% plus at least one of the following:
- More than two hospitalizations or unplanned emergency department visits for heart failure in the past year, or
- NYHA functional class III or IV symptoms despite optimal medical therapy at enrollment or within the previous 3 months.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Direccion de Investigación Instituto Nacional de Cardiología contact
Mexico1 site, 1 recruiting
- Recruiting
Instituto Nacional de Cardiologia "Ignacio Chávez"
Mexico City, Tlalpan, 14080
Comite de Investigación, +52 5555732911, comite.investigacion@cardiologia.org.mx
Diego Araiza Garaygordobil, MD MSc PhD
About this study
Official title: Dual Antiplatelet Therapy Versus Antiplatelet Monotherapy Plus Anticoagulation in Patients With Acute Coronary Syndrome and Coronary Artery Ectasia: A Multicenter Randomized Clinical Trial
Coronary artery ectasia (CAE) is a condition in which a coronary artery becomes abnormally dilated, measuring at least 50% larger than the adjacent normal segment. Although relatively uncommon, CAE is clinically important because it can lead to abnormal blood flow and increase the risk of blood clot formation. Patients with CAE are at higher risk of angina, myocardial infarction, and complications during coronary interventions. Despite these risks, the optimal antithrombotic treatment for patients with acute coronary syndrome (ACS) and CAE remains uncertain.
Dual antiplatelet therapy (aspirin plus clopidogrel) is currently the most commonly used treatment. However, the abnormal blood flow patterns observed in CAE may promote clot formation through mechanisms that could potentially be better addressed with anticoagulant therapy.
The OVER-TIME II trial is a multicenter randomized clinical trial designed to compare two antithrombotic strategies in patients with ACS and CAE: standard dual antiplatelet therapy versus antiplatelet monotherapy combined with anticoagulation. The study aims to determine whether the addition of anticoagulation reduces major cardiovascular events without significantly increasing bleeding risk.
Read the detailed description
Coronary artery ectasia (CAE) is defined as an abnormal dilatation of a coronary artery segment measuring at least 50% greater than the diameter of the adjacent normal segment. Although relatively uncommon, CAE represents a clinically relevant phenotype of coronary artery disease. Its reported prevalence ranges from 0.3% to 4.9% worldwide; however, higher frequencies have been described in certain populations. At the National Institute of Cardiology "Ignacio Chávez" (INCICh) in Mexico, a prevalence of approximately 10.3% has been documented among patients presenting with ST-segment elevation myocardial infarction (STEMI), highlighting the importance of studying this condition in the Mexican population.
The pathophysiology of CAE involves abnormal coronary blood flow dynamics, including turbulent flow and blood stasis within dilated segments. These changes may promote thrombus formation through multiple mechanisms, including platelet activation, local inflammatory processes, endothelial dysfunction, and potential prothrombotic states. Genetic susceptibility and molecular pathways related to vascular remodeling may also contribute to the development and progression of the disease. Clinically, patients with CAE have been associated with a higher risk of angina, myocardial infarction, distal embolization, and complications during percutaneous coronary intervention.
Despite its clinical significance, the optimal antithrombotic strategy in patients with acute coronary syndrome (ACS) and CAE remains uncertain. Dual antiplatelet therapy (DAPT), typically consisting of aspirin and a P2Y12 inhibitor, is the most commonly used treatment. However, given the propensity for thrombus formation related to abnormal flow conditions in ectatic coronary segments, anticoagulation has been proposed as a potentially beneficial therapeutic strategy.
The exploratory OVERTIME trial conducted at INCICh compared an antithrombotic regimen consisting of antiplatelet monotherapy plus a direct oral anticoagulant (clopidogrel 75 mg plus rivaroxaban 15 mg daily) with standard dual antiplatelet therapy (aspirin 100 mg plus clopidogrel 75 mg daily) in patients with ACS and CAE. Although limited by sample size, the study demonstrated a numerical reduction in major adverse cardiovascular events and a shorter endogenous fibrinolysis time among patients receiving the combination of antiplatelet therapy and anticoagulation, without a significant increase in bleeding events.
These findings support the hypothesis that anticoagulation combined with antiplatelet therapy may improve clinical outcomes in this high-risk population. However, larger randomized studies are needed to confirm these results and provide definitive evidence to guide clinical management.
The OVER-TIME II trial is a multicenter, randomized clinical trial designed to compare two antithrombotic strategies in patients with ACS and angiographically confirmed CAE: (1) standard dual antiplatelet therapy and (2) antiplatelet monotherapy combined with oral anticoagulation. The primary objective is to evaluate whether the addition of anticoagulation reduces major cardiovascular events without significantly increasing bleeding risk.
In addition to the clinical trial component, the study will incorporate a translational research arm. Peripheral blood samples will be collected to investigate genetic variants and DNA and RNA expression profiles that may be associated with susceptibility to CAE, disease progression, and differential response to antithrombotic therapy. These analyses aim to improve the understanding of the biological mechanisms underlying CAE and to identify potential biomarkers that could inform future personalized treatment strategies.
- Conditions
- Coronary Artery Ectasia, Acute Coronary Syndromes (ACS), STEMI - ST Elevation Myocardial Infarction, NSTEMI - Non-ST Segment Elevation Myocardial Infarction (MI)
- Being tested
- Aspirin 100 mg, Clopidogrel 75 mg, Rivaroxaban 15 mg
- Keywords
- Coronary Artery Ectasia, Acute Coronary Syndrome, Anticoagulation, Dual Antiplatelet Therapy
- Medical subject headings
- Coronary Aneurysm, Acute Coronary Syndrome, ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspirin 100 mgDrug
Participants receive aspirin 100 mg once daily
Clopidogrel 75 mgDrug
Participants receive clopidogrel 75 mg once daily
Rivaroxaban 15 mgDrug
Participants receive oral anticoagulation using rivaroxaban 15 mg once daily
| Study group | Role | What they receive |
|---|---|---|
| Dual Antiplatelet Therapy | Active comparator | Participants receive standard dual antiplatelet therapy consisting of aspirin 100 mg once daily plus clopidogrel 75 mg once daily Receives: Drug: Aspirin 100 mg; Drug: Clopidogrel 75 mg |
| Antiplatelet Monotherapy Plus Oral Anticoagulation | Experimental | Participants receive antiplatelet monotherapy with clopidogrel 75 mg once daily plus oral anticoagulation using rivaroxaban 15 mg once daily Receives: Drug: Clopidogrel 75 mg; Drug: Rivaroxaban 15 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to First Major Adverse Cardiovascular Event (MACE)
Time to first occurrence of the composite of cardiovascular death, non-fatal myocardial infarction, or repeat coronary revascularization in patients with coronary artery ectasia following acute coronary syndrome, according to the assigned antithrombotic treatment strategy (dual antiplatelet therapy versus clopidogrel plus rivaroxaban).
Measured: 12 months
Time to First Bleeding Event According to the BARC Classification
Time to first occurrence of a composite of major or minor bleeding events defined according to the Bleeding Academic Research Consortium (BARC) classification in patients with coronary artery ectasia following acute coronary syndrome, according to the assigned antithrombotic treatment strategy (dual antiplatelet therapy versus clopidogrel plus rivaroxaban).
Measured: 12 months
Secondary outcomes (2)
Individual Components of the Major Adverse Cardiovascular Event Composite
Incidence of each individual component of the primary efficacy composite endpoint (cardiovascular death, non-fatal myocardial infarction, and repeat coronary revascularization) in patients with coronary artery ectasia following acute coronary syndrome, according to the assigned antithrombotic treatment strategy.
Measured: 12 months
Individual Bleeding Events According to the BARC Classification
Incidence of individual bleeding events according to the Bleeding Academic Research Consortium (BARC) classification in patients with coronary artery ectasia following acute coronary syndrome, according to the assigned antithrombotic treatment strategy.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2026
- Study start11 Feb 2026
- Primary completionJun 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery EctasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 326 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Cardiologia Ignacio Chavez
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Diego Araiza-Garaygordobil, Instituto Nacional de Cardiologia Ignacio Chavez
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07511257
- Sponsor's protocol ID
- 26-1556
- Acronym
- OVER-TIME II
- Status last verified
- Apr 2026
- First submitted
- 30 Mar 2026
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Some information might be available upon reasonable request.
Publications
Solis-Jimenez F, Esparza XL, Guzman-Solorzano HP, Villalobos-Pedroza M, Morales-Villamil LA, Diaz-Herrera BA, Hernandez-Pastrana S, Gopar-Nieto R, Arias-Sanchez EA, Marroquin-Donday LA, Jimenez-Rodriguez GM, Sierra-Lara D, Araiza-Garaygordobil D, Arias-Mendoza A. Anticoagulant versus Antiplatelet Therapy After Acute Coronary Syndromes in Patients with Coronary Artery Ectasia: A Retrospective Cohort Study. Cardiovasc Drugs Ther. 2026 Jun;40(3):1021-1033. doi: 10.1007/s10557-025-07784-0. Epub 2025 Sep 24.
PubMed 40991139Araiza-Garaygordobil D, Gopar-Nieto R, Sierra-Lara Martinez JD, Mullasari AS, Belderrain-Morales N, Najera-Rojas NA, Diaz-Herrera BA, Sarabia-Chao V, Alfaro-Ponce DL, Briseno-De la Cruz JL, Ruiz-Beltran M, Martinez-Rios MA, Pina-Reyna Y, Latapi-Ruiz Esparza X, Grimaldo-Gomez FA, Cortina-De la Rosa E, Romero-Arroyo MO, Sierra-Gonzalez de Cossio A, Gonzalez-Pacheco H, Arias-Mendoza A. A randomized trial of antithrombotic therapy in patients with acute coronary syndrome and coronary ectasia. Am Heart J. 2025 Mar;281:103-111. doi: 10.1016/j.ahj.2024.11.012. Epub 2024 Nov 29.
PubMed 39615618Doi T, Kataoka Y, Noguchi T, Shibata T, Nakashima T, Kawakami S, Nakao K, Fujino M, Nagai T, Kanaya T, Tahara Y, Asaumi Y, Tsuda E, Nakai M, Nishimura K, Anzai T, Kusano K, Shimokawa H, Goto Y, Yasuda S. Coronary Artery Ectasia Predicts Future Cardiac Events in Patients With Acute Myocardial Infarction. Arterioscler Thromb Vasc Biol. 2017 Dec;37(12):2350-2355. doi: 10.1161/ATVBAHA.117.309683. Epub 2017 Oct 19.
PubMed 29051141Iwanczyk S, Lehmann T, Cieslewicz A, Malesza K, Wozniak P, Hertel A, Krupka G, Jagodzinski PP, Grygier M, Lesiak M, Araszkiewicz A. Circulating miRNA-451a and miRNA-328-3p as Potential Markers of Coronary Artery Aneurysmal Disease. Int J Mol Sci. 2023 Mar 18;24(6):5817. doi: 10.3390/ijms24065817.
PubMed 36982889Lu TP, Chuang NC, Cheng CY, Hsu CA, Wang YC, Lin YH, Lee JK, Wu CK, Hwang JJ, Lin LY, Yeh SS, Chien KL, Juang JJ. Genome-wide methylation profiles in coronary artery ectasia. Clin Sci (Lond). 2017 Apr 1;131(7):583-594. doi: 10.1042/CS20160821. Epub 2017 Jan 31.
PubMed 28143891Dogan A, Tunc B, Ergene O, Ozaydin M, Nazli C, Altinbas A, Gedikli O. Evaluation of overall fibrinolytic activity in patients with coronary artery ectasia: global fibrinolytic capacity. Int J Cardiovasc Imaging. 2003 Dec;19(6):465-71. doi: 10.1023/b:caim.0000004339.30038.8d.
PubMed 14690185Nunez-Gil IJ, Cerrato E, Bollati M, Nombela-Franco L, Terol B, Alfonso-Rodriguez E, Camacho Freire SJ, Villablanca PA, Amat Santos IJ, de la Torre Hernandez JM, Pascual I, Liebetrau C, Camacho B, Pavani M, Albistur J, Latini RA, Varbella F, Jimenez-Diaz VA, Piraino D, Mancone M, Alfonso F, Linares JA, Rodriguez-Olivares R, Jimenez Mazuecos JM, Palazuelos Molinero J, Sanchez-Grande Flecha A, Gomez-Hospital JA, Ielasi A, Lozano I, Omede P, Bagur R, Ugo F, Medda M, Louka BF, Kala P, Escaned J, Bautista D, Feltes G, Salinas P, Alkhouli M, Macaya C, Fernandez-Ortiz A; CAAR investigators. Coronary artery aneurysms, insights from the international coronary artery aneurysm registry (CAAR). Int J Cardiol. 2020 Jan 15;299:49-55. doi: 10.1016/j.ijcard.2019.05.067. Epub 2019 Jul 19.
PubMed 31378382Gunasekaran P, Stanojevic D, Drees T, Fritzlen J, Haghnegahdar M, McCullough M, Barua R, Mehta A, Hockstad E, Wiley M, Earnest M, Tadros P, Genton R, Gupta K. Prognostic significance, angiographic characteristics and impact of antithrombotic and anticoagulant therapy on outcomes in high versus low grade coronary artery ectasia: A long-term follow-up study. Catheter Cardiovasc Interv. 2019 Jun 1;93(7):1219-1227. doi: 10.1002/ccd.27929. Epub 2018 Nov 4.
PubMed 30393992Bogana Shanmugam V, Psaltis PJ, T L Wong D, T Meredith I, Malaiapan Y, Ahmar W. Outcomes After Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction Caused by Ectatic Infarct Related Arteries. Heart Lung Circ. 2017 Oct;26(10):1059-1068. doi: 10.1016/j.hlc.2016.12.006. Epub 2017 Feb 7.
PubMed 28216061Yip HK, Chen MC, Wu CJ, Hang CL, Hsieh KY, Fang CY, Yeh KH, Fu M. Clinical features and outcome of coronary artery aneurysm in patients with acute myocardial infarction undergoing a primary percutaneous coronary intervention. Cardiology. 2002;98(3):132-40. doi: 10.1159/000066322.
PubMed 12417812Hartnell GG, Parnell BM, Pridie RB. Coronary artery ectasia. Its prevalence and clinical significance in 4993 patients. Br Heart J. 1985 Oct;54(4):392-5. doi: 10.1136/hrt.54.4.392.
PubMed 4052280Markis JE, Joffe CD, Cohn PF, Feen DJ, Herman MV, Gorlin R. Clinical significance of coronary arterial ectasia. Am J Cardiol. 1976 Feb;37(2):217-22. doi: 10.1016/0002-9149(76)90315-5.
PubMed 1108631Swaye PS, Fisher LD, Litwin P, Vignola PA, Judkins MP, Kemp HG, Mudd JG, Gosselin AJ. Aneurysmal coronary artery disease. Circulation. 1983 Jan;67(1):134-8. doi: 10.1161/01.cir.67.1.134.
PubMed 6847792Adame-Aviles E, Araiza-Garaygordobil D, Garcia-Mena L, Alcocer-Gamba M, Maldonado-May AC, Alvarez-Santana R, Nieto-Saucedo JR, Rojas-Arriaga AI, Gopar-Nieto R, Sierra-Lara Martinez JD, Marroquin-Donday LA, Diaz-Marin J, Jacobo-Albavera L, Arias-Mendoza MA, Mullasari AS. OVER-TIME II trial: design and rationale of a multicentre randomized study evaluating antithrombotic strategies in patients with acute coronary syndrome and coronary artery ectasia. Eur Heart J Open. 2026 Sep 30;6(6):oeag161. doi: 10.1093/ehjopen/oeag161. eCollection 2026 Nov.
PubMed 42979093
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dual Antiplatelet Therapy Versus Antiplatelet Monotherapy Plus Anticoagulation in Patients With Acute Coronary Syndrome and Coronary Artery Ectasia: A Multicenter Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07511257
- Acronym / sponsor ID
- OVER-TIME II / 26-1556
- Conditions
- Coronary Artery Ectasia, Acute Coronary Syndromes (ACS), STEMI - ST Elevation Myocardial Infarction, NSTEMI - Non-ST Segment Elevation Myocardial Infarction (MI)
- Keywords
- Coronary Artery Ectasia, Acute Coronary Syndrome, Anticoagulation, Dual Antiplatelet Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 326 participants (estimated)
- Lead sponsor
- Instituto Nacional de Cardiologia Ignacio ChavezUniversity, hospital or other
- Study start
- 11 Feb 2026 (actual)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 6 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Coronary artery ectasia (CAE) is a condition in which a coronary artery becomes abnormally dilated, measuring at least 50% larger than the adjacent normal segment. Although relatively uncommon, CAE is clinically important because it can lead to abnormal blood flow and increase the risk of blood clot formation. Patients with CAE are at higher risk of angina, myocardial infarction, and complications during coronary interventions. Despite these risks, the optimal antithrombotic treatment for patients with acute coronary syndrome (ACS) and CAE remains uncertain.
Dual antiplatelet therapy (aspirin plus clopidogrel) is currently the most commonly used treatment. However, the abnormal blood flow patterns observed in CAE may promote clot formation through mechanisms that could potentially be better addressed with anticoagulant therapy.
The OVER-TIME II trial is a multicenter randomized clinical trial designed to compare two antithrombotic strategies in patients with ACS and CAE: standard dual antiplatelet therapy versus antiplatelet monotherapy combined with anticoagulation. The study aims to determine whether the addition of anticoagulation reduces major cardiovascular events without significantly increasing bleeding risk.
Detailed description
Coronary artery ectasia (CAE) is defined as an abnormal dilatation of a coronary artery segment measuring at least 50% greater than the diameter of the adjacent normal segment. Although relatively uncommon, CAE represents a clinically relevant phenotype of coronary artery disease. Its reported prevalence ranges from 0.3% to 4.9% worldwide; however, higher frequencies have been described in certain populations. At the National Institute of Cardiology "Ignacio Chávez" (INCICh) in Mexico, a prevalence of approximately 10.3% has been documented among patients presenting with ST-segment elevation myocardial infarction (STEMI), highlighting the importance of studying this condition in the Mexican population.
The pathophysiology of CAE involves abnormal coronary blood flow dynamics, including turbulent flow and blood stasis within dilated segments. These changes may promote thrombus formation through multiple mechanisms, including platelet activation, local inflammatory processes, endothelial dysfunction, and potential prothrombotic states. Genetic susceptibility and molecular pathways related to vascular remodeling may also contribute to the development and progression of the disease. Clinically, patients with CAE have been associated with a higher risk of angina, myocardial infarction, distal embolization, and complications during percutaneous coronary intervention.
Despite its clinical significance, the optimal antithrombotic strategy in patients with acute coronary syndrome (ACS) and CAE remains uncertain. Dual antiplatelet therapy (DAPT), typically consisting of aspirin and a P2Y12 inhibitor, is the most commonly used treatment. However, given the propensity for thrombus formation related to abnormal flow conditions in ectatic coronary segments, anticoagulation has been proposed as a potentially beneficial therapeutic strategy.
The exploratory OVERTIME trial conducted at INCICh compared an antithrombotic regimen consisting of antiplatelet monotherapy plus a direct oral anticoagulant (clopidogrel 75 mg plus rivaroxaban 15 mg daily) with standard dual antiplatelet therapy (aspirin 100 mg plus clopidogrel 75 mg daily) in patients with ACS and CAE. Although limited by sample size, the study demonstrated a numerical reduction in major adverse cardiovascular events and a shorter endogenous fibrinolysis time among patients receiving the combination of antiplatelet therapy and anticoagulation, without a significant increase in bleeding events.
These findings support the hypothesis that anticoagulation combined with antiplatelet therapy may improve clinical outcomes in this high-risk population. However, larger randomized studies are needed to confirm these results and provide definitive evidence to guide clinical management.
The OVER-TIME II trial is a multicenter, randomized clinical trial designed to compare two antithrombotic strategies in patients with ACS and angiographically confirmed CAE: (1) standard dual antiplatelet therapy and (2) antiplatelet monotherapy combined with oral anticoagulation. The primary objective is to evaluate whether the addition of anticoagulation reduces major cardiovascular events without significantly increasing bleeding risk.
In addition to the clinical trial component, the study will incorporate a translational research arm. Peripheral blood samples will be collected to investigate genetic variants and DNA and RNA expression profiles that may be associated with susceptibility to CAE, disease progression, and differential response to antithrombotic therapy. These analyses aim to improve the understanding of the biological mechanisms underlying CAE and to identify potential biomarkers that could inform future personalized treatment strategies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dual Antiplatelet Therapy | Active comparator | Drug: Aspirin 100 mg, Drug: Clopidogrel 75 mgParticipants receive standard dual antiplatelet therapy consisting of aspirin 100 mg once daily plus clopidogrel 75 mg once daily |
| Antiplatelet Monotherapy Plus Oral Anticoagulation | Experimental | Drug: Clopidogrel 75 mg, Drug: Rivaroxaban 15 mgParticipants receive antiplatelet monotherapy with clopidogrel 75 mg once daily plus oral anticoagulation using rivaroxaban 15 mg once daily |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Adults aged 18 to 80 years, of either sex, hospitalized with acute coronary syndrome (ACS) with or without ST-segment elevation.
- Recent ACS within 7 days prior to enrollment, defined by all of the following:
- Clinical presentation consistent with acute coronary syndrome.
- Elevated high-sensitivity cardiac troponin above the 99th percentile.
- Presence or absence of persistent ST-segment elevation.
Key exclusion criteria (8 listed)
- Pregnant women.
- Current indication for temporary or long-term anticoagulation therapy at the time of enrollment.
- Severe chronic kidney disease, defined as KDIGO stage G4 or higher (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m²).
- Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² at hospital discharge.
- History of major bleeding, active bleeding, or high bleeding risk, including but not limited to gastrointestinal bleeding, intracranial hemorrhage, or other conditions considered by the treating physician to confer a high risk of bleeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aspirin 100 mgParticipants receive aspirin 100 mg once daily | Drug | Dual Antiplatelet Therapy |
| Clopidogrel 75 mgParticipants receive clopidogrel 75 mg once daily | Drug | Antiplatelet Monotherapy Plus Oral Anticoagulation, Dual Antiplatelet Therapy |
| Rivaroxaban 15 mgParticipants receive oral anticoagulation using rivaroxaban 15 mg once daily | Drug | Antiplatelet Monotherapy Plus Oral Anticoagulation |
Primary outcome
Time to First Major Adverse Cardiovascular Event (MACE)
Time frame: 12 months
Time to first occurrence of the composite of cardiovascular death, non-fatal myocardial infarction, or repeat coronary revascularization in patients with coronary artery ectasia following acute coronary syndrome, according to the assigned antithrombotic treatment strategy (dual antiplatelet therapy versus clopidogrel plus rivaroxaban).
Time to First Bleeding Event According to the BARC Classification
Time frame: 12 months
Time to first occurrence of a composite of major or minor bleeding events defined according to the Bleeding Academic Research Consortium (BARC) classification in patients with coronary artery ectasia following acute coronary syndrome, according to the assigned antithrombotic treatment strategy (dual antiplatelet therapy versus clopidogrel plus rivaroxaban).
2 secondary outcomes
Individual Components of the Major Adverse Cardiovascular Event Composite
Time frame: 12 months
Individual Bleeding Events According to the BARC Classification
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
- Background: PubMed 40991139Solis-Jimenez F, Esparza XL, Guzman-Solorzano HP, Villalobos-Pedroza M, Morales-Villamil LA, Diaz-Herrera BA, Hernandez-Pastrana S, Gopar-Nieto R, Arias-Sanchez EA, Marroquin-Donday LA, Jimenez-Rodriguez GM, Sierra-Lara D, Araiza-Garaygordobil D, Arias-Mendoza A. Anticoagulant versus Antiplatelet Therapy After Acute Coronary Syndromes in Patients with Coronary Artery Ectasia: A Retrospective Cohort Study. Cardiovasc Drugs Ther. 2026 Jun;40(3):1021-1033. doi: 10.1007/s10557-025-07784-0. Epub 2025 Sep 24.
- Background: PubMed 39615618Araiza-Garaygordobil D, Gopar-Nieto R, Sierra-Lara Martinez JD, Mullasari AS, Belderrain-Morales N, Najera-Rojas NA, Diaz-Herrera BA, Sarabia-Chao V, Alfaro-Ponce DL, Briseno-De la Cruz JL, Ruiz-Beltran M, Martinez-Rios MA, Pina-Reyna Y, Latapi-Ruiz Esparza X, Grimaldo-Gomez FA, Cortina-De la Rosa E, Romero-Arroyo MO, Sierra-Gonzalez de Cossio A, Gonzalez-Pacheco H, Arias-Mendoza A. A randomized trial of antithrombotic therapy in patients with acute coronary syndrome and coronary ectasia. Am Heart J. 2025 Mar;281:103-111. doi: 10.1016/j.ahj.2024.11.012. Epub 2024 Nov 29.
- Background: PubMed 29051141Doi T, Kataoka Y, Noguchi T, Shibata T, Nakashima T, Kawakami S, Nakao K, Fujino M, Nagai T, Kanaya T, Tahara Y, Asaumi Y, Tsuda E, Nakai M, Nishimura K, Anzai T, Kusano K, Shimokawa H, Goto Y, Yasuda S. Coronary Artery Ectasia Predicts Future Cardiac Events in Patients With Acute Myocardial Infarction. Arterioscler Thromb Vasc Biol. 2017 Dec;37(12):2350-2355. doi: 10.1161/ATVBAHA.117.309683. Epub 2017 Oct 19.
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- Individual participant dataSharing planned: Undecided. Some information might be available upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Direccion de Investigación Instituto Nacional de Cardiología contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aspirin 100 mg, Clopidogrel 75 mg and Rivaroxaban 15 mg in people with Coronary Artery Ectasia and Acute Coronary Syndromes (ACS), run by Instituto Nacional de Cardiologia Ignacio Chavez at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Direccion de Investigación Instituto Nacional de Cardiología (+52 5555732911, comite.investigacion@cardiologia.org.mx), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to First Major Adverse Cardiovascular Event (MACE) (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07511257, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.