Effects of Rivaroxaban on Vascular FMD in Patients With Stable Atherosclerotic Vascular Diseases

NCT06986369 | Completed Phase 4 DMC

• 1 other identifier: UW 20-312
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

The specific mechanistic benefit of rivaroxaban versus other FXa inhibitors on atherothrombotic events remain unclear. Therefore plan to initiate a prospective, randomized study to investigate the effect of rivaroxaban and aspirin versus aspirin alone on changes of number circulating endothelial cells and endothelial function, and alteration in systemic inflammation, platelet and coagulation activation in patients with stable atherosclerotic vascular diseases. The working hypothesis of this trial is that rivaroxaban and aspirin is superior to aspirin alone improvement in the number of circulating endothelial cells and endothelial function, assessed by flow-mediated vasodilatation, and reduction in systemic inflammation, platelet and coagulation activation in patients with stable atherosclerotic vascular diseases at 3 months follow-up.

Conditions

Atherosclerosis, Coronary

Outcome Measures

Primary Outcomes (1)

• Endothelial Function

  The Flow mediated dilatation of brachial artery at the baseline and the 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 (2)

• Plasma Adenosine Level Platelet Function Parameter Endothelial Progenitor Cell Count Biomarkers such as Highly Sensitive Troponin.

  3 months

• Platelet function parameter and Coagulation parameter

  3 months

Study Arms (2)

rivaroxaban 2.5mg twice daily and aspirin 100mg once daily

ACTIVE COMPARATOR

Rivaroxaban 2.5mg twice daily Oral Tablet novel oral anticoagulants , 2.5mg twice daily for 3 months and Aspirin 100 MG Oral Tablet, Enteric Coated antiplatelet agent, 100mg once daily for 3 months

Drug: Rivaroxaban 2.5 MG Oral Tablet [Xarelto]

Aspirin 100mg daily for 3 months

NO INTERVENTION

Aspirin 100 MG Oral Tablet, Enteric Coated antiplatelet agent, 100mg once daily for 3 months

Interventions

Rivaroxaban 2.5 MG Oral Tablet [Xarelto] DRUG

prospective, randomized, 3 months study to clarify the efficacy of rivaroxaban and aspirin versus aspirin in the alone the changes on the number of circulating endothelial cells and endothelial function, and systemic inflammation, platelet and coagulation activation in patients with stable atherosclerotic vascular diseases.

Also known as: Xarelto

rivaroxaban 2.5mg twice daily and aspirin 100mg once daily

Eligibility Criteria

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

You may qualify if:

• patients must fulfill the following criteria.
• Willing and able to provide written informed consent
• CAD and/or PAD
• Subjects with CAD must also meet at least 1 of the following criteria:
• Age 65 years or older, or Age younger than 65 years and documented atherosclerosis or revascularization involving at least 2 vascular beds or at least 2 additional risk factors:
• Current smoker (within 1 year of randomization)
• Diabetes mellitus
• Renal dysfunction with estimated glomerular filtration rate \< 60 mL/min
• Heart failure
• Non-lacunar ischemic stroke \>/= 1 month ago

You may not qualify if:

• High risk of bleeding
• Stroke within 1 month or any history of hemorrhagic or lacunar stroke
• Severe heart failure with known ejection fraction \< 30% or New York Heart Association class III or IV symptoms
• Estimated glomerular filtration rate \< 15 mL/min
• Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy, or oral anticoagulant therapy
• Known non-cardiovascular disease that is associated with poor prognosis (eg, metastatic cancer) or that increases the risk of an adverse reaction to study interventions
• History of hypersensitivity or known contraindication for rivaroxaban, aspirin, pantoprazole, or excipients, if applicable
• Systemic treatment with strong inhibitors of CYP3A4 as well as p-glycoprotein (eg, systemic azole antimycotics, such as ketoconazole, and HIV-protease inhibitors, such as ritonavir), or strong inducers of CYP 3A4 (ie, rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine)
• Any known hepatic disease associated with coagulopathy
• Subjects who are pregnant, breastfeeding, or are of childbearing potential, and sexually active and not practicing an effective method of birth control (eg, surgically sterile, prescription oral contraceptives, contraceptive injections, intrauterine device, double- barrier method, contraceptive patch, male partner sterilization)
• Previous assignment to treatment during this study
• Concomitant participation in another study with investigational drug
• Known contraindication to any study-related procedures

Sponsors & Collaborators

• The University of Hong Kong: lead
• Bayer: collaborator

Study Sites (1)

Queen Mary Hospital, the University of Hong Kong

Hong Kong, China

Location

Related Publications (14)

• Borissoff JI, Spronk HM, ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med. 2011 May 5;364(18):1746-60. doi: 10.1056/NEJMra1011670. No abstract available.

  PMID: 21542745 BACKGROUND

• Spronk HM, de Jong AM, Crijns HJ, Schotten U, Van Gelder IC, Ten Cate H. Pleiotropic effects of factor Xa and thrombin: what to expect from novel anticoagulants. Cardiovasc Res. 2014 Mar 1;101(3):344-51. doi: 10.1093/cvr/cvt343. Epub 2014 Jan 2.

  PMID: 24385341 BACKGROUND

• Esmon CT. Targeting factor Xa and thrombin: impact on coagulation and beyond. Thromb Haemost. 2014 Apr 1;111(4):625-33. doi: 10.1160/TH13-09-0730. Epub 2013 Dec 12.

  PMID: 24336942 BACKGROUND

• Eriksson BI, Quinlan DJ, Eikelboom JW. Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism. Annu Rev Med. 2011;62:41-57. doi: 10.1146/annurev-med-062209-095159.

  PMID: 21226611 BACKGROUND

• Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, Bhatt DL, Goodman S, Verheugt FW, Flather M, Huber K, Liaw D, Husted SE, Lopez-Sendon J, De Caterina R, Jansky P, Darius H, Vinereanu D, Cornel JH, Cools F, Atar D, Leiva-Pons JL, Keltai M, Ogawa H, Pais P, Parkhomenko A, Ruzyllo W, Diaz R, White H, Ruda M, Geraldes M, Lawrence J, Harrington RA, Wallentin L; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011 Aug 25;365(8):699-708. doi: 10.1056/NEJMoa1105819. Epub 2011 Jul 24.

  PMID: 21780946 BACKGROUND

• Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, Burton P, Cohen M, Cook-Bruns N, Fox KA, Goto S, Murphy SA, Plotnikov AN, Schneider D, Sun X, Verheugt FW, Gibson CM; ATLAS ACS 2-TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. doi: 10.1056/NEJMoa1112277. Epub 2011 Nov 13.

  PMID: 22077192 BACKGROUND

• Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, Widimsky P, Hori M, Avezum A, Piegas LS, Branch KRH, Probstfield J, Bhatt DL, Zhu J, Liang Y, Maggioni AP, Lopez-Jaramillo P, O'Donnell M, Kakkar AK, Fox KAA, Parkhomenko AN, Ertl G, Stork S, Keltai M, Ryden L, Pogosova N, Dans AL, Lanas F, Commerford PJ, Torp-Pedersen C, Guzik TJ, Verhamme PB, Vinereanu D, Kim JH, Tonkin AM, Lewis BS, Felix C, Yusoff K, Steg PG, Metsarinne KP, Cook Bruns N, Misselwitz F, Chen E, Leong D, Yusuf S; COMPASS Investigators. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017 Oct 5;377(14):1319-1330. doi: 10.1056/NEJMoa1709118. Epub 2017 Aug 27.

  PMID: 28844192 BACKGROUND

• Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F, Metsarinne K, O'Donnell M, Dans AL, Ha JW, Parkhomenko AN, Avezum AA, Lonn E, Lisheng L, Torp-Pedersen C, Widimsky P, Maggioni AP, Felix C, Keltai K, Hori M, Yusoff K, Guzik TJ, Bhatt DL, Branch KRH, Cook Bruns N, Berkowitz SD, Anand SS, Varigos JD, Fox KAA, Yusuf S; COMPASS investigators. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018 Jan 20;391(10117):205-218. doi: 10.1016/S0140-6736(17)32458-3. Epub 2017 Nov 10.

  PMID: 29132879 BACKGROUND

• Anand SS, Bosch J, Eikelboom JW, Connolly SJ, Diaz R, Widimsky P, Aboyans V, Alings M, Kakkar AK, Keltai K, Maggioni AP, Lewis BS, Stork S, Zhu J, Lopez-Jaramillo P, O'Donnell M, Commerford PJ, Vinereanu D, Pogosova N, Ryden L, Fox KAA, Bhatt DL, Misselwitz F, Varigos JD, Vanassche T, Avezum AA, Chen E, Branch K, Leong DP, Bangdiwala SI, Hart RG, Yusuf S; COMPASS Investigators. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018 Jan 20;391(10117):219-229. doi: 10.1016/S0140-6736(17)32409-1. Epub 2017 Nov 10.

  PMID: 29132880 BACKGROUND

• Alvarez E, Paradela-Dobarro B, Raposeiras-Roubin S, Gonzalez-Juanatey JR. Protective, repairing and fibrinolytic effects of rivaroxaban on vascular endothelium. Br J Clin Pharmacol. 2018 Feb;84(2):280-291. doi: 10.1111/bcp.13440. Epub 2017 Oct 25.

  PMID: 28940408 BACKGROUND

• Lee IO, Kratz MT, Schirmer SH, Baumhakel M, Bohm M. The effects of direct thrombin inhibition with dabigatran on plaque formation and endothelial function in apolipoprotein E-deficient mice. J Pharmacol Exp Ther. 2012 Nov;343(2):253-7. doi: 10.1124/jpet.112.194837. Epub 2012 Jul 25.

  PMID: 22837011 BACKGROUND

• Borissoff JI, Otten JJ, Heeneman S, Leenders P, van Oerle R, Soehnlein O, Loubele ST, Hamulyak K, Hackeng TM, Daemen MJ, Degen JL, Weiler H, Esmon CT, van Ryn J, Biessen EA, Spronk HM, ten Cate H. Genetic and pharmacological modifications of thrombin formation in apolipoprotein e-deficient mice determine atherosclerosis severity and atherothrombosis onset in a neutrophil-dependent manner. PLoS One. 2013;8(2):e55784. doi: 10.1371/journal.pone.0055784. Epub 2013 Feb 7.

  PMID: 23409043 BACKGROUND

• Ragosta M, Gimple LW, Gertz SD, Dunwiddie CT, Vlasuk GP, Haber HL, Powers ER, Roberts WC, Sarembock IJ. Specific factor Xa inhibition reduces restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits. Circulation. 1994 Mar;89(3):1262-71. doi: 10.1161/01.cir.89.3.1262.

  PMID: 8124815 BACKGROUND

• Borissoff JI, Heeneman S, Kilinc E, Kassak P, Van Oerle R, Winckers K, Govers-Riemslag JW, Hamulyak K, Hackeng TM, Daemen MJ, ten Cate H, Spronk HM. Early atherosclerosis exhibits an enhanced procoagulant state. Circulation. 2010 Aug 24;122(8):821-30. doi: 10.1161/CIRCULATIONAHA.109.907121. Epub 2010 Aug 9.

  PMID: 20697022 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Rivaroxaban; Tablets

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Hung Fat Tse

  Queen Mary Hospital, Hong Kong

  PRINCIPAL INVESTIGATOR

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: rivaroxaban and aspirin versus aspirin alone

Study Record Dates

• First Submitted: March 7, 2024
• First Posted: May 23, 2025
• Study Start: May 4, 2021
• Primary Completion: August 28, 2023
• Study Completion: March 1, 2024
• Last Updated: May 23, 2025

Record last verified: 2025-05

Locations

CN (1)