VTE Incidence After Rivaroxaban + Aspirin or SAPT After Lower-limb Revascularization (RESOLUTION)

Incidence of Venous Thromboembolism After Lower Limb Revascularization in Patients Receiving Rivaroxaban 2.5 Mg Bid + Aspirin 100 Mg Versus Single Antiplatelet Treatment - a Randomized Clinical Trial

Venous thromboembolism (VTE) has a high prevalence in patients with multiple comorbidities undergoing complex surgical procedures. Sometimes, extended prophylaxis for VTE with KLMWH or direct oral anticoagulants (DOACs) is necessary. Currently, there is no consensus in the literature regarding the use of DOACs for extended VTE prophylaxis in patients undergoing lower limb revascularization (LLR). Objective: To evaluate the use of DOACs (already approved to reduce MACE and MALE) in VTE prophylaxis in patients undergoing LLR.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Peripheral Arterial Disease; Venous Thormboembolism; Vascular Surgery Patient with PAD / Carotid Stenosis
• Intervention / Treatment: Drug: rivaroxaban 2.5 mg bid + aspirin 100 mg; Drug: clopidogrel 75 mg od for 3 months followed by aspirin 100 mg od for endovascular procedures or aspirin for open procedures

Detailed Description

The goal of this clinical trial is to evaluate the 30-day VTE incidence in patients submitted to endovascular or open surgery for lower limbs revascularization treated with either rivaroxaban 2.5 mg bid + aspirin 100 mg or single antiplatelet agents (SoC). The main questions it aims to answer are:

Does rivaroxaban 2.5 mg + aspirin reduce the incidence of 30-day VTE?

Researchers will compare rivaroxaban 2.5 mg bid + aspirin 100 mg to a single antiplatelet agent to check comparative VTE incidence.

Participants will:

Take either rivaroxaban 2.5 mg bid + aspirin continuously or single antiplatelet agent (clopidogrel for 3 months followed by aspirin 100 mg for endovascular procedures or aspirin for oper procedures) Visit the clinic once every 2 weeks for checkups and tests, and a mandatory Doppler ultrasound at day 30 Keep a diary of their symptoms

Study Population The study population will consist of patients hospitalized in the vascular surgery ward at the Hospital das Clínicas/Brazilian Hospital Services Company-Federal University of Pernambuco (HC/EBSERH-UFPE) who undergo arterial revascularization surgery of the lower limbs (LL) via angioplasty (ATP) or bypass surgery.

The study will determine the sample size by the criteria established by Resolution 466/12 of the National Health Council. The estimated sample size is 200 research participants, with 100 in the study group and 100 in the control group. If the degree of dispersion is high, the number of research participants may be adjusted.

Study Design A single-center randomized clinical trial. Randomization will be performed using the REDCap platform. Due to the nature of the procedure, blinding will not be possible.

Considering an acceptable margin of error (5%), a confidence level of 95%, and a prevalence of 50% for venous diseases, with a heterogeneity level of 50%.

Selection of Research Participants The selection of research participants will follow specific inclusion and exclusion criteria. After selection, participants will be randomly assigned to the Study Group (SG) or the Control Group (CG).

CG (Control Group): Will receive standard treatment as described in the literature: Aspirin (ASA) 100 mg once daily for patients undergoing lower limb bypass revascularization, and ASA 100 mg once daily combined with Clopidogrel 75 mg once daily for patients undergoing lower limb angioplasty.

SG (Study Group): Will receive ASA 100 mg once daily plus Rivaroxaban 2.5 mg twice daily for patients undergoing bypass or angioplasty revascularization.

A total of 100 patients will be included in the study, equally divided between the control and study groups. Randomization will be performed via the REDCap platform.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gabriela Oliveira Buril, MD; Phone Number: +5581991121872; Email: gabriela.buril@ufpe.br

Study Locations

• Brazil
  • PE
    • Pernambuco, PE, Brazil, 50740-900
      • Recruiting
      • Hospital das Clínicas, Federal University of Pernambuco
      • Contact: Gabriela Oliveira Buril, MD; Phone Number: +5581991121872; Email: gabriela.buril@ufpe.br
      • Contact: Gabriela Oliveira Buril, MD
      • Contact: Eduardo Ramacciotti, MD, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be adults of any age and gender.
2. Have critical limb ischemia with a proposed revascularization treatment (either via ATP or bypass surgery) at the Vascular Surgery Service of HC/EBSERH - UFPE.
3. Sign the informed consent form (ICF) (Appendix 2).

Exclusion Criteria:

1. Experience a symptomatic VTE event during hospitalization, as they will require full anticoagulation rather than prophylactic anticoagulation.
2. Have any contraindications to Rivaroxaban.
3. Do not return for the 30-day postoperative follow-up visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: study arm; Rivaroxaban 2.5 mg bid + aspirin 100 mg	Drug: rivaroxaban 2.5 mg bid + aspirin 100 mg; rivaroxaban 2.5 mg bid + aspirin
Active Comparator: comparator; clopidogrel 75 mg od for 3 months followed by aspirin 100 mg od for endovascular procedures or aspirin for open procedures	Drug: clopidogrel 75 mg od for 3 months followed by aspirin 100 mg od for endovascular procedures or aspirin for open procedures; comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
primary efficacy outcome	Incidence of symptomatic + asymptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) 30 days post-hospital discharge.	30 days
primary safety outcome	Combination of clinically relevant non-major bleeding + major bleeding defined by the ISTH criteria	30 days

Collaborators and Investigators

• Sponsor: Science Valley Research Institute
• Investigators: Study Director: Eduardo Ramacciotti, MD, Ph.D., Science Valley

Publications and helpful links

General Publications

• Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, Samama CM. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e227S-e277S. doi: 10.1378/chest.11-2297. Erratum In: Chest. 2012 May;141(5):1369.
• Bonaca MP, Bauersachs RM, Anand SS, Debus ES, Nehler MR, Patel MR, Fanelli F, Capell WH, Diao L, Jaeger N, Hess CN, Pap AF, Kittelson JM, Gudz I, Matyas L, Krievins DK, Diaz R, Brodmann M, Muehlhofer E, Haskell LP, Berkowitz SD, Hiatt WR. Rivaroxaban in Peripheral Artery Disease after Revascularization. N Engl J Med. 2020 May 21;382(21):1994-2004. doi: 10.1056/NEJMoa2000052. Epub 2020 Mar 28.
• 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, Störk 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. Copy
• Haykal T, Zayed Y, Kerbage J, Deliwala S, Long CA, Ortel TL. Meta-analysis and systematic review of randomized controlled trials assessing the role of thromboprophylaxis after vascular surgery. J Vasc Surg Venous Lymphat Disord. 2022 May;10(3):767-777.e3. doi: 10.1016/j.jvsv.2021.08.019. Epub 2021 Sep 8.
• Dagher NN, Modrall JG. Pharmacotherapy before and after revascularization: anticoagulation, antiplatelet agents, and statins. Semin Vasc Surg. 2007 Mar;20(1):10-4. doi: 10.1053/j.semvascsurg.2007.02.006.
• Chindamo MC, Marques MA. Bleeding risk assessment for venous thromboembolism prophylaxis. J Vasc Bras. 2021 Apr 28;20:e20200109. doi: 10.1590/1677-5449.200109.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2024
• Primary Completion (Estimated): July 20, 2025
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: March 6, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Deep Vein Thrombosis; venous thromboembolism; Peripheral Arterial Disease; rivaroxaban; Factor Xa Inhibitors; chronic limb-threatening ischemia
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Embolism and Thrombosis; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Carotid Artery Diseases; Thromboembolism; Cardiovascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Carotid Stenosis; Venous Thromboembolism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Protease Inhibitors; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Clopidogrel; Rivaroxaban; Aspirin
• Other Study ID Numbers: CAAE: 77069024.9.0000.8807 (Other Identifier: Science Valley)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized participant data can be made available upon requests directed to the corresponding author. Proposals will be reviewed based on scientific merit. After a proposal is approved, data can be shared through a secure online platform after signing a data access agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No