Efficacy and Safety of Rivaroxaban in the Early Postoperative Period for Patients With Bioprosthetic Valves

Efficacy and Safety of Rivaroxaban in the Early Postoperative Period for Patients With Bioprosthetic Valves: A Prospective, Randomized, Controlled Non-Inferiority Trial

this study aims to comprehensively evaluate the efficacy and safety profiles of rivaroxaban and warfarin during the initial postoperative period following surgical bioprosthetic valve in patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Anticoagulation
• Intervention / Treatment: Drug: Rivaroxaban

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bo Xie; Phone Number: 021-68383761; Email: xieborj@hotmail.com
• Study Contact Backup: Name: Xin Wang; Phone Number: 13052395835; Email: 15656594127@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged between 18 and 80 years
• Patients who underwent successful surgical bioprosthetic valve replacement or repair to either the mitral, aortic position or both
• Signed informed consent

Exclusion Criteria:

• Aged below 18 or over 80 years
• Mechanical heart valves (MHV)
• Bioprosthetic valve transcatheter valve replacement (TAVR)

• Hemorrhage risk-related criteria

  1. Active internal bleeding
  2. Major surgical procedure or trauma within 30 days before the randomization visit
  3. History of intracranial, intraocular, spinal, gastrointestinal, or atraumatic intra-articular bleeding
  4. Chronic hemorrhagic disorder
  5. Planned invasive procedure with potential for uncontrolled bleeding, including major surgery

• Concomitant conditions and therapies

  1. Clinically overt stroke within the past 3 months
  2. Major surgery within 1 month
  3. Acute coronary syndrome within 1 month
  4. Active infective endocarditis
  5. Severe hepatic impairment、hepatic disease associated with coagulopathy or Moderate and severe hepatic impairment (Child-Pugh Class B or C)
  6. Uncontrolled severe hypertension
  7. Active malignancy

• Medication-related

  1. Hypersensitivity or contraindications to Rivaroxaban, VKA, heparin.
  2. Concomitant treatment with strong inhibitors of both CYP3A4 and P-gp (e.g., azole antifungals, such as ketoconazole and itraconazole, or HIV protease inhibitors, such as ritonavir)
  3. Concomitant treatment with strong inducers of CYP3A4 (e.g., carbamazepine, phenytoin, rifampin, etc.)
• HAS-BLED score>3

• Others

  1. Abnormal local laboratory results, such as Platelet count < 50 x109/L、Hemoglobin < 8 g/dL (5 mmol/L)
  2. Female subjects of childbearing potential without using adequate contraception、
  3. Female pregnant or breast-feeding
  4. Participation is not likely to comply with the study procedures or will complete follow-up
  5. Participation in another clinical trial that potentially interferes with the current study
  6. Life expectancy less than 6 months beyond the targeted last visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: warfarin group; A 3-6-month anticoagulation therapy with warfarin is recommended after the BPV surgery. Patients allocated to the warfarin group will adhere to a target INR range of 2 to 3. Patients 65 > years old and low weight should take warfarin 2.5mg/day and all other patients should take 5mg/day. During hospitalization, the INR will be reassessed daily, and regular measurements (at least every four weeks) should be conducted post-discharge to ensure ongoing patient stability.
Experimental: rivaroxaban group; Patients allocated to the rivaroxaban group will be administered a dose of 20 mg orally once daily (to be taken with food), or 15 mg once daily in patients with moderate renal impairment at screening (defined as creatinine clearance rate, CrCl between 30 and 49 mL/min).	Drug: Rivaroxaban; To compare the efficacy and safety of rivaroxaban as an early anticoagulant therapy for BPV patients with the traditional postoperative anticoagulant warfarin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
all-cause death	Patients will be scheduled for outpatient clinic or phone visits at intervals of 0.5, 1, 3, and 6 months following enrollment. During these visits, patients will be instructed to document any symptoms indicative of clinical thromboembolic or bleeding events. If such symptoms are reported, patients may undergo necessary diagnostic and laboratory testing. Cardiac CT and transthoracic echocardiography will be conducted at the 3-month and 6-month marks post-randomization.	0.5, 1, 3, and 6 months
Major cardiovascular events (stroke, transient ischemic attack (TIA), valve thrombosis, systemic embolism not related to the central nervous system (CNS), hospitalization due to heart failure)	Patients will be scheduled for outpatient clinic or phone visits at intervals of 0.5, 1, 3, and 6 months following enrollment. During these visits, patients will be instructed to document any symptoms indicative of clinical thromboembolic or bleeding events. If such symptoms are reported, patients may undergo necessary diagnostic and laboratory testing. Cardiac CT and transthoracic echocardiography will be conducted at the 3-month and 6-month marks post-randomization.	0.5, 1, 3, and 6 months
Major bleeding	Patients will be scheduled for outpatient clinic or phone visits at intervals of 0.5, 1, 3, and 6 months following enrollment. During these visits, patients will be instructed to document any symptoms indicative of clinical thromboembolic or bleeding events. If such symptoms are reported, patients may undergo necessary diagnostic and laboratory testing. Cardiac CT and transthoracic echocardiography will be conducted at the 3-month and 6-month marks post-randomization.	0.5, 1, 3, and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thromboembolic events (stroke, TIA, deep venous thrombosis, pulmonary embolism, non-CNS systemic embolism, valve thrombosis).	The Efficacy endpoint was defined as the composite of death from cardiovascular causes or Patients will be scheduled for outpatient clinic or phone visits at intervals of 0.5, 1, 3, and 6 months following enrollment. During these visits, patients will be instructed to document any symptoms indicative of clinical thromboembolic or bleeding events. If such symptoms are reported, patients may undergo necessary diagnostic and laboratory testing. Cardiac CT and transthoracic echocardiography will be conducted at the 3-month and 6-month marks post-randomization.	0.5, 1, 3, and 6 months
Cardiovascular causes death	Patients will be scheduled for outpatient clinic or phone visits at intervals of 0.5, 1, 3, and 6 months following enrollment. During these visits, patients will be instructed to document any symptoms indicative of clinical thromboembolic or bleeding events. If such symptoms are reported, patients may undergo necessary diagnostic and laboratory testing. Cardiac CT and transthoracic echocardiography will be conducted at the 3-month and 6-month marks post-randomization.	0.5, 1, 3, and 6 months
Major bleeding events and clinically relevant non-major (CRNM) bleeding events and minor bleeding events	Patients will be scheduled for outpatient clinic or phone visits at intervals of 0.5, 1, 3, and 6 months following enrollment. During these visits, patients will be instructed to document any symptoms indicative of clinical thromboembolic or bleeding events. If such symptoms are reported, patients may undergo necessary diagnostic and laboratory testing. Cardiac CT and transthoracic echocardiography will be conducted at the 3-month and 6-month marks post-randomization.	0.5, 1, 3, and 6 months

Collaborators and Investigators

• Sponsor: RenJi Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: June 20, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Estimated): June 28, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: warfarin; anticoagulation; rivaroxaban; Bioprosthetic valve
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: IIT-2023-0325

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No