Pharmacometrics Analysis of Rivaroxaban in Chinese Children Aged Over 2 Years

Population Pharmacokinetic/Pharmacodynamic Analysis of Rivaroxaban in Chinese Children Aged Over 2 Years With Giant Coronary Artery Aneurysm After Kawasaki Disease

Based on an established Kawasaki disease cohort database, this prospective, single-center, single-arm, observational study will collect clinical data from children aged 2 years and older with giant coronary artery aneurysms after Kawasaki disease who received rivaroxaban treatment. Rivaroxaban plasma concentrations, anti-factor Xa activity levels, and genetic polymorphisms will be measured and analyzed to support the population pharmacokinetic/pharmacodynamic analysis

Study Overview

• Status: Recruiting
• Conditions: Kawasaki Disease; Coronary Artery Aneurysm; Rivaroxaban; Pharmacokinetics and Pharmacodynamics; Anticoagulant Drugs

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Fang Liu, MD; Phone Number: 18017590880; Email: liufang@fudan.edu.cn
• Study Contact Backup: Name: Guangan Dai, MD; Phone Number: 13580762996; Email: gadai24@m.fudan.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Recruiting
      • Children's Hospital of Fudan University
      • Contact: Fang Liu, MD.; Phone Number: 18017590880; Email: liufang@fudan.edu.cn
      • Principal Investigator: Fang Liu, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Children aged ≥2 years with giant coronary artery aneurysms after Kawasaki disease treated with rivaroxaban at the Children's Hospital of Fudan University

Description

Inclusion Criteria:

1. Giant coronary artery aneurysm(s) in any coronary artery after acute stage of Kawasaki disease. Giant coronary artery aneurysm(s) should be confirmed by two-dimensional echocardiography and meet the diagnostic criteria of Z-score ≥10 or coronary artery internal diameter ≥8mm;
2. Anticoagulant with antiplatelet drug therapy for anti-thromboprophylaxis is recommended for the next 6 months;
3. Children aged 2 years to <18 years

Exclusion Criteria:

1. Active bleeding or bleeding risk contraindicating anticoagulant therapy
2. Hypersensitivity or any other contraindications listed in the local labeling for the comparator treatment or experimental treatment
3. Patients participating in clinical trials of other drugs at the same time

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Rivaroxaban; Rivaroxaban as anticoagulant will be administered with antiplatelet drug for long-term antithrombotic treatment, following a model-based optimized dosing regimen. Rivaroxaban plasma concentration and rivaroxaban-calibrated Anti-FXa activity are measured for clinical monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rivaroxaban plasma concentration	Opportunistic blood sampling will be performed at multiple predefined time points based on the principle of sparse sampling. It includes: 1. Day 1, 20 minutes -1 h after the first dose; 2. Day 1, 7±1 h after the first dose; 3. After at least three continuous doses (≥ Day 4): before the scheduled dose at that day, which is defined as the trough concentration; 4. After at least three continuous doses (≥ Day 4): 3±1 h the scheduled dose at that day, which is defined as the peak concentration. And peak and trough concentrations will be re-measured after each dose adjustment	From baseline to 6 months after rivaroxaban initiation, with scheduled sampling at the first hospitalization
Rivaroxaban-calibrated anti-activated Factor X (FXa) activity	Opportunistic blood sampling will be performed at multiple predefined time points based on the principle of sparse sampling. It includes: 1. Day 1, 20 minutes -1 h after the first dose; 2. Day 1, 7±1 h after the first dose; 3. After at least three continuous doses (≥ Day 4): before the scheduled dose at that day, which is defined as the trough concentration; 4. After at least three continuous doses (≥ Day 4): 3±1 h the scheduled dose at that day, which is defined as the peak concentration. And peak and trough concentrations will be re-measured after each dose adjustment	From baseline to 6 months after rivaroxaban initiation, with anti-FXa activity measured at the same time points as plasma concentration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of new thrombosis in coronary arteries	It is binary variable. Every echocardiography conducted during study period will be documented. Researcher will document whether new thrombosis occurs in coronary arteries, and record the number of involved coronary arteries.	From baseline to 6 months after rivaroxaban initiation
Composite of Major bleeding or Clinically relevant non-major bleeding event	It is a binary variable. Researcher will document major bleeding or clinically relevant non-major bleeding events. Major bleeding is defined as 1.Fatal bleeding; 2.Clinically overt bleeding associated with a decrease in Hemoglobin of ≥20 g/L in a 24-h period; 3.Critical site bleeding, such as retroperitoneal, pulmonary, pericardial, intracranial, or otherwise involves the central nervous system; 4.Bleeding that requires an intervention via an invasive procedure; 5.Overt bleeding for which a reversal agent is administered. Clinically relevant non-major bleeding event is defined as 1.Bleeding that results in a medical or procedural intervention not meeting major bleeding criteria, including a medication change (reducing, holding, or changing anticoagulation or addition of new medication) ; 2.Bleeding that results in hospitalization or increased level of care; 3.Overt bleeding for which a blood product is administered, and does not meet the criteria for major bleeding	From baseline to 6 months after rivaroxaban initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic polymorphism	Opportunistic sampling will be performed using the remaining blood specimens collected for rivaroxaban plasma concentration measurement. Genetic polymorphisms related to rivaroxaban metabolism and transport will be examined, including CYP3A4, ABCB1, ABCG2, and et.cl CYP3A4: Cytochrome P450 Family 3 Subfamily A Member 4, ABCB1: ATP Binding Cassette Subfamily B Member 1; ABCG2: ATP Binding Cassette Subfamily G Member 2	Day 1

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Investigators: Study Director: Fang Liu, MD, Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 11, 2025
• First Submitted That Met QC Criteria: May 25, 2025
• First Posted (Actual): May 29, 2025

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 25, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: anticoagulant; rivaroxaban; Kawasaki disease; Coronary artery aneurysm; Population pharmacokinetic and pharmacodynamic
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Skin Diseases; Lymphatic Diseases; Skin Diseases, Vascular; Coronary Disease; Myocardial Ischemia; Vasculitis; Aneurysm; Mucocutaneous Lymph Node Syndrome; Coronary Aneurysm
• Other Study ID Numbers: RIVA-KD-PopPK

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