Pharmacometrics Analysis of Rivaroxaban in Chinese Children Aged Over 2 Years

Children's Hospital of Fudan University60 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

Conditions

Kawasaki Disease Coronary Artery Aneurysm Rivaroxaban Anticoagulant Drugs Pharmacokinetics and Pharmacodynamics

Eligibility

Sex: ALLMin age: 2 YearsMax age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: From baseline to 6 months after rivaroxaban initiation, with scheduled sampling at the first hospitalization

Rivaroxaban-calibrated anti-activated Factor X (FXa) activity

Time frame: From baseline to 6 months after rivaroxaban initiation, with anti-FXa activity measured at the same time points as plasma concentration

Secondary Outcomes

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.

Time frame: 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