Based on a population pharmacokinetic model-based dose optimization study, a 15 mg-equivalent, age-, and bodyweight-adjusted dosing regimen for Chinese children with giant coronary artery aneurysms after Kawasaki disease was proposed. This single-center, single-arm, pilot study aims to evaluate the feasibility of the 15 mg-equivalent dosing regimen within a limited sample size.
Patients will be followed for more than 6 months. Clinical outcomes, including coronary artery thrombosis, major adverse cardiovascular events, and bleeding events, will be recorded. Rivaroxaban levels will be measured to assess the robustness of the model-informed dose optimization.
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;
Anticoagulant with antiplatelet drug therapy for anti-thromboprophylaxis is recommended for the next 6 months;
Participant should be able to tolerate oral feeding, nasogastric or gastric feeding;
Children aged 1 Month to<18 years, bodyweight ≥ 2600g.
Active bleeding or bleeding risk contraindicating anticoagulant therapy
With history of venous thromboembolism or risk factors related with venous thromboembolism, like congenital heart disease, carcinoma, central venous catheter or long-term immobilization.
Hypersensitivity or any other contraindications listed in the local labeling for the comparator treatment or experimental treatment
An eGFR <30 mL/min/1.73 m2 (For children younger than 1 year, serum creatinine results above 97.5th percentile)
Single group
Rivaroxaban (Xarelto)
DrugAdministered in an age- and bodyweight-adjusted, 15 mg-equivalent dose regimen proposed by model-informed dose optimization study
Occurrence of new thrombosis in coronary arteries
It is a binary variable. Every echocardiography conducted during study period will be assessed and documented. Investigators will evaluate whether new thrombosis occurs in coronary arteries.
Composite of Major bleeding or Clinically relevant non-major bleeding event
It is a binary variable. Major bleeding is defined as 1.Fatal bleeding; 2.Clinically overt bleeding associated with a decrease in Hgb of ≥20 g/L (2 g/dL) 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
Occurrence of major adverse cardiovascular event
It is a binary variable. Major adverse cardiovascular event (MACE) includes unstable angina, acute myocardial infarction, stroke, hospitalization for heart failure, unplanned revascularization, cardiovascular death. If any of the MACEs occur during the study period, it will be recorded as 1; otherwise, it will be recorded as 0. The definition of each MACE refers to the following guidelines and consensus: 2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials, 2019 European Society of Cardiology Guidelines for the diagnosis and management of chronic coronary syndromes, Fourth universal definition of myocardial infarction, and 2023 European Society of Cardiology Guidelines for the management of acute coronary syndromes.
Any adverse events
It is a text variable. If any adverse events( including durg allergy, severe infection, hepatic dysfunction, renal dysfunction, hypertension, fatigue, abdominal pain or others) occur will be reported to the data and safety monitoring board. The detail of adverse event will be recorded, including classification of adverse event, time of occurrence, symptoms, treatment, resolution time, and outcome.
Any dose adjustments for rivaroxaban
It is a text variable. Any dose adjustments for rivaroxaban will be recorded, including time of dose adjustment, reason for dose adjustment, dosage, and outcome. Rivaroxaban plasma concentration and rivaroxaban-calibrated anti-factor Xa activity will be measured after at least 3 consecutive doses
Plasma concentration of rivaroxaban at specific timepoint
Rivaroxaban plasma concentration will be measured by high performance liquid chromatography tandem mass spectrometer at specific timepoint. It includes 1. 20 minutes to 1 hour after the first dose; 2. 7 ± 1 hours after the first dose; 3. Ctrough: before the scheduled dose after at least three consecutive doses; 4. Cmax: 3 ± 1 hours after at least three consecutive doses. And Ctrough and Cmax will be re-measured after each dose adjustment.
Rivaroxaban-calibrated anti-factor Xa activity at specific timepoint
Rivaroxaban-calibrated anti-factor Xa activity will be measured at specific timepoint. It includes 1. 20 minutes to 1 hour after the first dose; 2. 7 ± 1 hours after the first dose; 3. Ctrough: before the scheduled dose after at least three consecutive doses; 4. Cmax: 3 ± 1 hours after at least three consecutive doses. And Ctrough and Cmax will be re-measured after each dose adjustment.
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