Rivaroxaban for Children Aged Over 2 Years With Giant Coronary Artery Aneurysms After Kawasaki Disease
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age2-18
SponsorChildren's Hospital of Fudan University
About this trial
Based on population pharmacokinetic model-based simulation, a 15 mg-equivalent, age-, and bodyweight-adjusted dosing regimen for Chinese children with giant coronary artery aneurysms after acute Kawasaki disease was proposed. This exploratory trial aims to evaluate the feasibility, safety and effectiveness of rivaroxaban compared to warfarin for thromboprophylaxis in children aged over 2 years with giant coronary artery aneurysms after Kawasaki disease
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 3 months;
Participant should be able to tolerate oral feeding, nasogastric or gastric feeding;
Children aged ≥ 2 years
Disqualifiers
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.
Thrombus within giant coronary aneurysm was confirmed by previous imaging examinations, including two-dimensional echocardiography, computed tomography angiography in coronary artery or coronary angiography
An eGFR <30mL/min/1.73 m2 (For children younger than 1 year, serum creatinine results above 97.5th percentile)
Trial design
Design model
Parallel
Treatments tested in this trial
Rivaroxaban Oral Tablet [Xarelto]
DrugAdministered in an age- and bodyweight-adjusted, 15 mg-equivalent dose regimen proposed by model- and clinical evidence-informed precision dosing
Aspirin or Clopidogrel
DrugAspirin \[3 \~5mg/(kg·d) once daily\] or Clopidogrel \[1.0 mg/kg; once daily\]
Warfarin
DrugWarfarin 0.05\~0.12 mg/(kg·d) once daily. INR should maintain within 1.5 to 2.5
Treatment groups
100 Participants
are divided into 2 treatment groupsGroup A: Rivaroxaban+Antiplatelet drugExperimental treatment 2 interventions
Group B: Standard antithrombotic careActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Composite of new thrombosis in coronary arteries, major bleeding, clinically relevant non-major bleeding event or major adverse cardiovascular event
It is a binary variable. This composite outcome indicates whether any of the following events occurred within 3 months after treatment initiation: (a) newly developed coronary artery thrombosis; (b) major bleeding event; (c) clinically relevant non-major bleeding event; or (d) major adverse cardiovascular event (defined as unstable angina, acute myocardial infarction, hospitalization for heart failure, unplanned coronary revascularization, stroke, or cardiovascular death).
Time frame
From Day 1 of treatment to the third month after treatment initiationSecondary outcomes
1
Occurrence of new thrombosis in coronary arteries
It is binary data. Every echocardiography conducted during study period will be assessed by masked sonographer. The masked sonographers will assess whether new thrombosis occurs in coronary arteries, and recorded the number of involved coronary arteries.
Time frame
From Day 1 of treatment to the third month after treatment initiation2
Time to first new thrombosis in coronary arteries
It is time to event data. Every echocardiography conducted during study period will be assessed by masked sonographer. The masked sonographers will assess whether new thrombosis occurs in coronary arteries, and recorded the time to first new thrombosis in coronary arteries.
Time frame
From Day 1 of treatment to the third month after treatment initiation3
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
Time frame
From Day 1 of treatment to the third month after treatment initiation4
Occurrence of major bleeding
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.
Time frame
From Day 1 of treatment to the third month after treatment initiationOther outcomes
1
Genetic polymorphism
For experimental group, the rest blood sample from rivaroxaban plasma concentration measurement will be collected for genetic polymorphisms examination. Genes 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
Time frame
From Day 1 of treatment to the third month after treatment initiationSponsors and contacts
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Source ClinicalTrials.gov