Anticoagulant Drugs, Coronary Artery Aneurysm, Kawasaki Disease, Pharmacokinetics and Pharmacodynamics, Rivaroxaban
Conditions
Keywords
Kawasaki disease, Coronary artery aneurysm, Population pharmacokinetic and pharmacodynamic, rivaroxaban, anticoagulant
Brief summary
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
Interventions
None listed
Sponsors
Children's Hospital of Fudan University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rivaroxaban plasma concentration | From baseline to 6 months after rivaroxaban initiation, with scheduled sampling at the first hospitalization | 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 |
| Rivaroxaban-calibrated anti-activated Factor X (FXa) activity | From baseline to 6 months after rivaroxaban initiation, with anti-FXa activity measured at the same time points as 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of new thrombosis in coronary arteries | From baseline to 6 months after rivaroxaban initiation | 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. |
| Composite of Major bleeding or Clinically relevant non-major bleeding event | From baseline to 6 months after rivaroxaban initiation | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Genetic polymorphism | Day 1 | 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 |
Countries
China
Contacts
Primary ContactFang Liu, MD
Backup ContactGuangan Dai, MD
Outcome results
None listed