RECRUITINGPhase 4INTERVENTIONAL
Model-informed Dose Optimization for Rivaroxaban in Children With Giant Coronary Artery Aneurysm After Kawasaki Disease
Rivaroxaban in Chinese Children With Giant Coronary Artery Aneurysm After Kawasaki Disease: a Pilot Study
About This Trial
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.
Who May Be Eligible (Plain English)
Who May Qualify:
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. Participant should be able to tolerate oral feeding, nasogastric or gastric feeding;
4. Children aged 1 Month to\<18 years, bodyweight ≥ 2600g.
Who Should NOT Join This Trial:
1. Active bleeding or bleeding risk contraindicating anticoagulant therapy
2. With history of venous thromboembolism or risk factors related with venous thromboembolism, like congenital heart disease, carcinoma, central venous catheter or long-term immobilization.
3. Hypersensitivity or any other contraindications listed in the local labeling for the comparator treatment or experimental treatment
4. An eGFR \<30 mL/min/1.73 m2 (For children younger than 1 year, serum creatinine results above 97.5th percentile)
5. Platelet count \< 100 x 109/L
6. Hepatic disease which is associated with either: coagulopathy leading to a clinically relevant bleeding risk, or alanine aminotransferase \> 5x ULN or total bilirubin \> 2x ULN with direct bilirubin \> 20% of the total
7. Sustained uncontrolled hypertension defined as systolic and/or diastolic blood pressure \>95 th age percentile
8. Concomitant use of strong inhibitors of both CYP3A4 and P-glycoprotein, including but not limited to all human weakened immune system virus protease inhibitors and the following azole-antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically (fluconazole is allowed)
9. Concomitant use of strong inducers of CYP3A4, including but not limited to rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
...See full criteria on ClinicalTrials.gov
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Original Eligibility Criteria
View original clinical language
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. Participant should be able to tolerate oral feeding, nasogastric or gastric feeding;
4. Children aged 1 Month to\<18 years, bodyweight ≥ 2600g.
Exclusion Criteria:
1. Active bleeding or bleeding risk contraindicating anticoagulant therapy
2. With history of venous thromboembolism or risk factors related with venous thromboembolism, like congenital heart disease, carcinoma, central venous catheter or long-term immobilization.
3. Hypersensitivity or any other contraindications listed in the local labeling for the comparator treatment or experimental treatment
4. An eGFR \<30 mL/min/1.73 m2 (For children younger than 1 year, serum creatinine results above 97.5th percentile)
5. Platelet count \< 100 x 109/L
6. Hepatic disease which is associated with either: coagulopathy leading to a clinically relevant bleeding risk, or alanine aminotransferase \> 5x ULN or total bilirubin \> 2x ULN with direct bilirubin \> 20% of the total
7. Sustained uncontrolled hypertension defined as systolic and/or diastolic blood pressure \>95 th age percentile
8. Concomitant use of strong inhibitors of both CYP3A4 and P-glycoprotein, including but not limited to all human immunodeficiency virus protease inhibitors and the following azole-antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically (fluconazole is allowed)
9. Concomitant use of strong inducers of CYP3A4, including but not limited to rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
10. Hypersensitivity or any other contraindications listed in the local labeling for the comparator treatment or experimental treatment
11. Inability to cooperate with the study procedures and follow-up visits
12. Refuse to provide informed consent
eGFR, estimated glomerular filtration rate; ULN, upper level of normal; TB, total bilirubin (TB); CYP3A4, cytochrome P450 isoenzyme 3A4
Treatments Being Tested
DRUG
Rivaroxaban (Xarelto)
Administered in an age- and bodyweight-adjusted, 15 mg-equivalent dose regimen proposed by model-informed dose optimization study
Locations (1)
Children's Hospital of Fudan University
Shanghai, Shanghai Municipality, China