Rivaroxaban for Children Aged Over 2 Years With Giant Coronary Artery Aneurysms After Kawasaki Disease

NCT ID: NCT05643651

Last Updated: 2025-07-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2027-09-01

Brief Summary

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

Detailed Description

Lifelong anticoagulant treatment is required in children with giant coronary artery aneurysm after Kawasaki disease, imposing social and psychologic burdens on patients and parents. Rivaroxaban is a potential oral anticoagulant in this population. Considering the impact of ethnic difference and growth development, we proposed a Chinese-specific, optimized dosing regimen based on model- and clinical evidence-informed precision dosing. In the previous pilot study, this optimized dosing regimen demonstrated a favorable feasibility among 11 Chinese pediatric patients aged over 2 years with giant coronary artery aneurysm after Kawasaki disease, with no thrombosis or major bleeding over 6 months.

This study is a multicenter, open-label, exploratory, randomized controlled trial to evaluate the feasibility, safety and effectiveness of rivaroxaban for thromboprophylaxis in children aged over 2 years with giant coronary artery aneurysms after Kawasaki disease, following the 15 mg-equivalent dosing regimen. Participants will be randomly assigned to the control or experimental groups. Randomization ratio will be 2:1. The control group will receive warfarin plus aspirin or clopidogrel, and the experimental group will receive rivaroxaban plus aspirin or clopidogrel. Baseline characteristics, treatment effect outcomes, bleeding events, adverse events and compliance of intervention of each participant will be collected.

Because this is an exploratory study and the low incidence of giant coronary artery aneurysm in children with Kawasaki disease, the study plans to recruit 100 participants. The aims include:

• The feasibility
• The safety and efficacy profile of the optimized, 15 mg-equivalent dosing regimen
• The group differences in safety and treatment effect between warfarin and rivaroxaban

Conditions

Kawasaki Disease; Coronary Artery Aneurysm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Rivaroxaban+Antiplatelet drug

Rivaroxaban as anticoagulant will be administered with antiplatelet drug for 3 months. Antiplatelet drug can choose Aspirin or Clopidogrel depending on participant medical history and physician's recommendation.

Group Type: EXPERIMENTAL

Rivaroxaban Oral Tablet [Xarelto]

Intervention Type: DRUG

Administered in an age- and bodyweight-adjusted, 15 mg-equivalent dose regimen proposed by model- and clinical evidence-informed precision dosing

Aspirin or Clopidogrel

Intervention Type: DRUG

Aspirin \[3 \~5mg/(kg·d) once daily\] or Clopidogrel \[1.0 mg/kg; once daily\]

Standard antithrombotic care

Warfarin as anticoagulant will be administered with antiplatelet drug for 3 months. Antiplatelet drug can choose Aspirin or Clopidogrel depending on participant medical history and physician's recommendation. International normalized ratio(INR) should be tested once a month and maintained in target range(1.5~2.5).

2.Aspirin[3 ~5mg/(kg·d), once daily] or Clopidogrel[ 1.0 mg/kg; once daily] according to experienced clinician recommendation and individual condition.

Group Type: ACTIVE_COMPARATOR

Aspirin or Clopidogrel

Intervention Type: DRUG

Aspirin \[3 \~5mg/(kg·d) once daily\] or Clopidogrel \[1.0 mg/kg; once daily\]

Warfarin

Intervention Type: DRUG

Warfarin 0.05\~0.12 mg/(kg·d) once daily. INR should maintain within 1.5 to 2.5

Interventions

Rivaroxaban Oral Tablet [Xarelto]

Administered in an age- and bodyweight-adjusted, 15 mg-equivalent dose regimen proposed by model- and clinical evidence-informed precision dosing

Intervention Type: DRUG

Aspirin or Clopidogrel

Aspirin \[3 \~5mg/(kg·d) once daily\] or Clopidogrel \[1.0 mg/kg; once daily\]

Intervention Type: DRUG

Warfarin

Warfarin 0.05\~0.12 mg/(kg·d) once daily. INR should maintain within 1.5 to 2.5

Intervention Type: DRUG

Other Intervention Names

Xarelto; Antiplatelet therapy; Vitamin K Antagonist

Eligibility Criteria

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 3 months;

3. Participant should be able to tolerate oral feeding, nasogastric or gastric feeding;

4. Children aged ≥ 2 years

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. Thrombus within giant coronary aneurysm was confirmed by previous imaging examinations, including two-dimensional echocardiography, computed tomography angiography in coronary artery or coronary angiography

4. An eGFR <30mL/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; CYP3A4, cytochrome P450 isoenzyme 3A4

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fang Liu, MD

Role: STUDY_DIRECTOR

Children's Hospital of Fudan University

Locations

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Fang Liu, MD

Role: CONTACT

liufang@fudan.edu.cn

18017590880

Guangan Dai

Role: CONTACT

gadai24@m.fudan.edu.cn

13580762996

Facility Contacts

Fang Liu, MD.

Role: primary

Other Identifiers

2022-399

Identifier Type: -

Identifier Source: org_study_id