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

NCT05643651 | Recruiting Phase 4 DMC

• 1 other identifier: 2022-399
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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

Conditions

Kawasaki Disease; Coronary Artery Aneurysm

Keywords

Kawasaki disease; Giant coronary artery aneurysm; Rivaroxaban; Warfarin; Anticoagulation

Outcome Measures

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).

  From Day 1 of treatment to the third month after treatment initiation

Secondary Outcomes (15)

• Occurrence of new thrombosis in coronary arteries

  From Day 1 of treatment to the third month after treatment initiation

• Time to first new thrombosis in coronary arteries

  From Day 1 of treatment to the third month after treatment initiation

• Composite of Major bleeding or Clinically relevant non-major bleeding event

  From Day 1 of treatment to the third month after treatment initiation

• Occurrence of major bleeding

  From Day 1 of treatment to the third month after treatment initiation

• Occurrence of clinically relevant non-major bleeding (CRNM)

  From Day 1 of treatment to the third month after treatment initiation

Other Outcomes (1)

• Genetic polymorphism

  From Day 1 of treatment to the third month after treatment initiation

Study Arms (2)

Rivaroxaban+Antiplatelet drug

EXPERIMENTAL

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.

Drug: Rivaroxaban Oral Tablet [Xarelto]; Drug: Aspirin or Clopidogrel

Standard antithrombotic care

ACTIVE COMPARATOR

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.

Drug: Aspirin or Clopidogrel; Drug: Warfarin

Interventions

Rivaroxaban Oral Tablet [Xarelto] DRUG

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

Also known as: Xarelto

Rivaroxaban+Antiplatelet drug

Aspirin or Clopidogrel DRUG

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

Also known as: Antiplatelet therapy

Rivaroxaban+Antiplatelet drug; Standard antithrombotic care

Warfarin DRUG

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

Also known as: Vitamin K Antagonist

Standard antithrombotic care

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)
• Platelet count \< 100 x 109/L
• 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
• Sustained uncontrolled hypertension defined as systolic and/or diastolic blood pressure \>95 th age percentile
• 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)
• Concomitant use of strong inducers of CYP3A4, including but not limited to rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
• Hypersensitivity or any other contraindications listed in the local labeling for the comparator treatment or experimental treatment
• Inability to cooperate with the study procedures and follow-up visits
• Refuse to provide informed consent eGFR, estimated glomerular filtration rate; ULN, upper level of normal; TB, total bilirubin; CYP3A4, cytochrome P450 isoenzyme 3A4

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead

Study Sites (1)

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

RECRUITING

MeSH Terms

Conditions

Mucocutaneous Lymph Node Syndrome; Coronary Aneurysm

Interventions

Rivaroxaban; Aspirin; Clopidogrel; Warfarin; acarboxyprothrombin

Condition Hierarchy (Ancestors)

Vasculitis; Vascular Diseases; Cardiovascular Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Aneurysm

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Study Officials

• Fang Liu, MD

  Children's Hospital of Fudan University

  STUDY DIRECTOR

Central Study Contacts

Fang Liu, MD

CONTACT

18017590880; liufang@fudan.edu.cn

Guangan Dai

CONTACT

13580762996; gadai24@m.fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Investigator, Participant and Care provider will not be masked. However, sonographer who is responsible for assessing coronary artery lesions should be masked.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2022
• First Posted: December 9, 2022
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)