Model-informed Dose Optimization for Rivaroxaban in Children With Giant Coronary Artery Aneurysm After Kawasaki Disease

NCT06978439 | Recruiting Phase 4 DMC

• 1 other identifier: RIVA-KD-pilot
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kawasaki Disease; Pilot Study; Coronary Artery Aneurysm; Rivaroxaban

Keywords

kawasaki disease; giant coronary artery aneurysm; rivaroxaban; model-informed dose optimization; anticoagulant

Outcome Measures

Primary Outcomes (2)

• Occurrence of new thrombosis in coronary arteries

  It is a binary variable. Every echocardiography conducted during study period will be assessed and documented. Investigators will evaluate whether new thrombosis occurs in coronary arteries.

  From enrollment to the 6th month after treatment

• 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

  From enrollment to the 6th month after treatment

Secondary Outcomes (3)

• Occurrence of major adverse cardiovascular event

  From enrollment to the 6th month after treatment

• Any adverse events

  From enrollment to the 6th month after treatment

• Any dose adjustments for rivaroxaban

  From enrollment to the 6th month after treatment

Other Outcomes (2)

• Plasma concentration of rivaroxaban at specific timepoint

  From enrollment to the 6th month after treatment

• Rivaroxaban-calibrated anti-factor Xa activity at specific timepoint

  From enrollment to the 6th month after treatment

Study Arms (1)

Rivaroxaban

EXPERIMENTAL

Rivaroxaban as anticoagulant will be administered for children with giant coronary artery aneurysm after Kawasaki disease. The initial dosing regimen of rivaroxaban is a 15 mg-equivalent, age and bodyweight-adjusted dosing regimen, which was proposed by the model-informed dose optimization study.

Drug: Rivaroxaban (Xarelto)

Interventions

Rivaroxaban (Xarelto) DRUG

Administered in an age- and bodyweight-adjusted, 15 mg-equivalent dose regimen proposed by model-informed dose optimization study

Also known as: Anticoagulation

Rivaroxaban

Eligibility Criteria

• Age: 1 Month - 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 6 months;
• Participant should be able to tolerate oral feeding, nasogastric or gastric feeding;
• Children aged 1 Month to\<18 years, bodyweight ≥ 2600g.

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.
• Hypersensitivity or any other contraindications listed in the local labeling for the comparator treatment or experimental treatment
• An eGFR \<30 mL/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 (TB); 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

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

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, MD

CONTACT

13580762996; gadai24@m.fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2025
• First Posted: May 18, 2025
• Study Start: January 10, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)