Kawasaki DiseasePhase 4NCT06978439
Model-informed Dose Optimization for Rivaroxaban in Children With Giant Coronary Artery Aneurysm After Kawasaki Disease
A Phase 4 study testing Rivaroxaban (Xarelto) in people with Kawasaki Disease and Pilot Study, run by Children's Hospital of Fudan University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month to 18 years
- Conditions the study is for
- Kawasaki Disease, Pilot Study, Coronary Artery Aneurysm
- What is being tested?
- Rivaroxaban (Xarelto)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 10 Jan 2024to 31 Dec 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Children's Hospital of Fudan University
Shanghai, Shanghai Municipality, 201102
Fang Liu, MD., 18017590880, liufang@fudan.edu.cn
Fang Liu, MD
About this study
Official title: Rivaroxaban in Chinese Children With Giant Coronary Artery Aneurysm After Kawasaki Disease: a Pilot Study
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.
Read the detailed description
Giant coronary artery aneurysm (GCAA) is a rare but severe cardiac complication of Kawasaki disease (KD). Due to the abnormal blood rheology and the hyper-inflammatory response accompanied by thrombocytosis during the acute phase, patients with GCAA are at high risk of coronary artery thrombosis and major adverse cardiovascular events.In such instances, lifelong antiplatelet (aspirin or clopidogrel) and anticoagulant therapy (warfarin or low molecular weight heparin, LMWH) may become necessary.
In 2022, two compounds, the direct activated Factor X (FXa) inhibitor rivaroxaban was approved by international regulatory agencies for two specific pediatric indications, supported by pharmacometrics models. For instance, a dosing regimen matching exposures of 20 mg daily in adults (the 20 mg-equivalent dosing regimen) is indicated for children under 18 years with venous thromboembolism (VTE). Secondly, a dosing regimen matching exposures of 10 mg daily in adults (the 10 mg-equivalent dosing regimen) is indicated for post-Fontan patients aged two years or older, as shown in the UNIVERSE study, which compared rivaroxaban to aspirin. However, no trials have yet compared rivaroxaban with warfarin/LMWH in pediatric patients with GCAA after KD.
Inter-ethnic population pharmacokinetic (PPK) analyses have suggested that Asian patients may require a lower dosage of rivaroxaban, consistent with the findings from the J-ROCKET trail in Japanese adults. Accordingly, the maximum dosage for Japanese children with VTE (≥ 50 kg) has reduced from 20 mg q24h (every 24 hours) to 15 mg q24h. However, reports on rivaroxaban use in pediatric patients with GCAA after KD, especially in those from Asian countries, remains limited. Its application is more challenging due to (i) increased bleeding risk from concomitant antiplatelet drug use; (ii) the predominance of younger patients (typically < 3 years) with variability in hepatic and renal function, as well as growth and development.3 Given the low incidence of GCAA, quantitative pharmacometrics is a highly promising approach for precision dosing of rivaroxaban in these patients.
Therefore, the investigators retrospectively collected the clinical experience of rivaroxaban off-label use in Chinese pediatric patients with GCAA after KD from 2023.1 to 2023.12. With clinical evidence and model-extrapolation, the investigators conducted a quantitative pharmacometrics model-based dose optimization study and proposed a 15 mg-equivalent dosing regimen for thromboprophylaxis in Chinese children with GCAA after KD, those who require dual antithrombotic therapy.
This pilot study aims to assess the potential of rivaroxaban for thromboprophylaxis in pediatric patients with KD after GCAA. Specifically, this study seeks to: (ⅰ) preliminarily evaluate the feasibility, efficacy and safety of the 15 mg-equivalent dosing regimen in target population, (ii) provide pharmacokinetic (PK)/pharmacodynamic (PD) data on rivaroxaban in Chinese children.
- Conditions
- Kawasaki Disease, Pilot Study, Coronary Artery Aneurysm, Rivaroxaban
- Being tested
- Rivaroxaban (Xarelto)
- Keywords
- kawasaki disease, giant coronary artery aneurysm, rivaroxaban, model-informed dose optimization, anticoagulant
- Medical subject headings
- Mucocutaneous Lymph Node Syndrome, Coronary Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rivaroxaban (Xarelto)Drug
Also called Anticoagulation
Administered in an age- and bodyweight-adjusted, 15 mg-equivalent dose regimen proposed by model-informed dose optimization study
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Rivaroxaban (Xarelto) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: From enrollment to the 6th month after treatment
Secondary outcomes (3)
Occurrence of major adverse cardiovascular event
It is a binary variable. Major adverse cardiovascular event (MACE) includes unstable angina, acute myocardial infarction, stroke, hospitalization for heart failure, unplanned revascularization, cardiovascular death. If any of the MACEs occur during the study period, it will be recorded as 1; otherwise, it will be recorded as 0. The definition of each MACE refers to the following guidelines and consensus: 2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials, 2019 European Society of Cardiology Guidelines for the diagnosis and management of chronic coronary syndromes, Fourth universal definition of myocardial infarction, and 2023 European Society of Cardiology Guidelines for the management of acute coronary syndromes.
Measured: From enrollment to the 6th month after treatment
Any adverse events
It is a text variable. If any adverse events( including durg allergy, severe infection, hepatic dysfunction, renal dysfunction, hypertension, fatigue, abdominal pain or others) occur will be reported to the data and safety monitoring board. The detail of adverse event will be recorded, including classification of adverse event, time of occurrence, symptoms, treatment, resolution time, and outcome.
Measured: From enrollment to the 6th month after treatment
Any dose adjustments for rivaroxaban
It is a text variable. Any dose adjustments for rivaroxaban will be recorded, including time of dose adjustment, reason for dose adjustment, dosage, and outcome. Rivaroxaban plasma concentration and rivaroxaban-calibrated anti-factor Xa activity will be measured after at least 3 consecutive doses
Measured: From enrollment to the 6th month after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2025
- Study start10 Jan 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kawasaki DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fang Liu, MD, Study director, Children's Hospital of Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06978439
- Sponsor's protocol ID
- RIVA-KD-pilot
- Status last verified
- Oct 2026
- First submitted
- 11 May 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No