Clinical trial NCT05643651: Rivaroxaban for Children With Giant Coronary Artery Aneurysms After Kawasaki Disease
Official title: Rivaroxaban Versus Warfarin for Thromboprophylaxis in Children With Giant Coronary Artery Aneurysms After Kawasaki Disease: a Multicenter, Open-label, Parallel, Exploratory, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Kawasaki Disease
Coronary Artery Aneurysm
Keywords: Kawasaki disease
Giant coronary artery aneurysm
Rivaroxaban
Warfarin
Anticoagulation
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2022-12-09
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 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.

This study is a multicenter, open-label, exploratory, randomized controlled trial to evaluate the feasibility, safety and effectiveness of rivaroxaban for thromboprophylaxis in Chinese children with giant coronary artery aneurysms after Kawasaki disease, following the 15 mg-equivalent, age-, and bodyweight-adjusted dosing regimen. Participants will be randomly assigned to the control or experimental groups. Randomization ratio will be 1:1. 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 for antithromboprophylaxis between warfarin and rivaroxaban

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 antithromboprophylaxis 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. 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. If taking warfarin before recruitment, INR should reach the target range (1.5-2.5) in three consecutive tests in the past month, and each test at least one week apart.
5. An eGFR \<30mL/min/1.73 m2 (For children younger than 1 year, serum creatinine results above 97.5th percentile)
6. Platelet count \< 100 x 109/L
7. 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
8. Sustained uncontrolled hypertension defined as systolic and/or diastolic blood pressure \>95 th age percentile
9. 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)
10. Concomitant use of strong inducers of CYP3A4, including but not limited to rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
11. Hypersensitivity or any other contraindications listed in the local labeling for the comparator treatment or experimental treatment
12. Inability to cooperate with the study procedures and follow-up visits
13. Refuse to provide informed consent eGFR, estimated glomerular filtration rate; ULN, upper level of normal; TB, total bilirubin (TB); CYP3A4, cytochrome P450 isoenzyme 3A4

Primary outcomes:
measure: The number of coronary arteries with new thrombosis
timeFrame: From enrollment to the 6th month after treatment
Secondary outcomes:
measure: Time to discovering new thrombosis in coronary arteries
timeFrame: From enrollment to the 6th month after treatment
measure: Occurrence of major adverse cardiovascular event
timeFrame: From enrollment to the 6th month after treatment
measure: Time to major adverse cardiovascular event
timeFrame: From enrollment to the 6th monthFrom enrollment to the 6th month after treatment
measure: Composite of Major bleeding or Clinically relevant non-major bleeding event
timeFrame: From enrollment to the 6th month after treatment
measure: Any adverse events
timeFrame: From enrollment to the 6th month after treatment
measure: Discontinuation anticoagulant due to regression of coronary artery lesions
timeFrame: From enrollment to the 6th month after treatment
measure: Changes in Z-score of each coronary artery aneurysms
timeFrame: From enrollment to the 6th month after treatment
Other outcomes:
measure: Plasma concentration of rivaroxaban at specific timepoint
timeFrame: From enrollment to the 6th month after treatment
measure: Anti-factor Xa activity at specific timepoint
timeFrame: From enrollment to the 6th month after treatment
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Fang Liu, MD
role: STUDY_DIRECTOR
References: