Statins Study in Kawasaki Disease Children With Coronary Artery Abnormalities

Completed

• Conditions: Coronary Artery Abnormalities; Kawasaki Disease

• Registration Number: NCT03915795
• Lead Sponsor: Children's Hospital of Fudan University

Brief Summary

The aim of this study is to investigate the effects of statins on chronic inflammation, coronary artery abnormalities and clinical cardiac events in long-term KD children complicated with severe coronary artery abnormalities, and the feasibility and safety of statins in treatment of KD children.

Detailed Description

Kawasaki disease (KD) is an acute self-limited vasculitis and occurs almost exclusively in childhood. It predominantly affects medium-sized arteries, most commonly the coronary arteries. Although the use of intravenous immunoglobulin (IVIG) has obviously decreased the incidence of coronary arteries (CA) abnormalities, still a part of KD children occur CA abnormalities, even medium, large or giant aneurysms. The coronary aneurysms can develop to thrombus and arterial stenosis, which may cause severe cardiac events, for example, myocardial infarction. It is the main cause of disability and death in KD children. Now KD has been the leading cause of acquired heart disease in children.

Some studies found that ongoing vascular chronic inflammation and oxidative stress persisted in the long-term KD vasculopathy. Endothelial dysfunction, increased stiffness, and intima-media thickening have been noted in both affected coronary arteries and systemic arteries. Statins (hydroxymethylglutaryl coenzyme-A reductase inhibitors) not only are a kind of drug lowering low-density lipoprotein cholesterol, but also have been reported to have potentially beneficial pleiotropic effects on inflammation, endothelial function, oxidative stress, platelet aggregation, coagulation, and fibrinolysis. They have been the cornerstone of therapy for the primary and secondary prevention of atherosclerotic cardiovascular events in adults. In recently years, statins have been considered to be used in KD children with coronary aneurysms. Several short-term small studies in such patients treated with statins have shown reductions in high-sensitivity CRP, improved endothelial function and statins' safety in children. The American Heart Association (AHA) scientific statement on KD published in 2017 suggests that empirical treatment with low-dose statin may be considered for KD patients with past or current aneurysms, regardless of age or sex.

However, the current clinical data about the use of statins in KD children is still very rare. The published researches mainly focused on the endothelial function of peripheral arteries but the effects of statins on CAs and cardiac events have not been included. Therefore, more studies are needed to conform statins' feasibility and safety in children and its clinical application value.

In this study, we will recruit KD children complicated with severe CA abnormalities. These children will be given statins for one year besides other routine treatments. The coronary assessments, clinical and laboratory indexes will be followed up to study the effects of statins on long-term chronic inflammation, CA abnormalities and clinical cardiac events. At the same time, the clinical and laboratory indexes correlated to the side-effects will be monitored regularly to investigate the feasibility and safety of statins in KD children.

Study Timeline

• Study First Submitted: 2019-04-03
• Study First Submitted QC: 2019-04-14
• Study First Posted: 2019-04-16
• Study Start: 2019-08-20
• Primary Completion: 2023-01-31
• Study Completion: 2023-12-30
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-06
• Last Update Posted: 2024-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• >3 months after the onset of KD currently complicated with severe coronary artery abnormalities (medium coronary aneurysms or more severe) The follow-up can be achievable All included children's guardian are required to sign the informed consent form

Exclusion Criteria

• The KD children currently complicated with mild coronary artery abnormalities (small aneurysms or only dilation) The children's age <2 ys The children's guardian don't agree to sign the informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change of coronary artery abnormalities measured by echocardiography	At baseline and one year after taking statin	Internal lumen diameters(mm) and Z score of coronary artery abnormalities measured by echocardiography

Secondary Outcome Measures

Name	Time	Method
Change of high-sensitivity C reactive protein (hsCRP)	At baseline and one year after taking statin	Decrease in hsCRP (mg/L) as a chronic inflammation marker
Incidence of new-onset cardiovascular events	One year after taking statin	Incidence of new-onset cardiovascular events including chest tightness, chest pain, angina, myocardial infarction and so on
Change of LDL-C	At baseline and one year after taking statin	Decrease in LDL-C(mmol/L)
Incidence of side-effects of statin in KD children	At baseline, 3, 6, 9 months and one year after taking statins	Incidences of side-effects including abnormal laboratory indexes (elevated muscle enzyme and liver enzyme), adverse clinical events and growth impacts (weight, height and BMI)
Assessment of myocardial ischemia	At baseline and one year after taking statin	New onset or improved manifestation of myocardial ischemia, assessed by EKG/stress EKG, radionuclide myocardial imaging and/or magnetic resonance imaging

Trial Locations

Locations (1)

Children's Hospital of Fudan University; 🇨🇳 Shanghai, Shanghai, China