Statins Study in Kawasaki Disease Children With Coronary Artery Abnormalities

Application of Statins in Long-term Treatments of Kawasaki Disease Complicated With Severe Coronary Artery Abnormalities in Children

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.

Study Overview

• Status: Completed
• Conditions: Kawasaki Disease; Coronary Artery Abnormalities

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 Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Children's Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The KD children admitted to the Cardiology ward in Children's Hospital of Fudan University, Shanghai, China

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Investigators: Study Director: Fang Liu, MD, Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2019
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 14, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: statins; Kawasaki Disease; coronary artery abnormalities
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Lymphatic Diseases; Vasculitis; Skin Diseases, Vascular; Congenital Abnormalities; Mucocutaneous Lymph Node Syndrome
• Other Study ID Numbers: Statins study in KD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No