Pharmacokinetics (PK)/Safety Study of Atorvastatin in Children With Kawasaki Disease and Coronary Artery Abnormalities

Study Overview
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Brief Summary
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Kawasaki disease (KD) is the leading cause of acquired heart disease in children in the developed world. Despite available treatment, 25% of children in San Diego County appropriately treated for KD develop coronary artery abnormalities that could lead to complications later in life, including heart attack. Although investigators can identify children with KD that have these coronary artery abnormalities, there is no approved additional treatment to decrease coronary artery inflammation and arrest or prevent damage to the coronary arteries. Inflammation and damage to the arterial wall is central to these coronary artery abnormalities. Statins, a class of drugs that is known for lowering cholesterol, have also been shown to decrease inflammation in general as well as at the level of the vessel wall. Therefore, the investigators propose to study the safety of the drug atorvastatin in children with coronary artery abnormalities from KD.

Official Title
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Phase I/IIa Study of Pharmacokinetics and Safety of Atorvastatin in Children With Coronary Artery Abnormalities Secondary to Kawasaki Disease

Conditions
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Kawasaki Disease

Intervention / Treatment
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* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age ≥ 2 years to 17 years old Meets clinical criteria for KD according to American Heart Association guidelines (Table 2): Fever (T≥38oC or 100.4oC) ≥ 3 days and ≥ 2 clinical criteria with left anterior descending coronary artery/right coronary artery z-score ≥ 2.5 or an aneurysm (≥ 1.5 x the adjacent segment) of one of the coronary arteries Patient presents within the first 20 days after fever onset Parent or legal guardian able and willing to provide informed consent and subject willing and able to provide assent when appropriate. Post-menarchal females: Negative pregnancy test at screening and willing to use two forms of contraception during the study Males engaging in sexual activity that could lead to pregnancy must use a condom. Exclusion Criteria: Use of a statin, fibrate, or niacin within the 3 months prior to enrollment Have any chronic disease, except asthma, atopic dermatitis, autism or controlled seizure disorder Screening creatine phosphokinase (CK) ≥ 3x upper limit of normal for age Patient taking a CYP3A4 inhibitor (ie. cyclosporine or clarithromycin) in the last 7 days Patient has a history of allergy to atorvastatin or its derivatives

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvasatin<br>Atorvastatin dose titration to maximum tolerated dose | Drug: Atorvastatin<br>* Atorvastatin dose titration to maximum tolerated dose (once daily for 6 weeks)<br>* Other names: Lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With SAE | Number of participants who experienced an SAE within the 6 week study period | At 6 weeks after initiation of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kawasaki disease