Brief Title
Trial of Atorvastatin on the Persistent Coronary Aneurysm in Children With Kawasaki Disease
Official Title
An Open Label, Non-comparative Phase II Trial to Evaluate the Effects of Atorvastatin on the Persistent Coronary Arterial Aneurysm in Children With Kawasaki Disease: Safety and Efficacy
Brief Summary
Background Kawasaki disease (KD) is characterized by fever, bilateral nonexudative
conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and
cervical lymphadenopathy. Incidence of late coronary artery aneurysms or ectasia, which may
lead to myocardial infarction (MI), sudden death, or ischemic heart disease, decreased after
the introduction of intravenous immunoglobulin therapy. However, significant persistent
coronary arterial lesions or aneurysms may still occur in about 1-3 % of the patients.
Atorvastatin (Lipitor®), a kind of statin, is a selective competitive inhibitor of
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This drug had been safely and
widely used for treatment of adult hyperlipidemia, prevention of coronary heart disease and
familial hypercholesterolemia in childhood. In addition to the cholesterol-lowering effects,
statins exerts diverse cellular, cholesterol-independent effects, including improvement in
endothelial function, inhibition of neurohormonal activation, and reduction in levels of
proinflammatory cytokines. Based on the above concepts, some patients with infrarenal
abdominal aortic aneurysms received statin therapies and then the growth rate of aneurysms
slowed down.
Therefore, the investigators may hypothesize that Atorvastatin is helpful in the regression
of persistent coronary lesions in KD patients due to its effect of anti-inflammation. In
NTUH, there are about 20 KD patients with coronary lesions persistent for many years. And the
investigators plan to conduct the clinical trial with atorvastatin to evaluate the effects of
Atorvastatin on the persistent coronary arterial lesions/aneurysms in children with Kawasaki
disease including safety and efficacy.
Methods
There are around 20 KD patients eligible for this study. After they sign the IRB-approved
ICF, they will be enrolled for this study. Briefly, this study is divided into three stages:
screening & enrollment stage (I), treatment & follow-up stage (II) for 1 year and final data
analysis stage (III). Measurements include basic vital sign, electrocardiography, liver
function, muscle enzyme, inflammatory markers and echocardiography.
Predicted results
1.Oral atorvastatin therapy can effectively prevent the progression of coronary lesions in KD
patients.
Detailed Description
Background Kawasaki disease (KD) is characterized by fever, bilateral nonexudative
conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and
cervical lymphadenopathy. Incidence of late coronary artery aneurysms or ectasia, which may
lead to myocardial infarction (MI), sudden death, or ischemic heart disease, decreased after
the introduction of intravenous immunoglobulin therapy. However, significant persistent
coronary arterial lesions or aneurysms may still occur in about 1-3 % of the patients.
Aspirin and warfarin, the recommended medication to prevent and decrease the incidence of
coronary artery events, can't guarantee the coronary patency in these KD patients. Thus, it's
urgent to look for an effective and safe treatment to make sure the coronary lesions will
stabilize even regress gradually.
Several groups studied the clinical characteristics of KD patients with coronary sequelae and
showed there was association between elevated inflammatory markers and the persistence of
coronary lesions. Atorvastatin (Lipitor®), a kind of statin, is a selective competitive
inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This drug had been
safely and widely used for treatment of adult hyperlipidemia, prevention of coronary heart
disease and familial hypercholesterolemia in childhood. In addition to the
cholesterol-lowering effects, statins exerts diverse cellular, cholesterol-independent
effects, including improvement in endothelial function, inhibition of neurohormonal
activation, and reduction in levels of proinflammatory cytokines. Based on the above
concepts, some patients with infrarenal abdominal aortic aneurysms received statin therapies
and then the growth rate of aneurysms slowed down.
Therefore, the investigators may hypothesize that Atorvastatin is helpful in the regression
of persistent coronary lesions in KD patients due to its effect of anti-inflammation. In
NTUH, there are about 20 KD patients with coronary lesions persistent for many years. And the
investigators plan to conduct the clinical trial with atorvastatin to evaluate the effects of
Atorvastatin on the persistent coronary arterial lesions/aneurysms in children with Kawasaki
disease including safety and efficacy.
Methods
There are around 20 KD patients eligible for this study. After they sign the IRB-approved
ICF, they will be enrolled for this study. Briefly, this study is divided into three stages:
screening & enrollment stage (I), treatment & follow-up stage (II) for 1 year and final data
analysis stage (III). Measurements include basic vital sign, electrocardiography, liver
function, muscle enzyme, inflammatory markers and echocardiography.
Predicted results
1.Oral atorvastatin therapy can effectively prevent the progression of coronary lesions in KD
patients.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
size of coronary aneurysm
Secondary Outcome
muscle enzyme and liver function
Condition
Kawasaki Disease
Intervention
Atorvastatin
Study Arms / Comparison Groups
Atorvastatin
Description: prescribe Atorvastatin to see its effect
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
June 2007
Completion Date
December 2016
Primary Completion Date
December 2015
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of Kawasaki Disease with giant aneurysm
- Must be older than 10 years old
Exclusion Criteria:
- Subjects ever received coronary artery bypass graft (CABG) surgery.
- Subjects have active hepatitis or persistent abnormal liver function such as elevated
GOT and GPT.
- Subjects have the past history of rhabdomyolysis.
- Female subjects are pregnant or plan for child-bearing during study periods.
Gender
All
Ages
10 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Ming-Tai Lin, MD, 886-2-23123456, [email protected]
Location Countries
Taiwan
Location Countries
Taiwan
Administrative Informations
NCT ID
NCT02114099
Organization ID
200612128M
Responsible Party
Sponsor
Study Sponsor
National Taiwan University Hospital
Collaborators
National Science Council, Taiwan
Study Sponsor
Ming-Tai Lin, MD, Principal Investigator, National Taiwan University Hospital, Taiwan
Verification Date
April 2014