Trial of Atorvastatin on the Persistent Coronary Aneurysm in Children With Kawasaki Disease

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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