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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Taiwan University Hospital
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT02114099
First received: June 28, 2010
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Kawasaki Disease
Aneurysm, Coronary
Drug: Atorvastatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • size of coronary aneurysm [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • muscle enzyme and liver function [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: June 2007
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin
prescribe Atorvastatin to see its effect
Drug: Atorvastatin
10 mg qd x1 year
Other Name: Lipitor

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.

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02114099

Contacts
Contact: Ming-Tai Lin, MD 886-2-23123456 ext 71734 mingtailin@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Ming-Tai Lin, MD    886-2-23123456 ext 71734    mingtailin@ntu.edu.tw   
Principal Investigator: Ming-Tai Lin, MD         
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
Principal Investigator: Ming-Tai Lin, MD National Taiwan University Hospital, Taiwan
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT02114099     History of Changes
Other Study ID Numbers: 200612128M
Study First Received: June 28, 2010
Last Updated: April 14, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Kawasaki Disease
Aneurysm, Coronary

Additional relevant MeSH terms:
Mucocutaneous Lymph Node Syndrome
Aneurysm
Coronary Aneurysm
Vascular Diseases
Cardiovascular Diseases
Vasculitis
Lymphatic Diseases
Skin Diseases, Vascular
Skin Diseases
Coronary Disease
Myocardial Ischemia
Heart Diseases
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014