Methylprednisolone Pulse Therapy for Coronary Artery Dilatation or Aneurysm Formation in Kawasaki Disease

Study Overview
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Brief Summary
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In this study, the investigator plan to prescribe Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery lesions or aneurysm formation beyond acute stage to investigate the role for vasculitis of KD or regression of dilatation.

Detailed Description
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Kawasaki disease is the most common systemic vasculitis in children. Coronary artery aneurysms may develop in 20-25% of untreated patients. Intravenous immune globulin (IVIG) can reduce coronary-artery aneurysms to 3-5%. Numerous studies and clinical trials had pointed out that corticosteroid treatment (pulse therapy or not) could lower the incidence of coronary artery abnormality in high-risk KD patients. However, the therapeutic effect of corticosteroid in KD patients with aneurysm formation after acute stage was never mentioned. There is no effective treatment for aneurysm formation available in KD after acute stage. Methylprednisolone pulse therapy (MP pulse) was used for treatment of KD during acute stage since more than 20 years ago. MP pulse plus IVIG seems not benefit for KD patients but benefit for IVIG resistant KD patients or for high-risk group of CAL formation/ IVIG resistance group. MP pulse therapy is well document used in autoimmune disease vasculitis such as SLE, rheumatoid arthritis, dermatomyosis...etc. Taking together, MP pulse is effective and safe for KD patients during acute stage. In this study, the investigators plan to use MP pulse in KD patients with CAL or aneurysm formation beyond acute stage to investigate the role of vasculitis of KD or regression of dilatation. Methods: The investigators conducted a prospective study of methylprednisolone pulse therapy (MP pulse) for KD patients with coronary aneurysm or dilatation formation. The investigators will enroll these patients to receive methylprednisolone pulse (MP pulse, 30mg/kg, Max:1g/day for continue 3 days) for treatment. Together with other anti-inflammatory oral medicine including monteleukast, Dextromethorphan(DXM), prednisolone, and ketotifen as supplementary treatment. The specific aim of this study is the regression of coronary artery aneurysm after MP pulse therapy. Under the hypothesis and specific aim, the investigators plan to do in the following 3 years: During the 1st year, the investigators will enroll for 5-10 cases for safety surveys including blood pressure monitoring, inflammatory markers, liver function, renal function, electrolyte imbalance, growth problems as Phase I study. In the 2nd and 3rd year of this study, the investigators will enroll for 20-30 cases for an effective survey as Phase II study. Results from this study will help clinicians to treat aneurysm formation or coronary artery dilatation in KD patients and reduce the activity limitation of patients, reduce the medical resource in those patients. The investigators may provide the first treatment for aneurysm in KD.

Official Title
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Methylprednisolone Pulse Therapy for Coronary Artery Dilatation or Aneurysm Formation in Kawasaki Disease

Conditions
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Mucocutaneous Lymph Node Syndrome

Intervention / Treatment
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* Drug: Methylprednisolone Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kawasaki disease patients with coronary artery dilation or aneurysm formation after acute stage (at lease 3 weeks after IVIG treatment) Exclusion Criteria: patients meet the contraindications of Methylprednisolone sodium succinate, e.g., allergic to Methylprednisolone sodium succinate, premature infant, immune system related thrombocytopathy, immunodeficiency, any congenital diseases.

Ages Eligible for Study
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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
Interventional Model Description: single arm, phase 1 study of methylprednisolone pulse therapy safety in treatment of aneurysm or coronary artery dilation of Kawasaki disease.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants treated with MP pulse<br>Selected participants will be given MP pulse treatment | Drug: Methylprednisolone Injection<br>* methylprednisolone pulse therapy, 30mg/kg, with maximal dose of 1000mg/day, for continue 3 days.<br>* Other names: methylprednisolone pulse therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body weight in Kilogram | 4 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body weight in Kilogram | 8 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body weight in Kilogram | 12 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body weight in Kilogram | 16 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body weight in Kilogram | 20 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body weight in Kilogram | 24 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body height in centimeter | 4 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body height in centimeter | 8 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body height in centimeter | 12 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body height in centimeter | 16 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body height in centimeter | 20 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of body height in centimeter | 24 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of blood pressure & intraocular pressure in mmHg | 4 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of blood pressure & intraocular pressure in mmHg | 8 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of blood pressure & intraocular pressure in mmHg | 12 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of blood pressure & intraocular pressure in mmHg | 16 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of blood pressure & intraocular pressure in mmHg | 20 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of blood pressure & intraocular pressure in mmHg | 24 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Sodium, Potassium, Chlorine level in blood in MEQ/L | 4 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Sodium, Potassium, Chlorine level in blood in MEQ/L | 8 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Sodium, Potassium, Chlorine level in blood in MEQ/L | 12 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Sodium, Potassium, Chlorine level in blood in MEQ/L | 16 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Sodium, Potassium, Chlorine level in blood in MEQ/L | 20 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Sodium, Potassium, Chlorine level in blood in MEQ/L | 24 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Calcium & Fibrinogen level in blood in mg/dl | 4 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Calcium & Fibrinogen level in blood in mg/dl | 8 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Calcium & Fibrinogen level in blood in mg/dl | 12 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Calcium & Fibrinogen level in blood in mg/dl | 16 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Calcium & Fibrinogen level in blood in mg/dl | 20 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of Calcium & Fibrinogen level in blood in mg/dl | 24 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of prothrombin time & activated partial thromboplastin time in second | 4 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of prothrombin time & activated partial thromboplastin time in second | 8 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of prothrombin time & activated partial thromboplastin time in second | 12 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of prothrombin time & activated partial thromboplastin time in second | 16 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of prothrombin time & activated partial thromboplastin time in second | 20 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of prothrombin time & activated partial thromboplastin time in second | 24 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of protein C & protein S level in ％ | 4 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of protein C & protein S level in ％ | 8 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of protein C & protein S level in ％ | 12 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of protein C & protein S level in ％ | 16 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of protein C & protein S level in ％ | 20 weeks from enrollment | 
| Incidence of Treatment-Emergent Adverse Events and physical effects of Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery aneurysms | Measurement of protein C & protein S level in ％ | 24 weeks from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiography on the coronary artery lesion of Kawasaki disease | Use echocardiography to measure the diameter of coronary artery (including right coronary artery [RCA], left coronary artery [LCA] and left anterior descending [LAD]) to investigate the regression of coronary artery dilatation or aneurysm formation. The dilatation is define the diameter of coronary artery. For children under 5 yrs, the diameter should not be wider than 3mm. For children over 5 yrs, the diameter should not be wider than 4mm. Adjacent segment artery should not be wider than 1.5 times. | 4 weeks from enrollment | 
| Echocardiography on the coronary artery lesion of Kawasaki disease | Use echocardiography to measure the diameter of coronary artery (including right coronary artery [RCA], left coronary artery [LCA] and left anterior descending [LAD]) to investigate the regression of coronary artery dilatation or aneurysm formation. The dilatation is define the diameter of coronary artery. For children under 5 yrs, the diameter should not be wider than 3mm. For children over 5 yrs, the diameter should not be wider than 4mm. Adjacent segment artery should not be wider than 1.5 times. | 8 weeks from enrollment | 
| Echocardiography on the coronary artery lesion of Kawasaki disease | Use echocardiography to measure the diameter of coronary artery (including right coronary artery [RCA], left coronary artery [LCA] and left anterior descending [LAD]) to investigate the regression of coronary artery dilatation or aneurysm formation. The dilatation is define the diameter of coronary artery. For children under 5 yrs, the diameter should not be wider than 3mm. For children over 5 yrs, the diameter should not be wider than 4mm. Adjacent segment artery should not be wider than 1.5 times. | 12 weeks from enrollment | 
| Echocardiography on the coronary artery lesion of Kawasaki disease | Use echocardiography to measure the diameter of coronary artery (including right coronary artery [RCA], left coronary artery [LCA] and left anterior descending [LAD]) to investigate the regression of coronary artery dilatation or aneurysm formation. The dilatation is define the diameter of coronary artery. For children under 5 yrs, the diameter should not be wider than 3mm. For children over 5 yrs, the diameter should not be wider than 4mm. Adjacent segment artery should not be wider than 1.5 times. | 16 weeks from enrollment | 
| Echocardiography on the coronary artery lesion of Kawasaki disease | Use echocardiography to measure the diameter of coronary artery (including right coronary artery [RCA], left coronary artery [LCA] and left anterior descending [LAD]) to investigate the regression of coronary artery dilatation or aneurysm formation. The dilatation is define the diameter of coronary artery. For children under 5 yrs, the diameter should not be wider than 3mm. For children over 5 yrs, the diameter should not be wider than 4mm. Adjacent segment artery should not be wider than 1.5 times. | 20 weeks from enrollment | 
| Echocardiography on the coronary artery lesion of Kawasaki disease | Use echocardiography to measure the diameter of coronary artery (including right coronary artery [RCA], left coronary artery [LCA] and left anterior descending [LAD]) to investigate the regression of coronary artery dilatation or aneurysm formation. The dilatation is define the diameter of coronary artery. For children under 5 yrs, the diameter should not be wider than 3mm. For children over 5 yrs, the diameter should not be wider than 4mm. Adjacent segment artery should not be wider than 1.5 times. | 24 weeks from enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kawasaki Disease, aneurysm formation, coronary artery dilatation, Methylprednisolone, Pulse therapy