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

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.

Study Overview

• Status: Recruiting
• Conditions: Mucocutaneous Lymph Node Syndrome
• Intervention / Treatment: Drug: Methylprednisolone Injection

Detailed Description

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:

1. 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.
2. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ho-Chang Kuo, MD; PhD; Phone Number: 8320 +886-7-7317123; Email: erickuo48@yahoo.com.tw

Study Locations

• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Participants treated with MP pulse; Selected participants will be given MP pulse treatment	Drug: Methylprednisolone Injection; methylprednisolone pulse therapy, 30mg/kg, with maximal dose of 1000mg/day, for continue 3 days.; Other Names: methylprednisolone pulse therapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 15, 2020
• Primary Completion (ANTICIPATED): April 15, 2021
• Study Completion (ANTICIPATED): August 31, 2023

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (ACTUAL): August 11, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Methylprednisolone; Kawasaki Disease; aneurysm formation; coronary artery dilatation; Pulse therapy
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Lymphatic Diseases; Pathological Conditions, Anatomical; Vasculitis; Skin Diseases, Vascular; Coronary Disease; Aneurysm; Dilatation, Pathologic; Mucocutaneous Lymph Node Syndrome; Coronary Aneurysm; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: MP pulse in KD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes