A Trial to Evaluate the Efficacy of Immunoglobulin Plus Steroid for Prevention of Coronary Artery Abnormalities in Taiwanese Refractory Kawasaki Disease (RAST Study) (RAST)

A Randomized Open-label Trial to Evaluate the Efficacy of Immunoglobulin Plus Steroid for Prevention of Coronary Artery Abnormalities in Taiwanese Refractory Kawasaki Disease (RAST Study)

Background:

Kawasaki disease (KD), most popular acquired heart disease in childhood, is characterized by diffuse vasculitis, especially on the middle-sized muscular arteries. IVIG and aspirin are currently standard treatment. However, 10-15% of KD patients have poor response to such treatment and suffer from higher risk of coronary involvement. Recently, combination of prednisolone and IVIG has been shown effective to lower the chance of refractory to IVIG treatment and subsequent coronary lesions. However, no randomized trial on the steroid efficacy was ever conducted in Taiwan.

Aim:

Prospectively randomized open-label trial to evaluate the add-on effect of prednisolone in the refractory KD children.

Methods:

For the KD patients with fever persisted or relapsed 24 hours after the ending of IVIG infusion, they will be randomized into two group: IVIG group (I) and IVIG + prednisolone group (P). The KD patients in the P group will have in addition to IVIG, oral prednisolone 2mg/kg/day for at least 5 days. The difference in the response rate and percentage of coronary involvement will be compared between I and P groups.

Predicted results:

We plan to enroll 100 refractory KD patients, 50 patients for each group. We predict the risk of coronary involvement can be reduced from 30% to 15%.

Study Overview

• Status: Unknown
• Conditions: Kawasaki Disease; Steroid; Immuoglobulin
• Intervention / Treatment: Drug: Prednisolone; Biological: immunoglobulin

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ming-Tai Lin, MD, PhD; Phone Number: 71734 886-2-23123456; Email: mingtailin@ntu.edu.tw

Study Locations

• Taiwan
  • Taichung, Taiwan, 400
    • Recruiting
    • China Medical University Hospital
    • Contact: Jeng-Sheng Chang, MD; Phone Number: 4646 886-4-22052121; Email: d0669@mail.cmuh.org.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• KD (Kawasaki disease) patients who failed to respond to the initial IVIG as those who had persistent fever that lasted for more than 24 hours (nonresponse to the initial IVIG) or recrudescent fever associated with KD symptoms after an afebrile period (relapse).

Exclusion Criteria:

• KD patients, those diagnosed on or after day 9 of illness (the first illness day was defined as the day of fever onset), those with coronary artery abnormalities before enrolment, those who were afebrile before enrolment, those who had received steroids (oral, intravenous, intramuscular, or subcutaneous) in the 30 days before the study or intravenous immunoglobulin in the previous 180 days, those with concomitant severe medical disorders (eg, immunodeficiency, chromosomal anomalies, congenital heart diseases, metabolic diseases, nephritis, collagen diseases), and those with suspected infectious disease, including sepsis, septic meningitis, peritonitis, bacterial pneumonia, varicella, and influenza.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: S group; IVIG (2g/Kg in 12 hours)+oral prednisolone (2mg/Kg/day for 5 days)	Drug: Prednisolone; Prednisolone 2mg/Kg/day for 5 days; Biological: immunoglobulin; immunoglobulin 2g/Kg for 12 hours
Placebo Comparator: I group; IVIG (2g/Kg in 12 hours)	Biological: immunoglobulin; immunoglobulin 2g/Kg for 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximal coronary z score	echocardiography	one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fever more than 38 degree	from end of second course of IVIG	3 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Ming-Tai Lin, MD, PhD, National Taiwan University Hospital, Taipei, Taiwan; Study Director: Mei-Hwan Wu, MD, PhD, National Taiwan University Hospital, Taipei, Taiwan

Publications and helpful links

General Publications

• Kobayashi T, Kobayashi T, Morikawa A, Ikeda K, Seki M, Shimoyama S, Ishii Y, Suzuki T, Nakajima K, Sakamoto N, Arakawa H. Efficacy of intravenous immunoglobulin combined with prednisolone following resistance to initial intravenous immunoglobulin treatment of acute Kawasaki disease. J Pediatr. 2013 Aug;163(2):521-6. doi: 10.1016/j.jpeds.2013.01.022. Epub 2013 Feb 26.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2013
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: June 25, 2017
• First Submitted That Met QC Criteria: June 26, 2017
• First Posted (Actual): June 27, 2017

Study Record Updates

• Last Update Posted (Actual): June 27, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Lymphatic Diseases; Vasculitis; Skin Diseases, Vascular; Mucocutaneous Lymph Node Syndrome; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: 201308036MIND

Plan for Individual participant data (IPD)

Study Data/Documents

1. Clinical trial approval
   Information identifier: 201308036MIND

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No