A Multi-center, Randomized to Compare the Efficacy of IVIG Alone and IVIG Plus High-dose Aspirin in Kawasaki Disease

Not Applicable

• Conditions: Kawasaki Disease
• Interventions: Other: IVIG and Aspirin; Other: IVIG only

• Registration Number: NCT02951234
• Lead Sponsor: Chang Gung Memorial Hospital

Brief Summary

Kawasaki disease (KD) is an acute febrile systemic vasculitis most commonly seen in children under the age of 5 years old. This trial has been designed as a multi-center, prospective, randomized controlled, evaluator-blinded trial with two parallel groups to determine whether IVIG alone as the primary therapy in acute-stage KD is as effective as IVIG combined with high-dose aspirin therapy. The primary endpoint is defined as CAL formation at 6-8 weeks.

Detailed Description

Background: Kawasaki disease (KD) is an acute febrile systemic vasculitis most commonly seen in children under the age of 5 years old. High-dose aspirin is often administered, but the duration of such treatment varies. Many centers reduce the aspirin dose once the patient is afebrile, even before treating said patient with IVIG. However, a randomized controlled trial regarding high-dose aspirin in the acute stage of KD has not previously been carried out.

Methods/design: This trial has been designed as a multi-center, prospective, randomized controlled, evaluator-blinded trial with two parallel groups to determine whether IVIG alone as the primary therapy in acute-stage KD is as effective as IVIG combined with high-dose aspirin therapy. The primary endpoint is defined as CAL formation at 6-8 weeks. Patients meeting the eligibility criteria are randomly assigned (1:1) to a test group (that receives only IVIG) or a standard group (that receives IVIG plus high-dose aspirin). This clinical trial is conducted at seven medical centers in Taiwan.

Discussion: Since high-dose aspirin has significant anti-inflammatory and anti-platelet functions, it does not appear to lower the frequency of disease outcomes. Furthermore, it can decrease hemoglobin levels. Therefore, the investigators have initiated this randomized controlled trial to determine whether high-dose aspirin is necessary in the acute stage of KD.

Study Timeline

• Study Start: 2016-09
• Study First Submitted: 2016-10-28
• Study First Submitted QC: 2016-10-28
• Study First Posted: 2016-11-01
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-05
• Last Update Posted: 2018-03-06
• Primary Completion: 2019-08
• Study Completion: 2019-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 278

Inclusion Criteria

1. Male or female, under the age of 7 years old.

2. Fulfilled the AHA criteria for KD as explained below:

3. Fever (more than 38.0℃ ear temperature) > or = 5 days, as well as 4 of the 5 following symptoms

4. Diffuse mucosal inflammation (strawberry tongue, dry and cracked lips)

5. Bilateral non-purulent conjunctivitis

6. Dysmorphous skin rashes

7. Indurative edematous change over the hands and feet, or desquamation over the fingertips or toes

8. Cervical lymphadenopathy (one or more nodule at least 1.5 cm in diameter)

9. An informed consent form (ICF, appendix B) signed by the patient or a legal guardian.

Exclusion Criteria

1. Had symptoms that did not completely match the KD criteria.

2. Had an acute fever for < 5 days and >10 days

3. IVIG treatment at another hospital before being referred to the study center.

4. Treatment with corticosteroids, other than the inhaled form, in the two weeks prior to joining the study;

5. The presence of a disease known to mimic Kawasaki disease (such as adenovirus infection, toxic shock syndrome etc.).

6. Previous KD diagnosis.

7. Inability to take aspirin (such as history of hypersensitivity to aspirin, G6PD deficiency, recent herpes zoster infection or vaccination, etc.)

8. Afebrile prior to enrollment

9. CAL prior to enrollment

10. Severe concomitant medical disorders (e.g., immunodeficiency, chromosomal anomalies, congenital heart diseases, metabolic diseases, nephritis, collagen diseases, etc.)

11. Suspected to have an infectious disease, including sepsis, septic meningitis, peritonitis, bacterial pneumonia, varicella, and influenza

12. Judged by the researcher to be unsuitable for this trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IVIG and Aspirin	IVIG and Aspirin	All patients will receive IVIG (2g/kg) in 10-12 hours plus high-dose aspirin (80-100mg/kg/day, divided into four doses) till fever subside. After fever subsides, low-dose aspirin (3-5mg/kg/day) will be prescribed until 6-8 weeks.
IVIG only	IVIG only	All patients will receive IVIG (2g/kg) in 10-12 hours alone, without high-dose aspirin. After fever subsides, low-dose aspirin (3-5mg/kg/day) will be prescribed until 6-8 weeks.

Primary Outcome Measures

Name	Time	Method
coronary artery lesions	8 weeks

Secondary Outcome Measures

Name	Time	Method
IVIG resistance	7 days

Trial Locations

Locations (5)

Linkou Chang Gung Memorial Hospital; 🇨🇳 Taipei, Taiwan

Kaohsiung Veterans General Hospital; 🇨🇳 Kaohsiung, Taiwan

Tungs' Taichung Metroharbor Hospital; 🇨🇳 Taichung, Taiwan

Kaohsiung Chang Gung Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan