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

NCT ID: NCT02951234

Last Updated: 2018-03-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 278 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2019-08-31

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.

Conditions

Kawasaki Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

IVIG only

Intervention Type: OTHER

All patients will receive IVIG (2g/kg) in 10-12 hours alone, without high-dose 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.

Group Type: ACTIVE_COMPARATOR

IVIG and Aspirin

Intervention Type: OTHER

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.

Interventions

IVIG only

All patients will receive IVIG (2g/kg) in 10-12 hours alone, without high-dose aspirin.

Intervention Type: OTHER

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

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

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

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

3. Bilateral non-purulent conjunctivitis

4. Dysmorphous skin rashes

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

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

3. 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.

-

• Maximum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ho-Chang Kuo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital

Locations

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

Site Status: RECRUITING

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status: RECRUITING

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status: RECRUITING

Tungs' Taichung Metroharbor Hospital

Taichung, , Taiwan

Site Status: RECRUITING

Linkou Chang Gung Memorial Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Ho-Chang Kuo, MD, PhD

Role: CONTACT

erickuo48@yahoo.com.tw

Ying-Hsien Huang, MD, PhD

Role: CONTACT

yhhuang123@yahoo.com.tw

Facility Contacts

Ken-Pen Weng, MD

Role: primary

kenpenweng@yahoo.com.tw

+886-975581955

Ho-Chang Kuo, MD, PhD

Role: primary

erickuo48@yahoo.com.tw

Ying-Hsien Huang, MD, PhD

Role: backup

yhhuang123@yahoo.com.tw

Ming-Chih Lin, MD

Role: primary

mingclin@gmail.com

+886-917620556

Chung-Chih Kao, MD

Role: primary

cckao2cv@yahoo.com

+886-935279276

Chih-Jung Chen, MD

Role: primary

chinjung@adm.cgmh.org.tw

References

Kuo HC, Lin MC, Kao CC, Weng KP, Ding Y, Han Z, Chen CJ, Jan SL, Chien KJ, Ko CH, Lin CY, Lei WT, Guo MM, Yang KD, Sylvester KG, Whitin JC, Tian L, Chubb H, Ceresnak SR, McElhinney D, Cohen HJ, Ling XB. Intravenous Immunoglobulin Alone for Coronary Artery Lesion Treatment of Kawasaki Disease: A Randomized Clinical Trial. JAMA Netw Open. 2025 Apr 1;8(4):e253063. doi: 10.1001/jamanetworkopen.2025.3063.

Reference Type: DERIVED

PMID: 40178858 (View on PubMed)

Kuo HC, Lin MC, Kao CC, Weng KP, Ding Y, Chen CJ, Jan SL, Chien KJ, Ko CH, Lin CY, Lei WT, Chang LS, Guo MM, Yang KD, Sylvester KG, Han Z, Whitin JC, Tian L, Chubb H, Ceresnak SR, McElhinney D, Cohen HJ, Ling XB. EFFICACY OF INTRAVENOUS IMMUNOGLOBULIN ALONE ON CORONARY ARTERY LESION REDUCTION IN KAWASAKI DISEASE. medRxiv [Preprint]. 2024 Jul 12:2024.07.11.24310310. doi: 10.1101/2024.07.11.24310310.

Reference Type: DERIVED

PMID: 39040184 (View on PubMed)

Kuo HC, Guo MM, Lo MH, Hsieh KS, Huang YH. Effectiveness of intravenous immunoglobulin alone and intravenous immunoglobulin combined with high-dose aspirin in the acute stage of Kawasaki disease: study protocol for a randomized controlled trial. BMC Pediatr. 2018 Jun 22;18(1):200. doi: 10.1186/s12887-018-1180-1.

Reference Type: DERIVED

PMID: 29933749 (View on PubMed)

Other Identifiers

IVIG And Aspirin in KD

Identifier Type: -

Identifier Source: org_study_id