Clinical trial NCT02951234: A Multi-center, Randomized to Compare the Efficacy of IVIG Alone and IVIG Plus High-dose Aspirin in Kawasaki Disease
Official title: Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Kawasaki Disease
Keywords: coronary artery lesions
intravenous immunoglobulin
Kawasaki disease
randomized clinical trial
aspirin
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2016-11-01
Enrollment: 278
Sex: ALL
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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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.

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Primary outcomes:
measure: coronary artery lesions
timeFrame: 8 weeks
Secondary outcomes:
measure: IVIG resistance
timeFrame: 7 days
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taichung
country: Taiwan
facility: Tungs' Taichung Metroharbor Hospital
city: Taipei
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital
name: Ho-Chang Kuo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.