Effects of immunoglobulin plus prednisolone in reducing coronary artery lesions in patients with Kawasaki disease: study protocol for a phase III multicenter, open-label, blinded-endpoints randomized controlled trial

Si-Yuan Lin, Lan He, Li-Ping Xie, Yin Wang, Yi-Xiang Lin, Yin-Yin Cao, Wei-Li Yan, Fang Liu, Guo-Ying Huang, Si-Yuan Lin, Lan He, Li-Ping Xie, Yin Wang, Yi-Xiang Lin, Yin-Yin Cao, Wei-Li Yan, Fang Liu, Guo-Ying Huang

Abstract

Background: Kawasaki disease (KD) is an acute systemic vasculitis of unclear etiology that mainly affects infants and young children. Strategies to reduce the incidence and severity of coronary artery lesions (CALs), the determinant factor in the long-term prognosis of KD, are currently a focus of studies on KD. Corticosteroids, preferred in the treatment of the majority of vasculitides, are controversial in the treatment of acute KD. In this trial, we will evaluate whether the addition of prednisolone to standard intravenous immunoglobulin (IVIG) plus aspirin therapy can reduce the occurrence of CAL in Chinese patients with KD.

Methods: This is a multicenter, prospective, open-label, randomized controlled trial, which is expected to be conducted in more than 20 hospitals in China and aims to assess the efficacy and safety of IVIG + prednisolone treatment versus standard treatment. Patients with KD who fulfill the inclusion and exclusion criteria will be recruited and randomized (1:1) to receive either a large dose of IVIG (2 g/kg over 12-24 h with a maximum dose of 60 g) + aspirin 30 mg/kg/d or IVIG (2 g/kg over 12-24 h) + aspirin 30 mg/kg/d + prednisolone (2 mg/kg/d with a maximum dose of 60 mg tapered over 15 days after normalization of C-reactive protein concentration). The primary outcome will be the occurrence of CAL at 1 month of illness. The follow-up duration for each participant will be set as 1 year. Patients and treating physicians will be unmasked to group allocation.

Discussion: This will be the first multicenter randomized controlled trial to evaluate the efficacy of IVIG + aspirin + prednisolone in Chinese pediatric patients with KD, which may provide high-level evidence for improving the initial treatment for acute KD.

Trial registration: ClinicalTrials.gov NCT04078568 . Registered on 16 August 2018.

Keywords: Coronary artery lesions; Corticosteroid; Kawasaki disease; Primary treatment.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Diagram of the study design. CAL, coronary artery lesion; CRP, C-reactive protein; IVIG, intravenous immunoglobulin; KD, Kawasaki disease
Fig. 2
Fig. 2
Schedule of enrolment, intervention, and assessment. a Gray shading shows the primary endpoint. b It is inferred experientially that CRP levels may become normal 3 days after IVIG completion when the patient switches from intravenous methylprednisolone to oral prednisolone tapered over 15 days. c Patients will accept rescue therapy if they exhibit IVIG resistance. d Axillary temperature (or rectal temperature) will be measured every 6 h from IVIG treatment. The time point, temperature, and treatment will be recorded if fever occurs between two measurements. When IVIG starts and body temperature becomes normal it will be recorded. e Laboratory examination includes CRP, ESR, Hct, Hb, ALB, SAA, prealbumin, ALT, AST, CK-MB, sodium, NT-proBNP, IL-2, IL-4, IL-6, IL-10, TNF-α, TB, troponin, D-dimer, lipid, and lipoprotein serum levels and WBC, NEUT, and PLT counts. CRP and routine blood tests will be measured every 3 days after completion of initial IVIG infusion until normal. The remaining indicators (except for ESR), if abnormal, will also be measured every 3 days after completion of initial IVIG infusion until normal. f Other auxiliary examination includes electrocardiogram, chest radiography, magnetic resonance angiography, and myocardial perfusion imaging. The patient will choose whether to accept the examinations based on the physical condition during the diagnostic and therapeutic period. ALB, serum albumin; ALT, alanine aminotransferase; AST, aspartate transaminase; CK-MB, creatine kinase-muscle/brain; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; Hb, hemoglobin; Hct, hematocrit; IL-2, interleukin-2; IL-4, interleukin-4; IL-6, interleukin-6; IL-10, interleukin-10; IVIG, intravenous immunoglobulin; NEUT, neutrophil; NT-proBNP, N-terminal pro-B-type natriuretic peptide, PLT, platelet; SAA, serum amyloid A; TB, total bilirubin; TNF-α, tumor necrosis factor-alpha; WBC, white blood cell

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