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Lancet. 2019 Mar 16;393(10176):1128-1137. doi: 10.1016/S0140-6736(18)32003-8. Epub 2019 Mar 7.

Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial.

Author information

1
Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Pediatrics, Yachiyo Medical Center, Tokyo Women's Medical University, Chiba, Japan.
2
Department of Pediatrics, Wakayama Medical University of Medicine, Wakayama, Japan.
3
Department of Public Health, Chiba University, Chiba, Japan.
4
Department of Pediatrics, Chiba University, Chiba, Japan.
5
Department of Pediatrics, Yachiyo Medical Center, Tokyo Women's Medical University, Chiba, Japan.
6
Department of Pediatrics, NTT Sapporo Medical Center, Sapporo, Japan.
7
Department of Pediatrics, Chiba Cardiovascular Center, Chiba, Japan.
8
Oriono Clinic, Sakai, Japan.
9
Department of Pediatrics, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan.
10
Department of Pediatrics, Showa University Northern Yokohama Hospital, Yokohama, Japan.
11
Department of Pediatric Cardiology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
12
Department of Pediatrics, National Center for Global Health and Medicine, Tokyo, Japan.
13
Department of Pediatrics, Kimitsu Chuo Hospital, Chiba, Japan.
14
Department of Pediatrics, Kumamoto Regional Medical Center, Kumamoto, Japan.
15
Department of Pediatrics, Funabashi Municipal Medical Center, Funabashi, Japan.
16
Department of Pediatric Cardiology, Okinawa Prefectural Nanbu Medical Center and Children's Medical Center, Okinawa, Japan.
17
Department of Pediatrics, Nihon University Itabashi Hospital, Tokyo, Japan.
18
Department of Pediatrics, Ehime Prefectural Central Hospital, Ehime, Japan.
19
Department of Pediatrics, Kagoshima City Hospital, Kagoshima, Japan.
20
Department of Pediatrics, Takatsuki General Hospital, Osaka, Japan.
21
Department of Pediatrics, Kawasaki Medical School Hospital, Okayama, Japan.
22
Department of General Pediatrics & Interdisciplinary Medicine, National Center for Child Health and Development, Tokyo, Japan.
23
Department of Pediatrics, Toho University, Tokyo, Japan.
24
Department of Pediatrics, Graduate School of Medicine, University of Toyama, Toyama, Japan.
25
Department of Pediatrics, Hokkaido University Hospital, Sapporo, Japan.
26
Department of Regional Pediatrics and Perinatology, Graduate School of Medicine, Ehime University, Ehime, Japan.
27
Department of Pediatrics, Komatsu Municipal Hospital, Ishikawa, Japan.
28
Clinical Research Centre, Chiba University Hospital, Chiba, Japan.
29
Department of Pediatrics, Funabashi Municipal Medical Center, Funabashi, Japan; Clinical Research Centre, Chiba University Hospital, Chiba, Japan.
30
Department of Public Health, Chiba University, Chiba, Japan. Electronic address: ahata@faculty.chiba-u.jp.

Erratum in

Abstract

BACKGROUND:

Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities.

METHODS:

We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174.

FINDINGS:

We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0·46; 95% CI 0·25-0·86; p=0·010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0·78).

INTERPRETATION:

Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG.

FUNDING:

Japan Agency for Medical Research and Development (grant CCT-B-2503).

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