Murata Yo, Isayama Reina, Imai Shoko, Shoji Kensuke, Youndzi Mizuho, Okada Mami, Mikami Masashi, Kobayashi Shinobu, Urayama Kevin Y, Kobayashi Tohru
Center for Postgraduate Education and Training, National Center for Child Health and Development, Tokyo, Japan.
Department of Data Science, Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan.
Contemp Clin Trials Commun. 2022 Jan 20;26:100892. doi: 10.1016/j.conctc.2022.100892. eCollection 2022 Apr.
Kawasaki disease (KD) is a systemic vasculitis complicated with coronary artery abnormalities (CAAs). Intravenous immunoglobulin reduces the occurrence of CAAs, but significant number of KD patients with CAAs still exists. Thus, new approaches to prevent and attenuate CAAs are warranted. Atorvastatin has been shown to promote endothelial cell homeostasis and suppress vascular inflammation and has received enthusiasm as a potentially new candidate treatment for KD. In the United States, a phase I/IIa dose-escalation study of atorvastatin in KD patients with CAAs demonstrated the safety and pharmacokinetic data of atorvastatin. However, due to the uncertainty in the application of these results to other populations, we aim to examine the tolerability and generate pharmacokinetics data in Japanese KD patients.
This is a multicenter, single-arm, open-label, phase I/IIa study of atorvastatin in acute KD patients with CAAs in Japan. A minimum of 9 and a maximum of 18 KD patients (2 years-17 years old) will be recruited for a 3 + 3 dose-escalation study of a 6-week course of atorvastatin (0.125-0.5 mg/kg/day). The primary outcome will be safety of atorvastatin. The secondary outcomes will be pharmacokinetics of atorvastatin, activity of atorvastatin and echocardiographic assessment of CAAs. The activity of atorvastatin will include assessment of C-reactive protein or high sensitivity C-reactive protein and white blood cell levels.
This study will provide evidence of the safety, tolerability, and pharmacokinetics of atorvastatin in Japanese KD patients and may lead new standard therapy for acute-phase KD associated with CAA complications.
Japan Registry of Clinical Trials (JRCTs031180057). Registered December 19, 2018, https://jrct.niph.go.jp/en-latest-detail/jRCTs031180057.
川崎病（KD）是一种伴有冠状动脉异常（CAA）的系统性血管炎。静脉注射免疫球蛋白可降低CAA的发生率，但仍有相当数量的KD患者出现CAA。因此，需要新的方法来预防和减轻CAA。阿托伐他汀已被证明可促进内皮细胞稳态并抑制血管炎症，并作为KD潜在的新候选治疗方法受到关注。在美国，一项针对患有CAA的KD患者的阿托伐他汀I/IIa期剂量递增研究证明了阿托伐他汀的安全性和药代动力学数据。然而，由于将这些结果应用于其他人群存在不确定性，我们旨在研究日本KD患者对阿托伐他汀的耐受性并生成药代动力学数据。
这是一项在日本对患有CAA的急性KD患者进行的阿托伐他汀多中心、单臂、开放标签的I/IIa期研究。将招募至少9名且最多18名KD患者（2岁至17岁），进行为期6周的阿托伐他汀（0.125 - 0.5mg/kg/天）3 + 3剂量递增研究。主要结局将是阿托伐他汀的安全性。次要结局将包括阿托伐他汀的药代动力学、阿托伐他汀的活性以及CAA的超声心动图评估。阿托伐他汀的活性将包括对C反应蛋白或高敏C反应蛋白以及白细胞水平的评估。
本研究将提供阿托伐他汀在日本KD患者中的安全性、耐受性和药代动力学证据，并可能引领针对伴有CAA并发症的急性期KD的新的标准治疗方法。
日本临床试验注册中心（JRCTs031180057）。于2018年12月19日注册，https://jrct.niph.go.jp/en-latest-detail/jRCTs031180057 。
