Pemafibrate for treating MASLD complicated by hypertriglyceridaemia: a multicentre, open-label, randomised controlled trial study protocol

被引：2

作者：

Iwaki, Michihiro ^{[1
]}

Kobayashi, Takashi ^{[1
]}

Nogami, Asako ^{[1
]}

Ogawa, Yuji ^{[2
]}

Imajo, Kento ^{[3
]}

Sakai, Eiji ^{[4
]}

Nakada, Yoshinobu ^{[5
]}

Koyama, Satoshi ^{[6
]}

Kurihashi, Takeo ^{[7
]}

Oza, Noriko ^{[8
]}

Kohira, Toshikazu ^{[9
]}

Okada, Michiaki ^{[10
]}

Yamaguchi, Yuki ^{[11
]}

Iwane, Shinji ^{[12
]}

Kageyama, Fujito ^{[13
]}

Sasada, Yuzo ^{[14
]}

Matsushita, Masahiro ^{[15
]}

Tadauchi, Akimitsu ^{[16
]}

Murohisa, Gou ^{[17
]}

Nagasawa, Masamichi ^{[17
]}

Sato, Shuichi ^{[18
]}

Maeda, Kazuhisa ^{[19
]}

Furuta, Koichiro ^{[20
]}

Shigefuku, Ryuta ^{[21
]}

Seko, Yuya ^{[22
]}

Tobita, Hiroshi ^{[23
]}

Kawata, Kazuhito ^{[24
]}

Kawanaka, Miwa ^{[25
]}

Sugihara, Takaaki ^{[26
]}

Tamaki, Nobuharu ^{[27
]}

Iwasa, Motoh ^{[21
]}

Kawaguchi, Takumi ^{[28
]}

Itoh, Yoshito ^{[22
]}

Kawaguchi, Atsushi ^{[29
]}

Takahashi, Hirokazu ^{[30
]}

Nakajima, Atsushi ^{[1
]}

Yoneda, Masato ^{[1
]}

机构：

[1] Yokohama City Univ, Sch Med, Dept Gastroenterol & Hepatol, Grad Sch Med, Yokohama, Kanagawa, Japan

[2] Natl Hosp Org Yokohama Med Ctr, Dept Gastroenterol, Yokohama, Kanagawa, Japan

[3] Shin Yurigaoka Gen Hosp, Dept Gastroenterol, Kawasaki, Kanagawa, Japan

[4] Yokohama Sakae Kyosai Hosp, Dept Gastroenterol, Yokohama, Kanagawa, Japan

[5] Shonan Hosp, Dept Internal Med, Yokosuka, Kanagawa, Japan

[6] NamikiKoiso Med Clin, Dept Internal Med, Yokohama, Kanagawa, Japan

[7] Kanagawa Dent Univ, Dept Internal Med, Yokohama Clin, Yokohama, Kanagawa, Japan

[8] Saga Prefecture Med Ctr Koseikan, Dept Hepatobiliary Pancreatol, Saga, Saga, Japan

[9] Loco Med Gen Inst, Saga, Japan

[10] Karatsu Red Cross Hosp, Dept Internal Med, Karatsu, Japan

[11] Masuda Red Cross Hosp, Dept Internal Med, Masuda, Japan

[12] Fujioka Hosp, Dept Internal Med, Saga, Japan

[13] Hamamatsu Med Ctr, Dept Gastroenterol & Hepatol, Hamamatsu, Shizuoka, Japan

[14] Iwata City Hosp, Dept Hepatol, Iwata, Japan

[15] Shimada Municipal Hosp, Dept Gastroenterol, Shizuoka, Japan

[16] Seirei Mikatahara Byoin, Dept Gastroenterol, Hamamatsu, Shizuoka, Japan

[17] Seirei Hamamatsu Byoin, Dept Gastroenterol, Hamamatsu, Shizuoka, Japan

[18] Izumo City Gen Med Ctr, Dept Internal Med, Izumo, Shimane, Japan

[19] Kitasenri Maeda Clin, Dept Internal Med, Suita, Osaka, Japan

[20] Natl Hosp Org Hamada Med Ctr, Dept Gastroenterol, Hamada, Japan

[21] Mie Univ, Dept Gastroenterol & Hepatol, Fac Med, Grad Sch Med, Tsu, Mie, Japan

[22] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Mol Gastroenterol & Hepatol, Kyoto, Japan

[23] Shimane Univ Hosp, Div Hepatol, Shimane, Japan

[24] Hamamatsu Univ Sch Med, Hepatol Div, Dept Internal Med 2, Hamamatsu, Shizuoka, Japan

[25] Kawasaki Med Ctr, Kawasaki Med Sch, Dept Gen Internal Med 2, Kurashiki, Okayama, Japan

[26] Tottori Univ, Div Med & Clin Sci, Dept Multidisciplinary Internal Med, Fac Med,Grad Sch Med, Yonago, Tottori, Japan

[27] Musashino Red Cross Hosp, Dept Gastroenterol & Hepatol, Musashino, Tokyo, Japan

[28] Kurume Univ, Div Gastroenterol, Sch Med, Dept Med, Kurume, Fukuoka, Japan

[29] Saga Univ, Fac Med, Educ & Res Ctr Community Med, Saga, Japan

[30] Saga Univ Hosp, Dept Metab & Endocrinol, Ctr Liver, Saga, Saga, Japan

来源：

BMJ OPEN | 2024年 / 14卷 / 11期

关键词：

Hepatology; Other metabolic; e.g; iron; porphyria; Lipid disorders; PPAR-ALPHA MODULATOR; DOUBLE-BLIND; LIVER; FENOFIBRATE; PLACEBO; DYSLIPIDEMIA; PIOGLITAZONE; BIOPSY; K-877;

D O I：

10.1136/bmjopen-2024-088862

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Introduction Non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated steatotic liver disease (MASLD), is a phenotype of the metabolic syndrome in the liver and is clearly associated with metabolic abnormalities such as hyperglycaemia and dyslipidaemia. Although the prevalence of MASLD is increasing worldwide, there is currently no consensus on the efficacy and safety of the drugs used to treat MASLD/metabolic dysfunction-associated steatohepatitis (MASH). Pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was designed to have higher peroxisome proliferator-activated receptor alfa (PPAR alpha) agonist activity and selectivity than existing PPAR alpha agonists, and in development trials, without increasing creatinine levels, lipid parameters and alanine aminotransferase (ALT) were significantly improved. Thus, pemafibrate may effectively ameliorate the pathogenesis and metabolic abnormalities in MASLD/MASH. In this trial, we evaluated the efficacy and safety of pemafibrate in patients with MASLD/MASH.Methods and analysis This trial was designed as an open-label, three-arm, randomised controlled study. After obtaining informed consent, patients aged 20-80 years who met the selection criteria were enrolled. Patients were randomised to receive pemafibrate 0.4 mg/day, 0.2 mg/day or fenofibrate (n=120 per group). The duration of treatment was 48 weeks. The primary endpoint was a change in ALT levels after 24 weeks of administration. Secondary endpoints included changes from baseline in liver fibrosis markers (fibrosis-4 index, type IV collagen 7s, enhanced liver fibrosis and Mac-2 binding protein glycosylation isomer) at 48 weeks as well as changes in liver fat mass and liver stiffness measured by MRI and ultrasound (US) at centres equipped with MRI and US capabilities.Ethics and dissemination Ethical approval was obtained from the Yokohama City University Certified Institutional Review Board before participant enrolment (CRB20-014). The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences. Participants wishing to understand the results of this study will be contacted directly on data publication.Trial registration number This trial was registered in the Japan Registry of Clinical Trials (number: jRCTs031200280).Protocol version V.1.9, 23 November 2023

引用

页数：11

共 33 条

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