抗纤维化中药扶正化瘀对恩替卡韦治疗2年后持续性晚期纤维

StephenW

Contemp Clin Trials Commun

. 2020 Jun 23;19:100601.
doi: 10.1016/j.conctc.2020.100601. eCollection 2020 Sep.
Safety and Therapeutic Effects of Anti-Fibrotic Traditional Chinese Medicine Fuzheng Huayu on Persistent Advanced Stage Fibrosis Following 2 Years Entecavir Treatment: Study Protocol for a Single Arm Clinical Objective Performance Criteria Trial
Yangyi Chen  1 , Zhimin Zhao  1 , Haina Fan  1 , Zhengxin Li  1 , Yingchun He  1 , Chenghai Liu  1   2
Affiliations

    PMID: 32642592 PMCID: PMC7334581 DOI: 10.1016/j.conctc.2020.100601

Abstract

Background: Hepatitis B virus (HBV) infection is an important etiology for chronic hepatitis globally, and especially so in China. HBV infection can lead to the development of cirrhosis through the pathological process of liver fibrosis. The effective suppression of HBV replication with NAs or interferon-alpha can histologically regress the fibrotic pathological process, but there remain patients who have achieved anti-viral responses and normalization of serum liver tests, but not liver fibrosis regression. This subset of patients typically presents with advanced liver fibrosis at baseline. Therefore, it is reasonable to administer the anti-fibrotic agents, coupled with antivirals for patients with advanced liver fibrosis due to HBV, in order to improve the fibrotic regression of the patients. Fuzheng Huayu (FZHY) tablet is a botanical product with evidence demonstrating its efficacy against mild to moderate liver fibrosis. The current clinical trial evaluates the efficacy and safety of the combination therapy of traditional Chinese medicine (TCM) (FZHY and herbal granule) and entecavir for HBV compensated cirrhosis. We will enroll HBV patients who presented with a good viral response after 2 years of entecavir treatment but had advanced liver fibrosis (≥Ishak F5).

Methods: This is a single-arm clinical trial, conducted in 20 centers in mainland China over a period of 60 weeks, including 48 weeks of treatment observation and 12 weeks of follow-up. The main inclusion criteria include HBsAg positive more than 6 months, 2 years administration of entecavir, HBV DNA less than 20 IU/ml, liver fibrotic stage ≥ F5, and Child-Pugh scoring <7 (Stage A). The sample size is estimated to be about 190, considering a 20% drop-out and 60% of patient's compliance for the second liver biopsy so a total of 350 participants will be enrolled. All eligible participants are divided into 3 subgroups according to the TCM clinic pattern. And all patients will take 1 Entecavir tablet (0.5 mg) per day, 4 FZHY tablets (1.6 g) three times a day, and specific TCM granule three times a day, which is decided by TCM clinical patterns (CPs) differentiation. The patients were treated for 48 weeks, and follow-up visits at 12, 24, 36, 48 weeks and 60 weeks. The patients will receive the second liver biopsy at the end of 48 weeks, with a 12 weeks follow-up after that.The primary endpoint is the proportion of subjects with a 1-point improvement of liver fibrosis stage using the Ishak score from baseline to week 48 in the study, according to consensus readings evaluated by a panel of hepato-pathologists. The secondary endpoints are the brightness-mode ultrasonic, fibrotic biomarkers. The adverse events (AEs) will be recorded for 60 weeks, and the safety of the combination therapy will be evaluated. Meanwhile, the efficacy in the 3 sub-groups will be stratified and analyzed.

Discussion: The study has been designed to test the therapeutic effects and safety of the combination therapy of FZHY and herbal granule with entecavir on persistent advanced stage fibrosis/cirrhosis following 2 years entecavir treatment, and to explore an effective integrative therapy on HBV cirrhosis.

Trial registration: ClinicalTrials.gov. NCT02241616. Registered on September 16, 2014.

Keywords: AEs, adverse events; CPs, Clinical Patterns; CRC, Clinical Research Coodinator; CRO, Central Clinical Research Organization; Cirrhosis; EDC, Electronic Data Collection; Entecavir; FZHY, FuZheng HuaYu; Fuzheng huayu tablet; GMP, Good Manufacturing Practice; HBV, Hepatitis B virus; HSCs, Hepatic Stellate Cells; Hepatitis B virus; Liver fibrosis; NAs, Nucleos(t)ide analogues; NMPA, National Medical Products Administration; OPC, objective performance criteria; PDGF-BB, Platelet Derived Growth Factor-BB; PHBC-PRO, patient reported outcomes of post-hepatitic B cirrhosis; PI, principal investigator; Regression; TCM, Traditional Chinese medicine; TGF-β1, Transforming Growth Factor-beta 1; US FDA, United States Food and Drug Administration; WHO, World Health Organization.

© 2020 Published by Elsevier Inc.
Conflict of interest statement

The authors declare that they have no competing interests.

StephenW

当代临床试验社区

。 2020年6月23日； 19：100601。
doi：10.1016 / j.conctc.2020.100601。 eCollection 2020年9月
抗纤维化中药扶正化瘀对恩替卡韦治疗2年后持续性晚期纤维化的安全性和治疗作用：单臂临床客观性能标准试验的研究方案
陈杨怡1，赵志敏1，范海娜1，李正新1，何应春1，刘澄海1 2
隶属关系

    PMID：32642592 PMCID：PMC7334581 DOI：10.1016 / j.conctc.2020.100601

抽象

背景：乙型肝炎病毒（HBV）感染是全球慢性肝炎的重要病因，在中国尤其如此。 HBV感染可通过肝纤维化的病理过程导致肝硬化的发展。用NAs或干扰素-α有效抑制HBV复制可以从组织学上退缩纤维化的病理过程，但仍有一些患者获得了抗病毒应答和血清肝试验正常化，但肝纤维化没有消退。这部分患者通常在基线时表现为晚期肝纤维化。因此，对于由于HBV而导致的晚期肝纤维化的患者，合理地给予抗纤维化药物和抗病毒药物，以改善患者的纤维化消退。扶正化瘀（FZHY）片是一种植物性产品，有证据表明其对轻度至中度肝纤维化的功效。当前的临床试验评估了中药（FZHY和草药颗粒）和恩替卡韦联合治疗乙肝病毒性肝硬化的疗效和安全性。我们将招募恩替卡韦治疗2年后表现出良好病毒反应但晚期肝纤维化（≥IshakF5）的HBV患者。

方法：这是一项单臂临床试验，在中国大陆的20个中心进行，为期60周，包括48周的治疗观察和12周的随访。主要纳入标准包括6个月以上的HBsAg阳性，恩替卡韦治疗2年，HBV DNA低于20 IU / ml，肝纤维化阶段≥F5和Child-Pugh评分<7（A期）。考虑到第二次肝活检有20％的辍学率和60％的患者依从性，因此样本量估计约为190，因此将招募350名参与者。根据中医诊所模式，将所有符合条件的参与者分为3个亚组。所有患者每天将服用1片恩替卡韦片（0.5毫克），每天3次服用4片FZHY片剂（1.6克），并每天服用3次特定的中药颗粒，这取决于中医临床模式（CP）的差异。患者接受了48周的治疗，并在12、24、36、48周和60周进行了随访。患者将在48周结束时接受第二次肝活检，然后进行12周的随访。根据一组肝病理学家评估的共识性研究，主要终点是研究中从基线到第48周使用Ishak评分在肝纤维化阶段改善1分的受试者的比例。次要终点是亮度模式超声纤维化生物标记物。将记录不良事件（AEs）60周，并评估联合治疗的安全性。同时，将对这三个亚组的疗效进行分层和分析。

讨论：本研究旨在测试FZHY和草药颗粒与恩替卡韦联合治疗恩替卡韦治疗2年后持续性晚期纤维化/肝硬化的疗效和安全性，并探索有效的HBV肝硬化综合疗法。

试用注册：ClinicalTrials.gov。 NCT02241616。 2014年9月16日注册。

关键词：不良事件，不良事件； CP，临床模式； CRC，临床研究顾问；中央临床研究组织CRO；肝硬化； EDC，电子数据收集；恩替卡韦; FZHY，福正华宇；扶正化瘀片； GMP，良好生产规范； HBV，乙型肝炎病毒； HSC，肝星状细胞；乙型肝炎病毒;肝纤维化； NAs，Nucleos（t）ide类似物； NMPA，国家医疗产品管理局； OPC，客观绩效标准； PDGF-BB，血小板衍生生长因子-BB； PHBC-PRO，患者报告了乙肝后肝硬化的结局； PI，首席研究员；回归；中医药； TGF-β1，转化生长因子-β1；美国FDA，美国食品药品监督管理局;世卫组织，世界卫生组织。

©2020由Elsevier Inc.出版
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StephenW

https://www.sciencedirect.com/sc ... 20300855?via%3Dihub

ybdn

99%的中药论文是瞎编的，单位考核用 的

乙肝人1949

职称评审用的。