Effectiveness and Safety of Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C

NCT ID: NCT04952207

Last Updated: 2021-07-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-03-06

Study Completion Date

2021-08-31

Brief Summary

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Clinical trials evaluating DAA have shown excellent rates of SVR and good safety profiles in patients with CHC infection. Real world data from TARGET, TRIO, IFI, DHCR, DALTON-C, as well as those cohorts from Japan, Taiwan and Korea further confirmed clinical trial findings of DAA in routine practice where populations are more complex. However, these populations are different from Chinese for different host and virus characteristics which limit the applicability of results to local practice.

As DAA launched in China since 2017, the availability of INF free DAA treatment will likely lead to better treatment outcome in routine practice, but there are currently no data available to test the hypothesis.

In clinical practice, the uptake of DAA regimen will depend on a combination of physician preference, patient's characteristics and drug access. This study will also identify how these three variables affect DAA regimen uptake.

This study to 1) characterize pts receiving IFN free DAA regimens, 2) represent common practice in China, 3) describe outcome of various INF free DAA therapy, and 4) confirm registration study results.

Detailed Description

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Chronic Hepatitis C (hereinafter referred to as "CHC") is a viral hepatitis caused by the infection of Hepatitis C virus (HCV). In 2007, a cross-sectional study in six cities showed that the prevalence of HCV was 0.58% in China. It was estimated that there were about 10 million HCV patients in our country. If hepatitis C was not treated in time, about 75% of patients would progress into chronic hepatitis C six months after virus infection; the probability was 5%\~15% for progression into cirrhosis and 2%\~4% for progression into hepatocellular carcinoma 20 years after the infection of chronic hepatitis C. One analysis of cirrhosis etiology in northern China found that the proportion of CHC-induced cirrhosis was increased from 6.39% in 2002 to 13.91% in 2011.

As a result of the severely epidemiological burden of CHC, the World Health Organization (WHO) has established a target to eliminate the hepatitis harm in 2030 ("2030 global targets" for short) that 90% reduction in new cases of chronic hepatitis B and C in 2030, 80% of treatment-eligible people with chronic hepatitis B and C treated and 65% reduction in hepatitis B and C deaths. As a part of the strategy to achieve this target, WHO includes the treatment with direct-acting antiviral agents (DAAs) into the 2017 Essential Medicine List. In addition, the Viral Hepatitis Prevention and Control Programs in China (2017-2020) also emphasize the application of more effective treatment as a part of the strategy to reduce the transmission of HCV.

Direct-acting antiviral agents (DAAs) are a new drug for the treatment of CHC now. In 2017, China Food and Drug Administration (CFDA)/ National Medical Products Administration (NMPA) approved the marketing of Sofosbuvir of Gilead, Ombitasvir/Paritaprevir/Ritonavir Tablets + Dasabuvir of AbbVie, Daclatasvir Tablets + Asunaprevir Capsules of Bristol-Myers Squibb; Elbasvir/Grazoprevir of MSD, Sofosbuvir/Velpatasvir and Ledipasvir/Sofosbuvir of Gilead and Danoprevir of Ascletis in 2018. Before the DAAs are marketed, the pegylated interferon combined with ribavirin (PR) therapy is the major therapy of antiviral for HCV-infected patients. However, the real-world study showed that the sustained virological response (SVR) of PR therapy was 71.1%. The DAAs therapy was demonstrated with shorter treatment time, better efficacy, fewer adverse events, and higher compliance compared with the PR therapy.

Multiple clinical trials indicated a high SVR rate and safety of DAAs in CHC patients. The real-world studies with more complicated patient populations, including TARGET, TRIO, IFI, DHCR, and DALTON-C as well as the cohort studies from Japan, Taiwan, and the Republic of Korea also further demonstrated good clinical efficacy with DAAs. While GT 1-3 is prevalent worldwide, subtypes of 1b, 2a, 3a, 3b, and 6a are prevalent in China, and among them, GT 3 and 6 are expanding. Since the host and virus characteristics of these populations are different from the Chinese population, the BMI of the Chinese population is smaller than that of the European and American population, IL28 CC GT is predominant, and HCV patients of GT 3b is most common among HCV patients of GT 3. So, it is necessary to further demonstrate the applicability of the results of these studies to Chinese patients.

DAAs have been marketed in China since 2017. The treatment with DAAs unnecessary to combine with any interferon (IFN) may obtain better therapeutic effect in clinical practice. However, there is a lack of real-world data to verify this hypothesis now.

In clinical practice, the selection of therapy with DAAs will depend on the physician preference, patient baseline characteristics, and drug accessibility. This study will also determine the baseline status of patients receiving different DAA treatments and possible reasons for doctors' prescriptions in the real world.

In the eastern part of China, the GTs of HCV infected patients are GT 1b (69.2%), GT 2a (20.8%), GT 3a (2.2%), GT 3b (4.4%) and GT 6 (3.2%).To demonstrate whether DAAs provide good efficacy and safety to the patients, including the patients with cirrhosis, accompanying with infection, kidney/liver transplantation, or no response to PR therapy, the purpose of this study is to 1) describe the patient characteristics for DAA therapy unnecessary to combine with any IFN in routine clinical practice in China; 2) describe the therapeutic effect of multiple DAAs unnecessary to combine with any IFN to verify above hypothesis.

Conditions

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Hepatitis C, Chronic

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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DAA Group

Chronic hepatitis C patients treated with DAA

Direct-acting antiviral agents

Intervention Type DRUG

The initial DAA treatment and its dose for all patients is determined by the infectionist or hepatologist based on the clinical diagnosis and treatment routine. The administration dose in the instructions for use for current DAAs marketed in China Mainland unnecessary to combine with any IFN is shown but not limited as follows: Sofosbuvir, Ombitasvir/Paritaprevir/Ritonavir, Dasabuvir, Daclatasvir, Asunaprevir, Elbasvir/Grazoprevir, Sofosbuvir/Velpatasvir and Ledipasvir/Sofosbuvir.

Interventions

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Direct-acting antiviral agents

The initial DAA treatment and its dose for all patients is determined by the infectionist or hepatologist based on the clinical diagnosis and treatment routine. The administration dose in the instructions for use for current DAAs marketed in China Mainland unnecessary to combine with any IFN is shown but not limited as follows: Sofosbuvir, Ombitasvir/Paritaprevir/Ritonavir, Dasabuvir, Daclatasvir, Asunaprevir, Elbasvir/Grazoprevir, Sofosbuvir/Velpatasvir and Ledipasvir/Sofosbuvir.

Intervention Type DRUG

Other Intervention Names

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daclatasvir asunaprevir ombitasvir paritaprevir dasabuvir sofosbuvir velpatasvir ledipasvir elbasvir grazoprevir danoprevir glecaprevir pibrentasvir voxilaprevir

Eligibility Criteria

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Inclusion Criteria

* All Chronic hepatitis C patients to be treated with the DAAs approved by CFDA/NMPA
* Age≄18 years

Exclusion Criteria

* Patients experienced with DAAs
* Documented HCC, AFP\>500ng/ml
* Unlikely to survive 1 year or inability to participate and follow up for the study period
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

Tigermed Consulting Co., Ltd

INDUSTRY

Sponsor Role collaborator

Qing XIe

OTHER

Sponsor Role lead

Responsible Party

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Qing XIe

Director of Department of Infectious Disease, Rui Jin Hospital

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Qing Xie, MD

Role: PRINCIPAL_INVESTIGATOR

Director of Department of Infectious Disease, Rui Jin Hospital

Locations

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Changzhou Third People's Hospital

Changzhou, Jiangsu, China

Site Status RECRUITING

The Second Hospital of Nanjing

Nanjing, Jiangsu, China

Site Status RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

The Fifth People's Hospital of Suzhou

Suzhou, Jiangsu, China

Site Status RECRUITING

Wuxi No. 5 People's Hospital

Wuxi, Jiangsu, China

Site Status RECRUITING

Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Huashan Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

The First Hospital of Jiaxing

Jiaxing, Zhejiang, China

Site Status RECRUITING

Hwa Mei Hospital

Ningbo, Zhejiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Qing Xie, MD

Role: CONTACT

008613651804273

Lichang Chen, MD

Role: CONTACT

008618817555940

Facility Contacts

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Longgen Liu, MD

Role: primary

008613606140932

Yongfeng Yang, MD

Role: primary

008613951990210

Chao Wu, MD

Role: primary

008613809022921

Jun Li, MD

Role: primary

008613905175333

Chuanwu Zhu, MD

Role: primary

008613606202525

Lihua Huang, MD

Role: primary

008613601513551

Qing Xie, MD

Role: primary

008613651804273

Lichang Chen, MD

Role: backup

008618817555940

Jiming Zhang, MD

Role: primary

008613816317838

Liang Chen, MD

Role: primary

008618930810000

Xinsheng Xie, MD

Role: primary

008613615833233

Hao Ying, MD

Role: primary

008613806663345

References

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Lu J, Zhou Y, Lin X, Jiang Y, Tian R, Zhang Y, Wu J, Zhang F, Zhang Y, Wang Y, Bi S. General epidemiological parameters of viral hepatitis A, B, C, and E in six regions of China: a cross-sectional study in 2007. PLoS One. 2009 Dec 24;4(12):e8467. doi: 10.1371/journal.pone.0008467.

Reference Type BACKGROUND
PMID: 20041146 (View on PubMed)

Chen YS, Li L, Cui FQ, Xing WG, Wang L, Jia ZY, Zhou MG, Gong XH, Wang FZ, Zheng H, Luo HM, Bi SL, Wang N, Yang WZ, Liang XF. [A sero-epidemiological study on hepatitis C in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2011 Sep;32(9):888-91. Chinese.

Reference Type BACKGROUND
PMID: 22340876 (View on PubMed)

Rao HY, Li H, Chen H, Shang J, Xie Q, Gao ZL, Li J, Sun Y, Jiang J, Wang L, Zhao L, Zhang L, Yang W, Niu J, Gong Z, Gong G, Yang R, Lee MH, Wei L. Real-world treatment patterns and clinical outcomes of HCV treatment-naive patients in China: an interim analysis from the CCgenos study. J Gastroenterol Hepatol. 2017 Jan;32(1):244-252. doi: 10.1111/jgh.13467.

Reference Type BACKGROUND
PMID: 27289083 (View on PubMed)

Lu L, Nakano T, He Y, Fu Y, Hagedorn CH, Robertson BH. Hepatitis C virus genotype distribution in China: predominance of closely related subtype 1b isolates and existence of new genotype 6 variants. J Med Virol. 2005 Apr;75(4):538-49. doi: 10.1002/jmv.20307.

Reference Type BACKGROUND
PMID: 15714489 (View on PubMed)

Chen Y, Yu C, Yin X, Guo X, Wu S, Hou J. Hepatitis C virus genotypes and subtypes circulating in Mainland China. Emerg Microbes Infect. 2017 Nov 1;6(11):e95. doi: 10.1038/emi.2017.77.

Reference Type BACKGROUND
PMID: 29089588 (View on PubMed)

Ogawa E, Furusyo N, Murata M, Hayashi T, Shimizu M, Mukae H, Toyoda K, Hotta T, Uchiumi T, Hayashi J. Impact of HCV kinetics on treatment outcome differs by the type of real-time HCV assay in NS3/4A protease inhibitor-based triple therapy. Antiviral Res. 2016 Feb;126:35-42. doi: 10.1016/j.antiviral.2015.12.001. Epub 2015 Dec 12.

Reference Type BACKGROUND
PMID: 26692214 (View on PubMed)

Matthews SJ, Lancaster JW. Telaprevir: a hepatitis C NS3/4A protease inhibitor. Clin Ther. 2012 Sep;34(9):1857-82. doi: 10.1016/j.clinthera.2012.07.011. Epub 2012 Aug 28.

Reference Type BACKGROUND
PMID: 22951253 (View on PubMed)

Heo YA, Deeks ED. Sofosbuvir/Velpatasvir/Voxilaprevir: A Review in Chronic Hepatitis C. Drugs. 2018 Apr;78(5):577-587. doi: 10.1007/s40265-018-0895-5.

Reference Type BACKGROUND
PMID: 29546556 (View on PubMed)

Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16.

Reference Type BACKGROUND
PMID: 26571066 (View on PubMed)

Other Identifiers

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IN-CN-342-5424

Identifier Type: -

Identifier Source: org_study_id

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