Clinical trial NCT04952207: Effectiveness and Safety of Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C
Official title: Effectiveness and Safety of Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C: Multi-center, Prospective, Observational Real-world Study in EASTERN China
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatitis C, Chronic
Keywords: Chronic hepatitis C
Direct-acting antiviral agents
Sustained virological response
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: Tigermed Consulting Co., Ltd
First posted: 2021-07-07
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The primary objective of this study is to obtain the SVR12 rate of CHC patients in Eastern China. The previous study of Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine showed that the SVR12 rate was 0.988 (CI 95%: 0.952-1.0, Shanghai, China, Rui Jin Hospital, 26th APASL annual meeting, PO241). In this study, the estimated value of SVR is set to 95%, the bilateral significance level is 0.05 and the sampling error is 0.03. The estimated sample size is 225 as per the sample size calculation formula. Considering the patient withdrawal, this study is planned to collect 300 patients.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: SVR12 rate of DAA
timeFrame: 12 weeks after the treatment with DAA regimen
Secondary outcomes:
Other outcomes:
Locations:
city: Changzhou
country: China
facility: Changzhou Third People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Fifth People's Hospital of Suzhou
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi No. 5 People's Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
city: Jiaxing
country: China
facility: The First Hospital of Jiaxing
state: Zhejiang
city: Ningbo
country: China
facility: Hwa Mei Hospital
state: Zhejiang
Study officials:
affiliation: Director of Department of Infectious Disease, Rui Jin Hospital
name: Qing Xie, MD
role: PRINCIPAL_INVESTIGATOR
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