A Korean Cohort Study of TDF Rescue Therapy for Difficult-to-treat CHB Patients: a Comparison Between TDF Monotherapy and TDF-based Combination Therapy

• Sponsor: Yonsei University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02019966
• Collaborator: (none)
• Enrollment: 1,020
• Location: 1
• Actual Duration (Months): 38.8
• Patients Per Site Per Month: 26.3

Study Details

Study Description

Brief Summary

Antiviral resistance remains an important issue for long-term NA therapy. For lamivudine (LAM), the rtM204V/I and rtL180M mutations occur in more than 70% after 5 years of therapy. In Korea, primarily owing to limited subsidization policy in the health insurance system, many patients with LMV-resistance had been treated with either rescue ADV or ETV 1.0 mg monotherapy, ultimately leading to the higher prevalence of MDR strain. For those patients, rescue therapies of combining ADV with either ETV or LAM had been tried, but frequently with suboptimal responses. Rescue TDF monotherapy or TDF-based combination therapy are available in Korea for patients who had "difficult-to-treat" antiviral resistance owing to prior treatment failures. However, which is the better has not been evaluated yet. A long-term efficacy and safety of TDF-based rescue therapies in real practice for those patients should be necessary to revise the Korean guideline for the treatment of chronic hepatitis B in near future.

Condition or Disease	Intervention/Treatment	Phase
The Difficult-to-treat Chronic Hepatitis B

Study Design

• Study Type: Observational
• Actual Enrollment: 1020 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Actual Study Start Date: May 12, 2014
• Actual Primary Completion Date: Aug 4, 2017
• Actual Study Completion Date: Aug 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
TDF monotherapy TDF monotherapy - treated by tenofovir alone patients with CHB receiving rescue TDF (300mg once daily) monotherapy
TDF-based combination therapy TDF-based combination therapy - treated by tenofovir based combination therapy. patients with CHB receiving rescue TDF-based combination therapy (TDF 300mg once daily with any other nucleoside analogue such as lamivudine 100mg, telbivudine 600mg, or entecavir 1.0 mg once daily).

Outcome Measures

Primary Outcome Measures

1. The proportion of subjects who achieve a sustained HBV DNA < 60 IU/mL (Undetectable serum HBV DNA by PCR method) at each year during the on treatment follow-up period. [1, 2, and 3 years after the treatment initiation.]

   The viral response which is defined as serum HBV DNA < 60 IU/mL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• more than 20 years old adults

• chronic hepatitis B

• the patients treated by tenofovir alone or tenofovir based combination therapy because of the previous treatment failure

• the patients who agree and singed on the consent form

Exclusion Criteria:

• co-infected patients with HCV, HDV or HIV

• pregnancy or breast feeding woman or female patients who are planning to be pregnant

• past history with hepatocellular carcinoma

• combined with other liver disease including wilson, alcoholic, NASH, alpha-1 antitrypsin deficiency liver disease.

• patients with hypersensitivity for drugs

• patients who were enrolled in other clinical study within 60 days

• patients who were eligible for the clinical study according to the investor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Internal Medicine, Yonsei University College of Medicine	Seoul		Korea, Republic of	120-752

Sponsors and Collaborators

• Yonsei University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Berg T, Marcellin P, Zoulim F, Moller B, Trinh H, Chan S, Suarez E, Lavocat F, Snow-Lampart A, Frederick D, Sorbel J, Borroto-Esoda K, Oldach D, Rousseau F. Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection. Gastroenterology. 2010 Oct;139(4):1207-17. doi: 10.1053/j.gastro.2010.06.053. Epub 2010 Jun 20.
• Lim YS, Lee TH, Heo NY, Shim JH, Lee HC, Suh DJ. Entecavir plus adefovir combination treatment for chronic hepatitis B patients after failure of nucleoside/nucleotide analogues. Antivir Ther. 2012;17(1):53-60. doi: 10.3851/IMP1914.
• Tan J, Degertekin B, Wong SN, Husain M, Oberhelman K, Lok AS. Tenofovir monotherapy is effective in hepatitis B patients with antiviral treatment failure to adefovir in the absence of adefovir-resistant mutations. J Hepatol. 2008 Mar;48(3):391-8. doi: 10.1016/j.jhep.2007.09.020. Epub 2008 Jan 3.
• van Bömmel F, de Man RA, Wedemeyer H, Deterding K, Petersen J, Buggisch P, Erhardt A, Hüppe D, Stein K, Trojan J, Sarrazin C, Böcher WO, Spengler U, Wasmuth HE, Reinders JG, Möller B, Rhode P, Feucht HH, Wiedenmann B, Berg T. Long-term efficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside/nucleotide analogues. Hepatology. 2010 Jan;51(1):73-80. doi: 10.1002/hep.23246.

• Responsible Party: Yonsei University
• ClinicalTrials.gov Identifier: NCT02019966
• Other Study ID Numbers: 4-2013-0704
• First Posted: Dec 24, 2013
• Last Update Posted: Jul 17, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Hepatitis B; Hepatitis B, Chronic

Study Results

No Results Posted as of Jul 17, 2018