Tenofovir Combination or Mono-therapy for MDR CHB

Tenofovir-based Combination Therapy or Monotherapy for Multi-drug Resistant Chronic Hepatitis B; Real World Data From Multicenter Cohort Study

Treatment of multidrug resistant (MDR) chronic hepatitis B (CHB) is still a challenging issue. Hence, the investigators will perform a multicenter prospective cohort study for the evaluation of tenofovir disoproxil fumarate (TDF)-based therapy for MDR CHB at real life settings.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis b With Multidrug Resistance

Detailed Description

Inclusion criteria were CHB patients with resistance to more than two classes of nucleos(t)ide analogues (NA) and hepatitis B virus (HBV) DNA level ≥200 IU/mL.

Patients will receive either TDF-base combination therapy or TDF monotherapy. The primary end point is virologic response (VR) defined by an undetectable HBV DNA (<20 IU/mL) at month 36.

• Study Type: Observational
• Enrollment (Actual): 236

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Ansan, Gyeonggi-do, Korea, Republic of, 15355
      • Korea University Ansan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Chronic hepatitis B patients with multiple drug resistance.

Description

Inclusion Criteria:

• CHB patients with:

  1. documented HBsAg positivity at least 6 months before enrollment
  2. age >18 years old,
  3. confirmed genotypic resistance to more than two classes of NAs
  4. HBV DNA level ≥ 200 IU/mL
  5. compensated liver diseases (defined by Child-Pugh-Turcotte score <7; prothrombin time <3 seconds above upper limit of normal or international normalized ratio <1.5; serum albumin >3 g/dL; total bilirubin <2.5 mg/dL; no history of esophago-gastric variceal bleeding, ascites, over hepatic encephalopathy)
  6. willingness to give an informed consent.

Exclusion Criteria:

1. laboratory abnormalities of low serum phosphorous level <2.0 mEq/dL, elevated serum creatinine >1.5 mg/dL, decreased creatinine clearance rate <50 mL/min, absolute neutrophil count <1000 cell/mL, or low hemoglobin level <10 g/dL (if female, <9 g/dL)
2. no definite evidence of genotypic resistance
3. positive antibody test for hepatitis C virus, hepatitis D virus, or human immunodeficiency virus
4. HCC
5. a proof of pregnant or lactating women
6. evidence of active alcohol consumption (140 g per a week for men and 70 g per a week for women)
7. any untreated malignancy.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virologic Response	undetectable HBV DNA (<20 IU/mL)	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virologic Response	undetectable HBV DNA (<20 IU/mL)	60 months
mean HBV DNA	mean HBV DNA levels	36 months, 60 months
ALT normalization	rates of ALT normalization	36 months, 60 months
Hepatitis B e antigen (HBeAg) seroconversion	rates of Hepatitis B e antigen (HBeAg) seroconversion	36 months, 60 months
virologic breakthrough	Incidence of virologic breakthrough defined by increase of HBV DNA more than 1 log IU/mL from nar dir.	36 months, 60 months
Genotypic resistance	Detection of previously known mutations to be resistant to the drugs being administered.	36 months, 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event	Any untoward event related or not related to the study medication	36 months, 60 months

Collaborators and Investigators

• Sponsor: Korea University
• Collaborators: Yonsei University; Inje University; The Catholic University of Korea; CHA University; Soon Chun Hyang University; Hallym University; Chonbuk National University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2013
• Primary Completion (Anticipated): December 31, 2018
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): July 24, 2018

Study Record Updates

• Last Update Posted (Actual): July 24, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: MDRCHB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Confidential

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No