Tenofovir Combination or Mono-therapy for MDR CHB

• Conditions: Chronic Hepatitis b With Multidrug Resistance

• Registration Number: NCT03597633
• Lead Sponsor: Korea University

Brief Summary

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.

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 Timeline

• Study Start: 2013-06-01
• Status Verified: 2018-07
• Study First Submitted: 2018-07-16
• Study First Submitted QC: 2018-07-23
• Last Update Submitted: 2018-07-23
• Study First Posted: 2018-07-24
• Last Update Posted: 2018-07-24
• Primary Completion: 2018-12-31
• Study Completion: 2019-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 236

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Virologic Response	36 months	undetectable HBV DNA (\<20 IU/mL)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Korea University Ansan Hospital; 🇰🇷 Ansan, Gyeonggi-do, Korea, Republic of