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

Status

UNKNOWN

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03597633

Enrollment

236

Registered

2018-07-24

Start date

2013-06-01

Completion date

2019-12-31

Last updated

2018-07-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis b With Multidrug Resistance

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

19 Years to No maximum

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Virologic Response	60 months	undetectable HBV DNA (\<20 IU/mL)
mean HBV DNA	36 months, 60 months	mean HBV DNA levels
ALT normalization	36 months, 60 months	rates of ALT normalization
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.
Genotypic resistance	36 months, 60 months	Detection of previously known mutations to be resistant to the drugs being administered.
Hepatitis B e antigen (HBeAg) seroconversion	36 months, 60 months	rates of Hepatitis B e antigen (HBeAg) seroconversion

Other

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

Countries

South Korea

Outcome results