Clinical trial NCT03597633: Tenofovir Combination or Mono-therapy for MDR CHB
Official title: Tenofovir-based Combination Therapy or Monotherapy for Multi-drug Resistant Chronic Hepatitis B; Real World Data From Multicenter Cohort Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis b With Multidrug Resistance
Lead sponsor: Korea University
Sponsor class: OTHER
Collaborators: name: Yonsei University
name: CHA University
name: Soon Chun Hyang University
name: Chonbuk National University
name: Hallym University
name: Inje University
name: The Catholic University of Korea
First posted: 2018-07-24
Enrollment: 236
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Chronic hepatitis B patients with multiple drug 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Virologic Response
timeFrame: 36 months
Secondary outcomes:
measure: Virologic Response
timeFrame: 60 months
measure: mean HBV DNA
timeFrame: 36 months, 60 months
measure: ALT normalization
timeFrame: 36 months, 60 months
measure: Hepatitis B e antigen (HBeAg) seroconversion
timeFrame: 36 months, 60 months
measure: virologic breakthrough
timeFrame: 36 months, 60 months
measure: Genotypic resistance
timeFrame: 36 months, 60 months
Other outcomes:
measure: Adverse event
timeFrame: 36 months, 60 months
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
Study officials:
References: