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Report for Clinical Trial NCT01639092

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Multicenter Randomized Controlled Open-label Trial of Tenofovir vs. Tenofovir Plus Entecavir in Chronic Hepatitis B Patients With Genotypic Resistance to Entecavir and Partial Virologic Response to Ongoing Treatment

With the availability of potent nucloes(t)ide analogues (NA), such as tenofovir disoproxil fumarate (TDF) and entecavir (ETV), suppression of serum HBV DNA to undetectable levels by polymerase chain reaction (PCR) assays became achievable in most NA treatment-naïve patients. Until recently, however, many patients commenced antiviral treatment with inferior NAs prior to the availability of TDF or ETV, such as lamivudine (LAM) which has a low genetic barrier to resistance. ETV resistance increase up to 51% of patients after 5 years of ETV treatment in lamivudine-refractory patients. Resistance to ETV appears to occur through a two-hit mechanism with initial selection of M204V/I mutation followed by amino acid substitutions at rtT184, rtS202, or rtM250. In vitro studies showed that ETV-resistant mutations are susceptible to TDF, but there are little clinical data on the efficacy of TDF monotherapy in patients with ETV-resistance. On the other hand, there was a retrospective cohort study reporting that, with the combination of TDF and ETV, most of patients became HBV DNA undetectable after median 6 months of treatment. Probability of reaching complete HBV DNA suppression was not decreased in patients with ADV or ETV-resistance. Thus, there is no consistent treatment recommendation for patients with ETV-resistance. In this clinical trial, the investigators will clarify whether tenofovir monotherapy is as effective as tenofovir plus entecavir in inducing complete virologic response in CHB patients with genotypic resistance to ETV and partial virologic response to ongoing treatment.

NCT01639092 Chronic Viral Hepatitis B Without Delta-agent
MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis
HPO:Hepatitis

3 Interventions

Name: Tenofovir

Description: Tenofovir 300mg Daily Oral
Type: Drug
Group Labels: 1

Tenofovir monotherapy

Name: Tenofovir

Description: Tenofovir 300mg Daily Oral
Type: Drug
Group Labels: 1

Tenofovir plus Entecavir combination

Name: Entecavir

Description: Entecavir 1 mg daily Oral
Type: Drug
Group Labels: 1

Tenofovir plus Entecavir combination


Primary Outcomes

Description: The proportion of patients who achieve complete virologic response (serum HBV DNA concentrations below 15 IU/mL)

Measure: Proportion of patients with complete virologic response

Time: at week 48 of treatment

Secondary Outcomes

Description: Changes in serum HBV DNA levels during 48 weeks of treatment

Measure: Changes in serum HBV DNA levels

Time: at week 48, 96, 144, and 240 of treatment

Measure: Proportion of patients with normal ALT

Time: at week 48, 96, 144, and 240 of treatment

Measure: Proportion of patients with HBe-Ag loss or seroconversion

Time: at week 48, 96, 144, and 240 of treatment

Description: The proportion of patients with resistance mutations to Entecavir or Tenofovir at week 48

Measure: Proportion of patients with resistance mutations to Entecavir or Tenofovir

Time: at week 48, 96, 144, and 240 of treatment

Description: Virologic breakthrough is defined as the increase in serum HBV DNA by >1 log10 (10-fold) above nadir after achieving virologic response as determined by at least 2 consecutive measurements of at least 2 weeks apart, during continued treatment

Measure: Proportion of patients with virologic breakthrough

Time: at week 48, 96, 144, and 240 of treatment

Description: The proportion of patients who achieve complete virologic response (serum HBV DNA concentrations below 15 IU/mL)

Measure: Proportion of patients with complete virologic response

Time: at week 48, 96, 144, and 240 of treatment

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 M204V

Resistance to ETV appears to occur through a two-hit mechanism with initial selection of M204V/I mutation followed by amino acid substitutions at rtT184, rtS202, or rtM250. --- M204V ---



HPO Nodes


HPO: