A Randomized Controlled Trial on the Efficacy of Tenofovir Disoproxil Fumarate (TDF)-Switch Therapy in Chronic Hepatitis B Patients With Incomplete Response to Entecavir

NCT01918631 | Completed DMC

• 1 other identifier: TDF-ETV-RCT studyA
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Currently, five nucleos(t)ide analogs are approved for the treatment of chronic hepatitis B, namely lamivudine, adefovir dipivoxil, telbivudine, entecavir (ETV) and tenofovir disoproxil fumarate (TDF). ETV and TDF are recommended as first-line therapy by all regional guidelines due to their high anti-viral potency and low risk of inducing resistance. ETV monotherapy for chronic HBV infection is highly effective in both HBeAg-positive and negative treatment-naïve patients. The cumulative probability of maintained virologic suppression with undetectable HBV DNA at year 1, 2 and 3 were 76.5%, 83.0% and 88.3% respectively. TDF is another potent anti-viral treatment for chronic hepatitis B. Up to 72% and 87% of HBeAg-positive and -negative patients achieved undetectable HBV DNA by week 144 of TDF monotherapy. It is also effective in patients with prior exposure to other nucleo(s)tide analogs. Previous studies demonstrated that TDF can be used as an effective rescue therapy in lamivudine or adefovir-treated patients with incomplete virologic response. However, the optimal treatment for patients with suboptimal response to ETV is uncertain. With this background, we will conduct a randomized controlled trial to evaluate the efficacy of TDF switch therapy in patients with incomplete virologic response to ETV treatment.

Conditions

Chronic Heptitis B

Outcome Measures

Primary Outcomes (1)

• Maintained virologic response

  Undetectable HBV DNA by PCR assay

  48 weeks

Secondary Outcomes (4)

• Undetectable HBV DNA at week 24 and 48

  At week 24 and 48

• Amino acid substitutions or drug resistance

  At week 48

• Normal ALT, RFT and bone profile

  At week 24 and 48

• Numbers of adverse events or serious adverse events

  At week 48

Study Arms (2)

Entecavir

ACTIVE COMPARATOR

Entecavir 0.5mg QD for 48 weeks

Drug: Entecavir

tenofovir disoproxil fumarate

ACTIVE COMPARATOR

tenofovir disoproxil fumarate 300mg QD for 48 weeks

Drug: tenofovir disoproxil fumarate

Interventions

tenofovir disoproxil fumarate DRUG

tenofovir disoproxil fumarate

Entecavir DRUG

Entecavir

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or above
• Positive hepatitis B surface antigen for at least 6 months
• On ETV monotherapy as anti-viral treatment for at least 52 weeks
• HBV DNA (\>20 IU/ml) at week 52 or more of ETV treatment
• Written informed consent obtained

You may not qualify if:

• Concurrent use of other antiviral treatment (including oral nucleos(t)ide analogs, interferon or pegylated interferon) for chronic hepatitis B.
• Concurrent use of steroids or immunosuppressive agents more than two week consecutively
• Co-infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
• Features suggestive of concomitant chronic liver diseases: positive anti-nuclear antibody (ANA) titer above 1/160, positive anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA), abnormal serum ceruloplasmin or iron profile, or histological features of alternative chronic liver disease
• Pregnancy or breast feeding.
• Inability or unwillingness to give informed consent or abide by the requirements of the study.
• History of other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
• Patients with baseline significant impaired renal function with creatinine clearance \<30 ml/min or receiving dialysis for end stage renal disease.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Related Publications (18)

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MeSH Terms

Interventions

Tenofovir; entecavir

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Grace LH Wong, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 6, 2013
• First Posted: August 8, 2013
• Study Start: August 1, 2013
• Primary Completion: January 1, 2017
• Study Completion: January 31, 2017
• Last Updated: July 19, 2017

Record last verified: 2017-07

Locations

HK (1)