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Comparison of Prophylactic Antiviral Efficacy in Patients Undergoing Chemotherapy: Entecavir Versus Lamivudine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sook-Hyang Jeong, Seoul National University Bundang Hospital
ClinicalTrials.gov Identifier:
NCT01580202
First received: April 4, 2012
Last updated: June 28, 2017
Last verified: June 2017
  Purpose
Patients with chronic hepatitis B who are undergoing anticancer chemotherapy are at risk of HBV reactivation and hepatitis flare. Lamivudine (LAM) prophylaxis has been recommended in such circumstance according to the practice guidelines despite of limited evidence. However, failure of LAM prophylaxis including virologic breakthrough and withdrawal hepatitis occurs occasionally, which may lead to liver-related morbidity and mortality as well as premature interruption or a delay of chemotherapy. Given relatively frequent drug resistance of LAM, studies on the proper prophylactic antiviral regimen is warranted. The present multicenter, prospective, randomized study aims to compare the effect of entecavir (ETV) versus LAM for the prevention of HBV reactivation in HBsAg-positive patients with hematologic and oncologic malignancy undergoing cytotoxic chemotherapy.

Condition Intervention Phase
Malignancy Hepatitis B Drug: Entecavir Drug: Lamivudine Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open Labeled, Multicenter Study Comparing Entecavir Versus Lamivudine as Antiviral Prophylaxis for Patients With Hepatitis B Infection Undergoing Cytotoxic Chemotherapy for Malignant Tumors

Resource links provided by NLM:


Further study details as provided by Sook-Hyang Jeong, Seoul National University Bundang Hospital:

Primary Outcome Measures:
  • The cumulative probability of HBV reactivation [ Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis ]
    10-fold or more elevation in serum HBV DNA titers above nadir


Secondary Outcome Measures:
  • Incidence of HBV-related hepatitis flare [ Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis ]
    greater than 3-fold increase of ULN (upper limit of a normal reference value) of a serum ALT level that exceeded 100 IU/L during antiviral prophylaxis and 24 week after discontinuation of antiviral prophylaxis

  • Cumulative probability of emergence of genotypic resistance [ Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis ]
    detection of mutations that have been shown in in vitro studies to confer resistance to either ETV or LAM

  • Incidence of hepatic decompensation and liver-related mortality [ Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis ]

Enrollment: 180
Study Start Date: April 2012
Study Completion Date: June 2017
Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lamivudine
LAM (100 mg/day) will be started within 1 week prior to initiation of the 1st cycle of chemotherapy, and continued until 24 weeks after completion of the last chemotherapy.
Drug: Lamivudine
lamivudine 100mg daily per os
Experimental: Entecavir
ETV (0.5 mg/day) will be started within 1 week prior to initiation of the 1st cycle of chemotherapy, and continued until 24 weeks after completion of the last chemotherapy.
Drug: Entecavir
Entecavir 0.5mg daily per os

Detailed Description:

Chronic hepatitis B virus (HBV) carriers who are undergoing anticancer chemotherapy are at risk of HBV reactivation and hepatitis flare, and lamivudine (LAM) prophylaxis is recommended according to the practice guidelines despite of limited evidence. However, failure of LAM prophylaxis defined as virologic breakthrough during LAM therapy and withdrawal hepatitis after discontinuation of LAM therapy occurs occasionally, which may lead to liver-related morbidity and mortality as well as premature interruption or a delay of chemotherapy. Considering that LAM therapy showed relatively higher rates of drug resistance and of withdrawal hepatitis, studies on the better choice of prophylactic antiviral regimen is warranted.

The purpose of our study is to conduct a multicenter, prospective, randomized study comparing the effect of entecavir (ETV) versus LAM for the prevention of HBV reactivation in HBsAg-positive patients with hematologic and oncologic malignancy undergoing cytotoxic chemotherapy.

A total one hundred eighty HBV carriers with malignancy undergoing chemotherapy will be randomly assigned to each prophylactic therapy arm of ETV and LAM group. The primary endpoint of the study is the HBV reactivation rate during antiviral therapy and 6 months after discontinuation of prophylactic antiviral therapy.

If the prophylactic efficacy of ETV is superior to that of LAM, ETV will be the preferred prophylactic therapy for HBsAg-positive cancer patients undergoing chemotherapy.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years or older
  • positive for HBsAg for at least 6 months
  • inactive or active carrier of HBV with ALT level <2xULN, chronic hepatitis and compensated cirrhosis (Child-Pugh class A)
  • malignant tumors: non-Hodgkin's lymphoma undergoing systemic chemotherapy; solid tumors undergoing chemotherapy (including adjuvant/neoadjuvant chemotherapy or concurrent chemoradiation therapy)

Exclusion Criteria:

  • positive for anti-HCV or anti-HIV antibodies
  • decompensated cirrhosis or hepatocellular carcinoma
  • expected survival of less than 1 year
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01580202

Locations
Korea, Republic of
National Cancer Center, Korea
Goyang, Gyeonggi, Korea, Republic of, 410-769
Seoul National University Bundang Hospital
Seongnam, Gyeonggi, Korea, Republic of, 463-707
Soon Chun Hyang University Bucheon Hospital
Bucheon-si, Korea, Republic of, 14584
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Seoul National University Boramae Hospital
Seoul, Korea, Republic of, 156-707
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Sook-Hyang Jeong, MD, PhD Seoul National University Bundang Hospital
  More Information

Responsible Party: Sook-Hyang Jeong, Associate Professor, Seoul National University Bundang Hospital
ClinicalTrials.gov Identifier: NCT01580202     History of Changes
Other Study ID Numbers: AI463-246
Study First Received: April 4, 2012
Last Updated: June 28, 2017

Keywords provided by Sook-Hyang Jeong, Seoul National University Bundang Hospital:
malignancy
hepatitis B
lamivudine
entecavir
prophylaxis

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Neoplasms
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Lamivudine
Entecavir
Antiviral Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-Infective Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 18, 2017