Prophylactic Entecavir for HBV Reactivation in Past HBV Infected Patients With Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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This study is a randomized, prospective, comparative study of the effectiveness of prophylactic entecavir treatment for HBV reactivation in past HBV infected patients (HBsAg-, HBcIgG+) with hematopoietic stem cell transplantation.

Detailed Description
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This study is a randomized, prospective, comparative study of the effectiveness of prophylactic entecavir treatment for HBV reactivation in past HBV infected patients (HBsAg-, HBcIgG+) with hematopoietic stem cell transplantation. In this study, patients are randomized into treatment group or delayed treatment group. * Stratified randomization (Block randomization within strata) according to the presence of HBsAb at baseline was used in this study. Experimental: Treatment group (n=82) The intervention group take entecavir 0.5mg everyday by oral administration for 3 years after hematopoietic stem cell transplantation. The intervention group visit clinic every month and examined liver function test, HBsAg/Ab. HBV DNA level is examined at every 3 months. * oral administration of entecavir is planned to start within 7 days after hematopoietic stem cell transplantation. No Intervention: delayed treatment group (n=82) The delayed treatment group visit clinic every month and examined liver function test, HBsAg/Ab. HBV DNA level is examined at every 3 months. If the patient in the delayed treatment group shows HBV reactivation (positive HBsAg or HBV DNA ≥10 IU/mL), entecavir treatment is started.

Official Title
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A Randomized, Prospective, Comparative Study of the Effectiveness of Prophylactic Entecavir Treatment for HBV Reactivation in Past HBV Infected Patients With Hematopoietic Stem Cell Transplantation

Conditions
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Hepatitis B Reactivation, Hematopoietic Stem Cell Transplantation, Antiviral Drug, HBV

Intervention / Treatment
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* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 19 - 70 patients receiving hematopoietic stem cell transplantation HBV serologic test: HBsAg (-), anti-HBc IgG (+) ECOG performence: 0-2 patients with informed consent Exclusion Criteria: HBV DNA (+, ≥10 IU/mL) at the time of screening Receiving hematopoietic stem cell transplantation from donor with HBsAg+ Combined other chronic liver disease (severe alcoholics, autoimmune hepatitis, chronic hepatitis C etc.) HIV (+) Previous antiviral therapy history for chronic hepatitis B Other concomitant malignancy combined autoimmune disease (rheumatic arthritis, SLE etc) CTP class B, C Decompensated complications (ascites, hepatic encephalopathy etc.) active tuberculosis

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>The intervention group take entecavir 0.5mg everyday by oral administration for 3 years after hematopoietic stem cell transplantation. The intervention group visit clinic every month and examined liver function test, HBsAg/Ab. HBV DNA level is examined at every 3 months. | Drug: Entecavir<br>* The intervention group take entecavir 0.5mg everyday by oral administration for 3 years after hematopoietic stem cell transplantation.<br>* Other names: Prophylactic treatment group;|
| No Intervention: delayed treatment group<br>The delayed treatment group visit clinic every month and examined liver function test, HBsAg/Ab. HBV DNA level is examined at every 3 months. If the patient in the delayed treatment group shows HBV reactivation (positive HBsAg or HBV DNA ≥10 IU/mL), entecavir treatment is started. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the rate of HBV reactivation between the treatment and delayed treatment groups. | Comparing the rate of HBV reactivation between the treatment and delayed treatment groups during 3 years after hematopoietic stem cell transplantation * Definition of HBV reactivation: HBsAg ≥ 1.0 S/CO or HBV DNA ≥ 10 IU/mL | The primary outcome is evaluated during 3 years after hematopoietic stem cell transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the rate of active hepatitis with HBV reactivation between the treatment and delayed treatment groups. | Comparing the rate of active hepatitis with HBV reactivation between the treatment and delayed treatment groups. * Definition of active hepatitis: ALT >= 2 times of upper normal limit | The secondary outcomes are evaluated during 3 years after hematopoietic stem cell transplantation. | 
| Comparison of the rate of hepatic failure related to HBV reactivation between the treatment and delayed treatment groups. | Comparing the rate of hepatic failure between the treatment and delayed treatment groups. | The secondary outcomes are evaluated during 3 years after hematopoietic stem cell transplantation. | 
| Comparison of the rate of survival related to HBV reactivation between the treatment and delayed treatment groups. | Comparing the rate of survival related to HBV reactivation between the treatment and delayed treatment groups. | The secondary outcomes are evaluated during 3 years after hematopoietic stem cell transplantation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B Reactivation, hematopoietic stem cell transplantation, Prophylatic antiviral agents, Past HBV infection