Conditions: Chronic Hepatitis B
Keywords: Hepatitis; Hepatitis B virus; Tenofovir
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 112
Healthy volunteers: no

Brief summary:
This study was designed to evaluate and compare the safety and tolerability of tenofovir disoproxil fumarate (TDF), emtricitabine (FTC)/TDF, and entecavir (ETV) in the treatment of hepatitis B patients with decompensated liver disease. Safety was assessed by evaluating adverse events (AEs) and laboratory abnormalities. Efficacy was assessed by evaluating reductions in Child-Pugh-Turcotte (CPT) and Model for End Stage Liver Disease (MELD) scores, reductions in hepatitis B virus (HBV) deoxyribonucleic acid (DNA), changes in liver enzymes, development of drug-resistant mutations, and generation of antibody to virus.

A maximum randomized treatment duration of 168 weeks was planned. Since subjects with decompensated liver disease were enrolled into this study, it was necessary to provide early intervention strategies if profound viral suppression was not expeditiously achieved. For this reason, subjects with a decrease in plasma HBV DNA from baseline of \< 2 log\_10 copies/mL and plasma HBV DNA \> 10,000 copies/mL (or plasma HBV DNA \> 1,000 copies/mL for subjects who entered the study with HBV DNA \< 10,000 copies/mL) at Week 8 had the option to start open-label FTC/TDF and continue in the study. Subjects with a virologic breakthrough or who had plasma HBV DNA levels remaining \> 400 copies/mL (confirmed) at or after 24 weeks of treatment could have been unblinded at the investigator's discretion for selection of alternative anti-HBV therapy that may have included open-label FTC/TDF. If study drug was permanently discontinued, immediate initiation of another anti-HBV regimen was strongly recommended.

Detailed description:

Arms:
arm 1: TDF 300 mg + FTC/TDF placebo + ETV placebo once daily (QD) arm 2: FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo QD arm 3: ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo QD

Interventions: intervention 1: Tenofovir disoproxil fumarate (tenofovir DF; TDF) intervention 2: Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) intervention 3: Entecavir (ETV) intervention 4: TDF placebo intervention 5: FTC/TDF placebo intervention 6: ETV placebo
Intervention descriptions: intervention 1: 300-mg tablet QD intervention 2: FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet QD intervention 3: 0.5-mg or 1-mg tablet QD intervention 4: Placebo to match TDF QD intervention 5: Placebo to match FTC/TDF QD intervention 6: Placebo to match ETV QD

Protocol document: