Study Comparing Tenofovir Disoproxil Fumarate (TDF), Emtricitabine (FTC)/TDF, and Entecavir (ETV) in the Treatment of Chronic HBV in Subjects With Decompensated Liver Disease.

NCT ID: NCT00298363

Last Updated: 2013-04-25

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Study Completion Date

2011-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Chronic Hepatitis B

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Tenofovir DF

TDF 300 mg + FTC/TDF placebo + ETV placebo once daily (QD)

Group Type EXPERIMENTAL

Tenofovir disoproxil fumarate (tenofovir DF; TDF)

Intervention Type DRUG

300-mg tablet QD

FTC/TDF placebo

Intervention Type DRUG

Placebo to match FTC/TDF QD

ETV placebo

Intervention Type DRUG

Placebo to match ETV QD

FTC/TDF

FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo QD

Group Type EXPERIMENTAL

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)

Intervention Type DRUG

FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet QD

TDF placebo

Intervention Type DRUG

Placebo to match TDF QD

ETV placebo

Intervention Type DRUG

Placebo to match ETV QD

Entecavir

ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo QD

Group Type EXPERIMENTAL

Entecavir (ETV)

Intervention Type DRUG

0.5-mg or 1-mg tablet QD

TDF placebo

Intervention Type DRUG

Placebo to match TDF QD

FTC/TDF placebo

Intervention Type DRUG

Placebo to match FTC/TDF QD

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Tenofovir disoproxil fumarate (tenofovir DF; TDF)

300-mg tablet QD

Intervention Type DRUG

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)

FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet QD

Intervention Type DRUG

Entecavir (ETV)

0.5-mg or 1-mg tablet QD

Intervention Type DRUG

TDF placebo

Placebo to match TDF QD

Intervention Type DRUG

FTC/TDF placebo

Placebo to match FTC/TDF QD

Intervention Type DRUG

ETV placebo

Placebo to match ETV QD

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Viread Truvada Baraclude

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Chronic Hepatitis B infection
* 18 through 69 years of age, inclusive
* HBV DNA ≥ 1000 copies/mL
* Decompensated liver disease with all of the following:

* CPT score of 7-12 (inclusive) OR history of CPT score ≥ 7 and any CPT at screen ≤ 12
* Serum alanine aminotransferase (ALT) \< 10 x the upper limit of the normal range (ULN)
* Hemoglobin ≥ 7.5 g/dL
* Total white blood cell (WBC) count ≥ 1,500/mm\^3
* Platelet count ≥ 30,000/mm\^3
* Alpha-fetoprotein ≤ 20 ng/mL and ultrasound or other imaging with no evidence of hepatocellular carcinoma (HCC), or alpha-fetoprotein of 21-50 ng/mL and computed tomography (CT)/magnetic resonance imaging (MRI) scan with no evidence of HCC, within 6 months of screening
* Calculated creatinine clearance ≥ 50 mL/min
* Negative human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis D virus (HDV) serologies
* Less than 24 months of total prior adefovir dipivoxil exposure
* Willing and able to provide written informed consent

Exclusion Criteria

* Pregnant women, women who were breastfeeding or who believed they may have wished to become pregnant during the course of the study
* Males and females of reproductive potential who were unwilling to use an effective method of contraception during the study
* Prior use of TDF or ETV
* History of variceal bleeding, hepatorenal syndrome, Grade 3 or 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 60 days of screening
* Grade 2 hepatic encephalopathy at screening
* History of solid organ or bone marrow transplant
* Current use of hepatotoxic drugs, nephrotoxic drugs, or drugs that interfere with renal tubular secretion
* Current therapy with immunomodulators (eg, corticosteroids, interleukin-2, etc.) or investigational drugs
* Diagnosis of proximal tubulopathy
* Use of investigational agent within 30 days prior to screening
* Known hypersensitivity to TDF, FTC, ETV, or formulation excipients of any of the study drug products
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

John Flaherty, PharmD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Pfleger Liver Institute

Los Angeles, California, United States

Site Status

California Pacific Medical Center Research Institute

San Francisco, California, United States

Site Status

University of Miami, Center for Liver Diseases

Miami, Florida, United States

Site Status

Rush Presbyterian - St. Luke's Medical Center

Chicago, Illinois, United States

Site Status

Henry Ford Hospital and Health System

Detroit, Michigan, United States

Site Status

Mt. Sinai School of Medicine/ Mt. Sinai Medical Center

New York, New York, United States

Site Status

Columbia Presbyterian Medical Center

New York, New York, United States

Site Status

Metropolitan Research

Fairfax, Virginia, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Heritage Medical Research Clinic

Calgary, Alberta, Canada

Site Status

Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status

The Gordon & Leslie Diamond Centre

Vancouver, British Columbia, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Hopital Conception

Marseille, , France

Site Status

Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie

Berlin, , Germany

Site Status

Universitat Heidelberg

Heidelberg, , Germany

Site Status

Johannes Gutenberg-Universitat

Mainz, , Germany

Site Status

General Hospital of Athens "Ippokratio"

Athens, , Greece

Site Status

Universita de Padova

Padua, , Italy

Site Status

Policlinico Universitario

Udine, , Italy

Site Status

Wojewodzki Szpital Specjalistyczny im Dluskeigo

Bialystok, , Poland

Site Status

Wojewodzki Szpital Obserwacy

Bydgoszcz, , Poland

Site Status

Wojewodzki Szpital Zakazny

Warsaw, , Poland

Site Status

National University Hospital Dept. of Gastroenterology & Hepatology

Singapore, , Singapore

Site Status

Singapore General Hospital

Singapore, , Singapore

Site Status

Tan Tock Seng Hospital

Singapore, , Singapore

Site Status

Changi General Hospital

Singapore, , Singapore

Site Status

Hospital General Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clinic i Provincial de Barcelona (HCPB)

Barcelona, , Spain

Site Status

Hospital Universitario de Bellvitge

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

Hospital Universitario y Politecnico la Fe

Valencia, , Spain

Site Status

Chang Gung Memorial Hospital - Kaohsiung

Kaoshiung Hsien, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

Cathay General Hospital

Taipei, , Taiwan

Site Status

Chang-Gung Memorial Hospital

Taipei, , Taiwan

Site Status

Marmara Universitesi School of Medicine

Istanbul, , Turkey (Türkiye)

Site Status

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, , Turkey (Türkiye)

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Canada France Germany Greece Italy Poland Singapore Spain Taiwan Turkey (Türkiye)

References

Explore related publications, articles, or registry entries linked to this study.

Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, Suet-Hing Wong F, Chang TT, Horban A, Wang C, Kwan P, Buti M, Prieto M, Berg T, Kitrinos K, Peschell K, Mondou E, Frederick D, Rousseau F, Schiff ER. Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease. Hepatology. 2011 Jan;53(1):62-72. doi: 10.1002/hep.23952. Epub 2010 Oct 27.

Reference Type RESULT
PMID: 21254162 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

GS-US-174-0108

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.