Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00117676
Registration number
NCT00117676
Ethics application status
Date submitted
30/06/2005
Date registered
8/07/2005
Date last updated
7/03/2017
Titles & IDs
Public title
A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Negative Chronic Hepatitis B
Query!
Scientific title
A Randomized, Double-Blind, Controlled Evaluation of Tenofovir DF Versus Adefovir Dipivoxil for the Treatment of Presumed Pre-Core Mutant Chronic Hepatitis B
Query!
Secondary ID [1]
0
0
2004-005119-27
Query!
Secondary ID [2]
0
0
GS-US-174-0102
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B
0
0
Query!
Condition category
Condition code
Infection
0
0
0
0
Query!
Other infectious diseases
Query!
Oral and Gastrointestinal
0
0
0
0
Query!
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - TDF
Treatment: Drugs - ADV
Treatment: Drugs - TDF placebo
Treatment: Drugs - ADV placebo
Treatment: Drugs - FTC/TDF
Experimental: TDF-TDF - TDF plus ADV placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC tablet) to their treatment regimen in the open-label period.
Active comparator: ADV-TDF - ADV plus TDF placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of FTC/TDF FDC tablet) to their treatment regimen in the open-label period.
Treatment: Drugs: TDF
300 mg tablet administered orally once daily
Treatment: Drugs: ADV
10 mg tablet administered orally once daily
Treatment: Drugs: TDF placebo
Tablet administered orally once daily
Treatment: Drugs: ADV placebo
Tablet administered orally once daily
Treatment: Drugs: FTC/TDF
200/300 mg fixed-dose combination (FDC) tablet administered orally once daily
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48
Query!
Assessment method [1]
0
0
Complete response was a composite endpoint defined as histological response and HBV DNA \< 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.
A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40.
Query!
Timepoint [1]
0
0
Baseline; Week 48
Query!
Secondary outcome [1]
0
0
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
Week 48
Query!
Secondary outcome [2]
0
0
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96
Query!
Assessment method [2]
0
0
Query!
Timepoint [2]
0
0
Week 96
Query!
Secondary outcome [3]
0
0
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
Weeks 144, 192, 240, 288, 336, and 384
Query!
Secondary outcome [4]
0
0
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
Weeks 432 and 480
Query!
Secondary outcome [5]
0
0
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Assessment method [5]
0
0
Query!
Timepoint [5]
0
0
Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Secondary outcome [6]
0
0
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Assessment method [6]
0
0
Query!
Timepoint [6]
0
0
Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Secondary outcome [7]
0
0
Percentage of Participants With Histological Response at Week 48
Query!
Assessment method [7]
0
0
Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.
Query!
Timepoint [7]
0
0
Baseline; Week 48
Query!
Secondary outcome [8]
0
0
Percentage of Participants With Histological Response at Week 240
Query!
Assessment method [8]
0
0
Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.
Query!
Timepoint [8]
0
0
Baseline; Week 240
Query!
Secondary outcome [9]
0
0
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48
Query!
Assessment method [9]
0
0
The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).
Query!
Timepoint [9]
0
0
Baseline; Week 48
Query!
Secondary outcome [10]
0
0
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240
Query!
Assessment method [10]
0
0
The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).
Query!
Timepoint [10]
0
0
Baseline; Week 240
Query!
Secondary outcome [11]
0
0
Ranked Assessment of Necroinflammation and Fibrosis at Week 48
Query!
Assessment method [11]
0
0
Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.
Query!
Timepoint [11]
0
0
Baseline; Week 48
Query!
Secondary outcome [12]
0
0
Ranked Assessment of Necroinflammation and Fibrosis at Week 240
Query!
Assessment method [12]
0
0
Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.
Query!
Timepoint [12]
0
0
Baseline; Week 240
Query!
Secondary outcome [13]
0
0
Percentage of Participants With ALT Normalization at Week 48
Query!
Assessment method [13]
0
0
ALT normalization was defined as ALT \> upper limit of normal (ULN) at baseline and within the normal range at the end of blinded treatment. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged = 69.
Query!
Timepoint [13]
0
0
Baseline; Week 48
Query!
Secondary outcome [14]
0
0
Percentage of Participants With ALT Normalization at Weeks 96
Query!
Assessment method [14]
0
0
ALT normalization was defined as ALT \> ULN at baseline and within the normal range at Week 96. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged = 69.
Query!
Timepoint [14]
0
0
Baseline; Week 96
Query!
Secondary outcome [15]
0
0
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384
Query!
Assessment method [15]
0
0
ALT normalization was defined as ALT \> ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged = 69.
Query!
Timepoint [15]
0
0
Baseline; Weeks 144, 192, 240, 288, 336, and 384
Query!
Secondary outcome [16]
0
0
Percentage of Participants With ALT Normalization at Weeks 432 and 480
Query!
Assessment method [16]
0
0
ALT normalization was defined as ALT \> ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged = 69.
Query!
Timepoint [16]
0
0
Baseline; Weeks 432 and 480
Query!
Secondary outcome [17]
0
0
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Assessment method [17]
0
0
Query!
Timepoint [17]
0
0
Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Secondary outcome [18]
0
0
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Assessment method [18]
0
0
Query!
Timepoint [18]
0
0
Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Secondary outcome [19]
0
0
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48
Query!
Assessment method [19]
0
0
HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 48. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 48.
Query!
Timepoint [19]
0
0
Baseline; Week 48
Query!
Secondary outcome [20]
0
0
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96
Query!
Assessment method [20]
0
0
HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 96. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 96.
Query!
Timepoint [20]
0
0
Baseline; Week 96
Query!
Secondary outcome [21]
0
0
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Assessment method [21]
0
0
HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.
Query!
Timepoint [21]
0
0
Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480
Query!
Secondary outcome [22]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)
Query!
Assessment method [22]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 48, those with viral breakthrough, and those who discontinued after Week 24 with HBV DNA = 400 copies/mL.
Query!
Timepoint [22]
0
0
Baseline; Week 48
Query!
Secondary outcome [23]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)
Query!
Assessment method [23]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 96 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 48 with HBV DNA = 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen and had HBV DNA = 400 copies/mL at the time of the addition.
Query!
Timepoint [23]
0
0
Baseline; Weeks 49 to 96
Query!
Secondary outcome [24]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)
Query!
Assessment method [24]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 144 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 96 with HBV DNA = 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 96 and had HBV DNA = 400 copies/mL at the time of the addition.
Query!
Timepoint [24]
0
0
Baseline; Weeks 97 to 144
Query!
Secondary outcome [25]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)
Query!
Assessment method [25]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 192 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 144 with HBV DNA = 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 144 and had HBV DNA = 400 copies/mL at the time of the addition.
Query!
Timepoint [25]
0
0
Baseline; Weeks 145 to 192
Query!
Secondary outcome [26]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)
Query!
Assessment method [26]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 240 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 192 with HBV DNA = 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 192 and had HBV DNA = 400 copies/mL at the time of the addition.
Query!
Timepoint [26]
0
0
Baseline; Weeks 193 to 240
Query!
Secondary outcome [27]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)
Query!
Assessment method [27]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 288 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 240 with HBV DNA = 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 240 and had HBV DNA = 400 copies/mL at the time of the addition.
Query!
Timepoint [27]
0
0
Baseline; Weeks 241 to 288
Query!
Secondary outcome [28]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)
Query!
Assessment method [28]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 336 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 288 with HBV DNA = 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 288 and had HBV DNA = 400 copies/mL at the time of the addition.
Query!
Timepoint [28]
0
0
Baseline; Weeks 289 to 336
Query!
Secondary outcome [29]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)
Query!
Assessment method [29]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 384 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 336 with HBV DNA = 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 336 and had HBV DNA = 400 copies/mL at the time of the addition.
Query!
Timepoint [29]
0
0
Baseline; Weeks 337 to 384
Query!
Secondary outcome [30]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)
Query!
Assessment method [30]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 432 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 384 with HBV DNA = 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 384 and had HBV DNA = 400 copies/mL at the time of the addition.
Query!
Timepoint [30]
0
0
Baseline; Weeks 385 to 432
Query!
Secondary outcome [31]
0
0
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)
Query!
Assessment method [31]
0
0
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA = 400 copies/mL at Week 480 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 432 with HBV DNA = 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 432 and had HBV DNA = 400 copies/mL at the time of the addition.
Query!
Timepoint [31]
0
0
Baseline; Weeks 433 to 480
Query!
Eligibility
Key inclusion criteria
Key
* Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for at least 6 months.
* 18 through 69 years of age, inclusive.
* Active hepatitis B e-antigen (HBeAg) negative chronic HBV infection, with all of the following:
* HBeAg negative and HBeAb positive at screening
* Alanine aminotransferase (ALT) levels > the upper limit of the normal range (ULN) and = 10 x ULN
* Serum HBV DNA > 100,000 copies/mL at screening
* Creatinine clearance = 70 mL/min
* Hemoglobin = 8 g/dL
* Neutrophils = 1,000 /mL
* Knodell necroinflammatory score = 3 and a Knodell fibrosis score < 4; however, up to 120 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible for enrollment
* Negative serum ß-human chorionic gonadotropin (hCG)
* Nucleotide naive, ie, no prior nucleotide (TDF or ADV) therapy for greater than 12 weeks
* Nucleoside naive, ie, no prior nucleoside (any nucleoside) therapy for greater than 12 weeks. However, up to 120 patients with > 12 weeks prior lamivudine experience will be eligible
* Willing and able to provide written informed consent
* Had a liver biopsy performed within 6 months of baseline and has readable biopsy slides or agrees to have a biopsy performed prior to baseline
Key
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
69
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Pregnant women, women who are breast feeding, or women who believe they may wish to become pregnant during the course of the study
* Males and females of reproductive potential who are unwilling to use an effective method of contraception during the study.
* Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin time (PT) > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage)
* Received any nucleoside, nucleotide (TDF or ADV) or interferon (pegylated or not) therapy within 6 months prior to the pre treatment biopsy
* Evidence of hepatocellular carcinoma (HCC)
* Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV)
* Significant renal, cardiovascular, pulmonary, or neurological disease
* Received solid organ or bone marrow transplantation
* Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
* Has proximal tubulopathy
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/02/2005
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/01/2016
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
382
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Query!
Recruitment hospital [1]
0
0
- Camperdown
Query!
Recruitment hospital [2]
0
0
- Concord
Query!
Recruitment hospital [3]
0
0
- Westmead
Query!
Recruitment hospital [4]
0
0
- Woolloongabba
Query!
Recruitment hospital [5]
0
0
- Clayton
Query!
Recruitment hospital [6]
0
0
- Fitzroy
Query!
Recruitment hospital [7]
0
0
- Heidelberg
Query!
Recruitment hospital [8]
0
0
- Prahan
Query!
Recruitment postcode(s) [1]
0
0
2050 - Camperdown
Query!
Recruitment postcode(s) [2]
0
0
2139 - Concord
Query!
Recruitment postcode(s) [3]
0
0
2145 - Westmead
Query!
Recruitment postcode(s) [4]
0
0
40102 - Woolloongabba
Query!
Recruitment postcode(s) [5]
0
0
3168 - Clayton
Query!
Recruitment postcode(s) [6]
0
0
3065 - Fitzroy
Query!
Recruitment postcode(s) [7]
0
0
3084 - Heidelberg
Query!
Recruitment postcode(s) [8]
0
0
3004 - Prahan
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Georgia
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Hawaii
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Massachusetts
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Michigan
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Missouri
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
New York
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Virginia
Query!
Country [9]
0
0
Bulgaria
Query!
State/province [9]
0
0
Sofia
Query!
Country [10]
0
0
Bulgaria
Query!
State/province [10]
0
0
Varna
Query!
Country [11]
0
0
Canada
Query!
State/province [11]
0
0
Alberta
Query!
Country [12]
0
0
Canada
Query!
State/province [12]
0
0
British Columbia
Query!
Country [13]
0
0
Canada
Query!
State/province [13]
0
0
Manitoba
Query!
Country [14]
0
0
Canada
Query!
State/province [14]
0
0
Ontario
Query!
Country [15]
0
0
Czech Republic
Query!
State/province [15]
0
0
Brno
Query!
Country [16]
0
0
Czech Republic
Query!
State/province [16]
0
0
Hradec Kralove
Query!
Country [17]
0
0
Czech Republic
Query!
State/province [17]
0
0
Praha 4
Query!
Country [18]
0
0
Czech Republic
Query!
State/province [18]
0
0
Praha 6 - Stresovice
Query!
Country [19]
0
0
France
Query!
State/province [19]
0
0
Clichy
Query!
Country [20]
0
0
France
Query!
State/province [20]
0
0
Creteil
Query!
Country [21]
0
0
France
Query!
State/province [21]
0
0
Lille
Query!
Country [22]
0
0
France
Query!
State/province [22]
0
0
Lyon
Query!
Country [23]
0
0
France
Query!
State/province [23]
0
0
Nancy
Query!
Country [24]
0
0
France
Query!
State/province [24]
0
0
Paris
Query!
Country [25]
0
0
France
Query!
State/province [25]
0
0
Strasbourg
Query!
Country [26]
0
0
France
Query!
State/province [26]
0
0
Toulouse
Query!
Country [27]
0
0
Germany
Query!
State/province [27]
0
0
Duesseldorf
Query!
Country [28]
0
0
Germany
Query!
State/province [28]
0
0
Frankfurt
Query!
Country [29]
0
0
Germany
Query!
State/province [29]
0
0
Hamburg
Query!
Country [30]
0
0
Germany
Query!
State/province [30]
0
0
Hannover
Query!
Country [31]
0
0
Germany
Query!
State/province [31]
0
0
Herne
Query!
Country [32]
0
0
Germany
Query!
State/province [32]
0
0
Homburg/Saar
Query!
Country [33]
0
0
Germany
Query!
State/province [33]
0
0
Mainz
Query!
Country [34]
0
0
Germany
Query!
State/province [34]
0
0
Munchen
Query!
Country [35]
0
0
Germany
Query!
State/province [35]
0
0
Tubingen
Query!
Country [36]
0
0
Greece
Query!
State/province [36]
0
0
Athens
Query!
Country [37]
0
0
Greece
Query!
State/province [37]
0
0
Larissa
Query!
Country [38]
0
0
Greece
Query!
State/province [38]
0
0
Leipzig
Query!
Country [39]
0
0
Greece
Query!
State/province [39]
0
0
Thessaloniki
Query!
Country [40]
0
0
Italy
Query!
State/province [40]
0
0
Bologna
Query!
Country [41]
0
0
Italy
Query!
State/province [41]
0
0
Torino
Query!
Country [42]
0
0
Netherlands
Query!
State/province [42]
0
0
Rotterdam
Query!
Country [43]
0
0
New Zealand
Query!
State/province [43]
0
0
Auckland
Query!
Country [44]
0
0
New Zealand
Query!
State/province [44]
0
0
Hamilton
Query!
Country [45]
0
0
New Zealand
Query!
State/province [45]
0
0
Whakatane
Query!
Country [46]
0
0
Poland
Query!
State/province [46]
0
0
Bialystok
Query!
Country [47]
0
0
Poland
Query!
State/province [47]
0
0
Bydgoszcz
Query!
Country [48]
0
0
Poland
Query!
State/province [48]
0
0
Chorzow
Query!
Country [49]
0
0
Poland
Query!
State/province [49]
0
0
Krakow
Query!
Country [50]
0
0
Poland
Query!
State/province [50]
0
0
Warszawa
Query!
Country [51]
0
0
Poland
Query!
State/province [51]
0
0
Wroclaw
Query!
Country [52]
0
0
Spain
Query!
State/province [52]
0
0
Madrid
Query!
Country [53]
0
0
Spain
Query!
State/province [53]
0
0
Barcelona
Query!
Country [54]
0
0
Spain
Query!
State/province [54]
0
0
Valencia
Query!
Country [55]
0
0
Turkey
Query!
State/province [55]
0
0
Bursa
Query!
Country [56]
0
0
Turkey
Query!
State/province [56]
0
0
Istanbul
Query!
Country [57]
0
0
Turkey
Query!
State/province [57]
0
0
Izmir
Query!
Country [58]
0
0
United Kingdom
Query!
State/province [58]
0
0
London
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Gilead Sciences
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
This primary objectives of this study are to compare the efficacy, safety, and tolerability of tenofovir disoproxil fumarate (TDF) versus adefovir dipivoxil (ADV) for the treatment of pre-core mutant chronic hepatitis B. Participants will receive TDF or ADV for 48 weeks (double-blind). After 48 weeks, eligible participants switched to open-label TDF for up to 480 weeks.
Query!
Trial website
https://clinicaltrials.gov/study/NCT00117676
Query!
Trial related presentations / publications
Kitrinos KM, Corsa A, Liu Y, Flaherty J, Snow-Lampart A, Marcellin P, Borroto-Esoda K, Miller MD. No detectable resistance to tenofovir disoproxil fumarate after 6 years of therapy in patients with chronic hepatitis B. Hepatology. 2014 Feb;59(2):434-42. doi: 10.1002/hep.26686. Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Aguilar Schall R, Bornstein JD, Kitrinos KM, Subramanian GM, McHutchison JG, Heathcote EJ. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013 Feb 9;381(9865):468-75. doi: 10.1016/S0140-6736(12)61425-1. Epub 2012 Dec 10. Gordon SC, Krastev Z, Horban A, Petersen J, Sperl J, Dinh P, Martins EB, Yee LJ, Flaherty JF, Kitrinos KM, Rustgi VK, Marcellin P. Efficacy of tenofovir disoproxil fumarate at 240 weeks in patients with chronic hepatitis B with high baseline viral load. Hepatology. 2013 Aug;58(2):505-13. doi: 10.1002/hep.26277. Epub 2013 May 3. Tsai NC, Marcellin P, Buti M, Washington MK, Lee SS, Chan S, Trinh H, Flaherty JF, Kitrinos KM, Dinh P, Charuworn P, Subramanian GM, Gane E. Viral suppression and cirrhosis regression with tenofovir disoproxil fumarate in Asians with chronic hepatitis B. Dig Dis Sci. 2015 Jan;60(1):260-8. doi: 10.1007/s10620-014-3336-7. Epub 2014 Sep 2. Fung S, Gordon SC, Krastev Z, Horban A, Petersen J, Sperl J, Gane E, Jacobson IM, Yee LJ, Dinh P, Martins EB, Flaherty JF, Kitrinos KM, Dusheiko G, Trinh H, Flisiak R, Rustgi VK, Buti M, Marcellin P. Tenofovir disoproxil fumarate in Asian or Pacific Islander chronic hepatitis B patients with high viral load (>/= 9 log10 copies/ml). Liver Int. 2015 Feb;35(2):422-8. doi: 10.1111/liv.12694. Epub 2014 Oct 28. Buti M, Fung S, Gane E, Afdhal NH, Flisiak R, Gurel S, Flaherty JF, Martins EB, Yee LJ, Dinh P, Bornstein JD, Mani Subramanian G, Janssen HL, George J, Marcellin P. Long-term clinical outcomes in cirrhotic chronic hepatitis B patients treated with tenofovir disoproxil fumarate for up to 5 years. Hepatol Int. 2015 Apr;9(2):243-50. doi: 10.1007/s12072-015-9614-4. Epub 2015 Mar 13. Buti M, Tsai N, Petersen J, Flisiak R, Gurel S, Krastev Z, Aguilar Schall R, Flaherty JF, Martins EB, Charuworn P, Kitrinos KM, Subramanian GM, Gane E, Marcellin P. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection. Dig Dis Sci. 2015 May;60(5):1457-64. doi: 10.1007/s10620-014-3486-7. Epub 2014 Dec 23. Corsa A, Liu Y, Flaherty JF, Marcellin P, Miller M, Kitrinos KM. No Detectable Resistance to Tenofovir Disoproxil Fumarate (TDF) in HBeAg+ and HBeAg- Patients With Chronic Hepatitis B (CHB) After Eight Years of Treatment [Abstract 1707]. The 65th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting (AASLD); 2014 08-10 November; Boston MA. Marcellin P, Gane EJ, Flisiak R, Trinh HN, Petersen J, Gurel S, et al. Long Term Treatment with Tenofovir Disoproxil Fumarate for Chronic Hepatitis B Infection is Safe and Well Tolerated and Associated with Durable Virologic Response with no Detectable Resistance: 8 Year Results from Two Phase 3 Trials [Abstract]. 55th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2014 November 7-11; Boston, MA. Gane EJ, Marcellin P, Sievert W, Trinh HN, Shiffman ML, Washington MK, et al. Five years of Treatment with Tenofovir DF for Chronic Hepatitis B Infection in Asian Patients is Associated with Sustained Viral Suppression and Significant Regression of Histological Fibrosis and Cirrhosis [Poster Number 1429]. 62nd Annual Meeting of the American Association for the Study of Liver Diseases; 2011 November 4-8; San Francisco, California. Liu Y, Corsa AC, Buti M, Cathcart AL, Flaherty JF, Miller MD, Kitrinos KM, Marcellin P, Gane EJ. No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg- patients with chronic hepatitis B after 8 years of treatment. J Viral Hepat. 2017 Jan;24(1):68-74. doi: 10.1111/jvh.12613. Epub 2016 Sep 23. Marcellin P, Wong DK, Sievert W, Buggisch P, Petersen J, Flisiak R, Manns M, Kaita K, Krastev Z, Lee SS, Cathcart AL, Crans G, Op den Brouw M, Jump B, Gaggar A, Flaherty J, Buti M. Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection. Liver Int. 2019 Oct;39(10):1868-1875. doi: 10.1111/liv.14155. Epub 2019 Jul 10. Buti M, Wong DK, Gane E, Flisiak R, Manns M, Kaita K, Janssen HLA, Op den Brouw M, Jump B, Kitrinos K, Crans G, Flaherty J, Gaggar A, Marcellin P. Safety and efficacy of stopping tenofovir disoproxil fumarate in patients with chronic hepatitis B following at least 8 years of therapy: a prespecified follow-up analysis of two randomised trials. Lancet Gastroenterol Hepatol. 2019 Apr;4(4):296-304. doi: 10.1016/S2468-1253(19)30015-9. Epub 2019 Feb 20. Jacobson IM, Washington MK, Buti M, Thompson A, Afdhal N, Flisiak R, Akarca US, Tchernev KG, Flaherty JF, Aguilar Schall R, Myers RP, Subramanian GM, McHutchison JG, Younossi Z, Marcellin P, Patel K. Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy. Clin Gastroenterol Hepatol. 2017 Jul;15(7):1087-1094.e2. doi: 10.1016/j.cgh.2017.01.032. Epub 2017 Feb 12. Pan CQ, Chan S, Trinh H, Yao A, Bae H, Lou L. Similar efficacy and safety of tenofovir in Asians and non-Asians with chronic hepatitis B. World J Gastroenterol. 2015 May 14;21(18):5524-31. doi: 10.3748/wjg.v21.i18.5524. Heathcote EJ, Marcellin P, Buti M, Gane E, De Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert F, Kurdas OO, Shiffman ML, Trinh H, Gurel S, Snow-Lampart A, Borroto-Esoda K, Mondou E, Anderson J, Sorbel J, Rousseau F. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Gastroenterology. 2011 Jan;140(1):132-43. doi: 10.1053/j.gastro.2010.10.011. Epub 2010 Oct 16. Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert F, Kurdas OO, Shiffman ML, Trinh H, Washington MK, Sorbel J, Anderson J, Snow-Lampart A, Mondou E, Quinn J, Rousseau F. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008 Dec 4;359(23):2442-55. doi: 10.1056/NEJMoa0802878.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Gilead Study Director
Query!
Address
0
0
Gilead Sciences
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Type
Citations or Other Details
Journal
Kitrinos KM, Corsa A, Liu Y, Flaherty J, Snow-Lamp...
[
More Details
]
Journal
Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, ...
[
More Details
]
Journal
Gordon SC, Krastev Z, Horban A, Petersen J, Sperl ...
[
More Details
]
Journal
Tsai NC, Marcellin P, Buti M, Washington MK, Lee S...
[
More Details
]
Journal
Fung S, Gordon SC, Krastev Z, Horban A, Petersen J...
[
More Details
]
Journal
Buti M, Fung S, Gane E, Afdhal NH, Flisiak R, Gure...
[
More Details
]
Journal
Buti M, Tsai N, Petersen J, Flisiak R, Gurel S, Kr...
[
More Details
]
Journal
Corsa A, Liu Y, Flaherty JF, Marcellin P, Miller M...
[
More Details
]
Journal
Marcellin P, Gane EJ, Flisiak R, Trinh HN, Peterse...
[
More Details
]
Journal
Gane EJ, Marcellin P, Sievert W, Trinh HN, Shiffma...
[
More Details
]
Journal
Liu Y, Corsa AC, Buti M, Cathcart AL, Flaherty JF,...
[
More Details
]
Results are available at
https://clinicaltrials.gov/study/NCT00117676
Download to PDF