A Phase 2 interventional study of Tenofovir disoproxil fumarate (tenofovir DF; TDF) and Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in Chronic Hepatitis B, sponsored by Gilead Sciences. Completed at 38 sites in 11 countries. Open to participants aged 18 Years to 69 Years. Per ClinicalTrials.gov, last updated 2013-04-25.
Sponsored by Gilead Sciences · Phase 2, Interventional, and Treatment
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.
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This study's enrollment of 112 is above the median of 100 across 1,886 interventional studies indexed under Hepatitis A.
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A participant was required to meet all of the following inclusion criteria to be eligible for participation in the study:
Decompensated liver disease with all of the following:
Exclusion Criteria:
A participant who met any of the following exclusion criteria could not be enrolled in the study:
TDF 300 mg + FTC/TDF placebo + ETV placebo once daily (QD)
Drug: Tenofovir disoproxil fumarate (tenofovir DF; TDF) · Drug: FTC/TDF placebo · Drug: ETV placebo
FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo QD
Drug: Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) · Drug: TDF placebo · Drug: ETV placebo
ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo QD
Drug: Entecavir (ETV) · Drug: TDF placebo · Drug: FTC/TDF placebo
300-mg tablet QD
Also known as: Viread
FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet QD
Also known as: Truvada
0.5-mg or 1-mg tablet QD
Also known as: Baraclude
Placebo to match TDF QD
Placebo to match FTC/TDF QD
Placebo to match ETV QD
Percent Probability of Tolerability Failure
Tolerability failure was defined as permanent discontinuation of study drug due to a treatment-emergent adverse event (AE), including any subject who temporarily discontinued study drug due to an AE and did not restart. Results are expressed as proportions of participants who experience tolerability failure using the Kaplan-Meier (KM) method of estimation.
Time frame: Baseline to Week 168
Percent Probability of a Confirmed Increase in Serum Creatinine of ≥ 0.5 mg/dL From Baseline or a Confirmed Serum Phosphorus Level < 2.0 mg/dL
Results are expressed as proportions of participants who experience a confirmed increase in serum creatinine of ≥ 0.5 mg/dL from baseline or a confirmed serum phosphorus level \< 2.0 mg/dL using the KM method of estimation.
Time frame: Baseline to Week 168
Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline
Change from baseline was evaluated by subtracting baseline HBV DNA log_10 copies/mL from Week 48 HBV DNA log_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Time frame: Baseline to 48 weeks
Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline
Change from baseline was evaluated by subtracting baseline HBV DNA log_10 copies/mL from Week 96 HBV DNA log_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Time frame: Baseline to 96 weeks
Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline
Change from baseline was evaluated by subtracting baseline HBV DNA log_10 copies/mL from Week 144 HBV DNA log_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Time frame: Baseline to 144 weeks
Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline
Change from baseline was evaluated by subtracting baseline HBV DNA log_10 copies/mL from Week 168 HBV DNA log_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Time frame: Baseline to 168 weeks
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 48 was summarized.
Time frame: Week 48
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 96 was summarized.
Time frame: Week 96
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 144 was summarized.
Time frame: Week 144
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 168 was summarized.
Time frame: Week 168
Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48
Normalized ALT is defined as having a baseline ALT value \> the upper limit of the normal range (ULN), and a decrease in ALT value to ≤ ULN at the given time point.
Time frame: Baseline to Week 48
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
Time frame: Baseline to Week 96
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
Time frame: Baseline to Week 144
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
Time frame: Baseline to Week 168
Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 48
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 96
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 144
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 168
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 48
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 96
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 144
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 168
Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline to Week 48
Median Change in MELD Score From Baseline at Week 96
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline to Week 96
Median Change in MELD Score From Baseline at Week 144
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline to Week 144
Median Change in MELD Score From Baseline at Week 168
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline to Week 168
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline)
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Time frame: Baseline to Week 48
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline)
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Time frame: Baseline to Week 96
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline)
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Time frame: Baseline to Week 144
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline)
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Time frame: Baseline to Week 168
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Baseline to Week 48
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Baseline to Week 96
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Baseline to Week 144
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Baseline to Week 168
In the Subset of Participants Undergoing Liver Transplantation, Time to Recurrence of Hepatitis B, Defined as 2 Consecutive Plasma HBV DNA Concentrations ≥ 400 Copies/mL or 2 Consecutive HBsAg(+) Results
Time frame: Baseline to Week 168
Percentage of Participants With Only Baseline Adefovir Dipivoxil Resistance (ADV-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
ADV resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation.
Time frame: Baseline to Week 168
Percentage of Participants With Only Baseline Lamivudine-resistance (LAM-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
LAM resistance mutations are defined as the presence of the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation.
Time frame: Baseline to Week 168
Percentage of Participants With Baseline ADV-R + LAM-R Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
ADV resistance mutation + LAM resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation, and the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation.
Time frame: Baseline to Week 168
Of the 112 participants randomized, 43 were in Taiwan or Singapore, 43 were in Europe (Turkey, Spain, Germany, Greece, Poland, Italy, or France), and 26 were in the US or Canada. The first participant was screened on 04 April 2006, and the last participant was randomized on 03 January 2008. Last participant observation date was 12 April 2011.
| Milestone | Tenofovir DF | FTC/TDF | Entecavir |
|---|---|---|---|
| Started | 45 | 45 | 22 |
| Completed | 28 | 37 | 16 |
| Not completed | 17 | 8 | 6 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 |
| Withdrew: Physician decision | 4 | 1 | 0 |
| Withdrew: Protocol violation | 1 | 1 | 0 |
| Withdrew: Withdrawal by subject | 5 | 1 | 3 |
| Withdrew: Adverse event | 5 | 2 | 2 |
| Withdrew: Lack of efficacy | 2 | 3 | 0 |
Tolerability failure was defined as permanent discontinuation of study drug due to a treatment-emergent adverse event (AE), including any subject who temporarily discontinued study drug due to an AE and did not restart. Results are expressed as proportions of participants who experience tolerability failure using the Kaplan-Meier (KM) method of estimation.
| percent probability (KM estimate) | Tenofovir DF | FTC/TDF | TDF or FTC/TDF | Entecavir |
|---|---|---|---|---|
| Percent Probability of Tolerability Failure | 18 (5.8 to 30.6) | 4 (0.0 to 10.4) | 11 (4.1 to 17.7) | 14 (0.0 to 29.5) |
Change from baseline was evaluated by subtracting baseline HBV DNA log_10 copies/mL from Week 48 HBV DNA log_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
| log_10 copies/mL | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline | -2.93 (-3.84 to -2.18) | -3.45 (-4.73 to -2.02) | -3.61 (-4.51 to -1.31) | -3.19 (-4.52 to -2.08) |
Change from baseline was evaluated by subtracting baseline HBV DNA log_10 copies/mL from Week 96 HBV DNA log_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
| log_10 copies/mL | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline | -3.06 (-4.17 to -2.18) | -4.06 (-4.97 to -2.38) | -3.32 (-4.82 to -1.26) | -3.40 (-4.81 to -2.14) |
Change from baseline was evaluated by subtracting baseline HBV DNA log_10 copies/mL from Week 144 HBV DNA log_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
| log _10 copies/mL | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline | -3.07 (-4.36 to -2.00) | -3.82 (-4.99 to -2.06) | -3.76 (-5.00 to -1.33) | -3.49 (-4.91 to -2.05) |
Change from baseline was evaluated by subtracting baseline HBV DNA log_10 copies/mL from Week 168 HBV DNA log_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
| log_10 copies/mL | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline | -3.16 (-4.57 to -1.97) | -4.06 (-5.15 to -2.42) | -3.77 (-5.02 to -1.33) | -3.66 (-4.99 to -2.10) |
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 48 was summarized.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48 | 70.5 | 87.8 | 72.7 | 77.6 |
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 96 was summarized.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96 | 59.1 | 79.5 | 57.1 | 66.3 |
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 144 was summarized.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144 | 50.0 | 77.5 | 52.4 | 61.0 |
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 168 was summarized.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168 | 50.0 | 75.7 | 52.4 | 60.0 |
Normalized ALT is defined as having a baseline ALT value \> the upper limit of the normal range (ULN), and a decrease in ALT value to ≤ ULN at the given time point.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48 | 46.2 | 64.0 | 41.2 | 51.5 |
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96 | 50.0 | 58.3 | 31.3 | 48.5 |
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144 | 34.6 | 64.0 | 37.5 | 46.3 |
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168 | 29.2 | 60.0 | 37.5 | 43.1 |
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48 | 0.0 | 2.6 | 0.0 | 1.0 |
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96 | 0.0 | 0.0 | 0.0 | 0.0 |
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144 | 0.0 | 2.5 | 0.0 | 1.0 |
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168 | 2.4 | 0.0 | 0.0 | 1.0 |
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48 | 25.9 | 48.0 | 41.7 | 37.5 |
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96 | 23.1 | 52.0 | 50.0 | 39.3 |
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144 | 25.9 | 51.9 | 45.5 | 40.0 |
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168 | 24.0 | 45.8 | 45.5 | 36.7 |
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
| units on a scale | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48 | -2.0 (-3.0 to 0.0) | -2.0 (-4.0 to 0.0) | -2.0 (-4.0 to -1.0) | -2.0 (-3.0 to 0.0) |
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
| units on a scale | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Median Change in MELD Score From Baseline at Week 96 | -2.0 (-3.0 to 1.0) | -3.0 (-4.0 to 0.0) | -3.0 (-4.0 to -1.0) | -2.0 (-4.0 to 0.0) |
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
| units on a scale | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Median Change in MELD Score From Baseline at Week 144 | -2.0 (-3.5 to -0.5) | -1.5 (-6.0 to 0.0) | -2.0 (-5.0 to -1.0) | -2.0 (-4.0 to 0.0) |
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
| units on a scale | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| Median Change in MELD Score From Baseline at Week 168 | -2.0 (-4.0 to -1.0) | -2.0 (-4.0 to 0.0) | -2.0 (-5.0 to 0.0) | -2.0 (-4.0 to 0.0) |
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| HBeAg Loss | 21.4 | 26.7 | 0.0 | 19.4 |
| HBeAg Seroconversion | 21.4 | 13.3 | 0.0 | 13.9 |
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| HBeAg Loss | 14.3 | 33.3 | 0.0 | 20.0 |
| HBeAg Seroconversion | 14.3 | 13.3 | 0.0 | 11.4 |
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| HBeAg Loss | 14.3 | 33.3 | 16.7 | 22.9 |
| HBeAg Seroconversion | 14.3 | 13.3 | 0.0 | 11.4 |
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| HBeAg Loss | 23.1 | 35.7 | 16.7 | 27.3 |
| HBeAg Seroconversion | 23.1 | 21.4 | 0.0 | 18.2 |
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| HBsAg Loss | 0.0 | 0.0 | 0.0 | 0.0 |
| HBsAg Seroconversion | 0.0 | 0.0 | 0.0 | 0.0 |
ADV resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir |
|---|---|---|---|
| Percentage of Participants With Only Baseline Adefovir Dipivoxil Resistance (ADV-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | 100 | 100 | — |
LAM resistance mutations are defined as the presence of the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir |
|---|---|---|---|
| Percentage of Participants With Only Baseline Lamivudine-resistance (LAM-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | 100 | 100 | 100 |
ADV resistance mutation + LAM resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation, and the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir |
|---|---|---|---|
| Percentage of Participants With Baseline ADV-R + LAM-R Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | 50 | — | — |
Results are expressed as proportions of participants who experience a confirmed increase in serum creatinine of ≥ 0.5 mg/dL from baseline or a confirmed serum phosphorus level \< 2.0 mg/dL using the KM method of estimation.
| percent probability (KM estimate) | Tenofovir DF | FTC/TDF | TDF or FTC/TDF | Entecavir |
|---|---|---|---|---|
| Percent Probability of a Confirmed Increase in Serum Creatinine of ≥ 0.5 mg/dL From Baseline or a Confirmed Serum Phosphorus Level < 2.0 mg/dL | 15 (3.9 to 25.9) | 14 (3.6 to 24.4) | 14 (6.8 to 22.0) | 10 (0.0 to 22.8) |
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| HBsAg Loss | 0.0 | 0.0 | 0.0 | 0.0 |
| HBsAg Seroconversion | 0.0 | 0.0 | 0.0 | 0.0 |
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| HBsAg Loss | 0.0 | 0.0 | 0.0 | 0.0 |
| HBsAg Seroconversion | 0.0 | 0.0 | 0.0 | 0.0 |
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
| percentage of participants | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| HBsAg Loss | 0.0 | 0.0 | 0.0 | 0.0 |
| HBsAg Seroconversion | 0.0 | 0.0 | 0.0 | 0.0 |
| Days | Tenofovir DF | FTC/TDF | Entecavir | Overall |
|---|---|---|---|---|
| In the Subset of Participants Undergoing Liver Transplantation, Time to Recurrence of Hepatitis B, Defined as 2 Consecutive Plasma HBV DNA Concentrations ≥ 400 Copies/mL or 2 Consecutive HBsAg(+) Results | NA | NA | NA | NA |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Double Blind TDF | — | 21/45 (46.7%) | 41/45 (91.1%) |
| Double Blind FTC/TDF | — | 25/45 (55.6%) | 44/45 (97.8%) |
| Double Blind ETV | — | 11/22 (50%) | 20/22 (90.9%) |
| Open Label FTC/TDF | — | 4/12 (33.3%) | 9/12 (75%) |
| All TDF | — | 50/93 (53.8%) | 89/93 (95.7%) |
| Event | Double Blind TDF | Double Blind FTC/TDF | Double Blind ETV | Open Label FTC/TDF | All TDF |
|---|---|---|---|---|---|
| Hepatic neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 8/45 | 3/45 | 2/22 | 1/12 | 12/93 |
| Hepatic function abnormalHepatobiliary disorders | 2/45 | 5/45 | 2/22 | 0/12 | 7/93 |
| Hepatic encephalopathyNervous system disorders | 3/45 | 1/45 | 2/22 | 0/12 | 4/93 |
| AscitesGastrointestinal disorders | 3/45 | 3/45 | 1/22 | 1/12 | 7/93 |
| CholestasisHepatobiliary disorders | 0/45 | 0/45 | 0/22 | 1/12 | 1/93 |
| Hepatitis acuteHepatobiliary disorders | 0/45 | 0/45 | 0/22 | 1/12 | 1/93 |
| Pyelonephritis acuteInfections and infestations | 0/45 | 0/45 | 0/22 | 1/12 | 1/93 |
| Biliary anastomosis complicationInjury, poisoning and procedural complications | 0/45 | 0/45 | 0/22 | 1/12 | 1/93 |
| Calculus UretericRenal and urinary disorders | 0/45 | 0/45 | 0/22 | 1/12 | 1/93 |
| HydronephrosisRenal and urinary disorders | 0/45 | 0/45 | 0/22 | 1/12 | 1/93 |
| Event | Double Blind TDF | Double Blind FTC/TDF | Double Blind ETV | Open Label FTC/TDF | All TDF |
|---|---|---|---|---|---|
| AscitesGastrointestinal disorders | 8/45 | 4/45 | 6/22 | 1/12 | 13/93 |
| DiarrhoeaGastrointestinal disorders | 4/45 | 1/45 | 5/22 | 1/12 | 5/93 |
| Oedema peripheralGeneral disorders | 8/45 | 3/45 | 5/22 | 0/12 | 11/93 |
| HeadacheNervous system disorders | 4/45 | 3/45 | 5/22 | 1/12 | 8/93 |
| Abdominal pain upperGastrointestinal disorders | 9/45 | 7/45 | 2/22 | 2/12 | 18/93 |
| NauseaGastrointestinal disorders | 9/45 | 3/45 | 1/22 | 0/12 | 12/93 |
| InsomniaPsychiatric disorders | 9/45 | 4/45 | 4/22 | 1/12 | 14/93 |
| PyrexiaGeneral disorders | 6/45 | 5/45 | 4/22 | 0/12 | 11/93 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/45 | 4/45 | 4/22 | 2/12 | 8/93 |
| Hepatic neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 8/45 | 3/45 | 2/22 | 1/12 | 12/93 |
| Age Continuous(years) | Tenofovir DF | FTC/TDF | Entecavir | Total |
|---|---|---|---|---|
| Mean | 53 ± 8.8 | 49 ± 10.1 | 52 ± 12.0 | 51 ± 10.0 |
| Sex: Female, Male(Participants) | Tenofovir DF | FTC/TDF | Entecavir | Total |
|---|---|---|---|---|
| Female | 8 | 5 | 5 | 18 |
| Male | 37 | 40 | 17 | 94 |
| Region of Enrollment(participants) | Tenofovir DF | FTC/TDF | Entecavir | Total |
|---|---|---|---|---|
| France | 0 | 0 | 1 | 1 |
| United States | 10 | 2 | 2 | 14 |
| Taiwan | 13 | 16 | 9 | 38 |
| Greece | 4 | 1 | 1 | 6 |
| Canada | 4 | 7 | 1 | 12 |
| Poland | 2 | 2 | 2 | 6 |
| Spain | 2 | 6 | 2 | 10 |
| Singapore | 1 | 3 | 1 | 5 |
| Turkey | 4 | 6 | 2 | 12 |
| Germany | 4 | 1 | 1 | 6 |
| Italy | 1 | 1 | 0 | 2 |
| Race(participants) | Tenofovir DF | FTC/TDF | Entecavir | Total |
|---|---|---|---|---|
| Asian | 23 | 24 | 13 | 60 |
| Black | 1 | 1 | 0 | 2 |
| Other | 2 | 0 | 1 | 3 |
| White | 19 | 20 | 8 | 47 |
| Ethnicity(participants) | Tenofovir DF | FTC/TDF | Entecavir | Total |
|---|---|---|---|---|
| Hispanic or Latino | 2 | 1 | 0 | 3 |
| Not Hispanic or Latino | 39 | 39 | 21 | 99 |
| Not Permitted | 4 | 5 | 1 | 10 |
| Weight(kg) | Tenofovir DF | FTC/TDF | Entecavir | Total |
|---|---|---|---|---|
| Mean | 78.1 ± 17.02 | 74.4 ± 15.41 | 77.3 ± 16.64 | 76.5 ± 16.26 |
| Height(cm) | Tenofovir DF | FTC/TDF | Entecavir | Total |
|---|---|---|---|---|
| Mean | 168.3 ± 7.98 | 168.4 ± 8.47 | 167.1 ± 8.39 | 168.1 ± 8.20 |
| BMI(kg/m^2) | Tenofovir DF | FTC/TDF | Entecavir | Total |
|---|---|---|---|---|
| Mean | 27.6 ± 5.67 | 26.2 ± 5.07 | 27.6 ± 5.27 | 27.0 ± 5.35 |
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