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Lamivudine and Adefovir to Treat Chronic Hepatitis B

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ClinicalTrials.gov Identifier: NCT00023309
Recruitment Status : Completed
First Posted : September 3, 2001
Results First Posted : April 4, 2013
Last Update Posted : September 23, 2016
Sponsor:
Information provided by (Responsible Party):
Marc Ghany, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HBV (Hepatitis B Virus)
Hepatitis B
Hepatitis
Interventions Drug: Lamivudine and adefovir
Drug: Adefovir alone
Enrollment 41
Recruitment Details Forty-one patients were enrolled, twenty-two were randomized to receive the combination lamivudine and adefovir and nineteen to receive adefovir alone.
Pre-assignment Details  
Arm/Group Title Lamivudine and Adefovir Adefovir
Hide Arm/Group Description Patients to receive combination lamivudine and adefovir, with lamivudine of 100 mg daily and adefovir of 10 mg daily Patients to receive adefovir alone (10 mg daily).
Period Title: Overall Study
Started 22 19
Completed 22 19
Not Completed 0 0
Arm/Group Title Lamivudine and Adefovir Adefovir Total
Hide Arm/Group Description Patients to receive combination lamivudine and adefovir Patients to receive adefovir alone Total of all reporting groups
Overall Number of Baseline Participants 22 19 41
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 19 participants 41 participants
46  (14) 45  (13) 45  (14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 19 participants 41 participants
Female
6
  27.3%
1
   5.3%
7
  17.1%
Male
16
  72.7%
18
  94.7%
34
  82.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants 19 participants 41 participants
White 9 8 17
Asian 9 10 19
Black 4 1 5
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 22 participants 19 participants 41 participants
22 19 41
Treatment Naive  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants 19 participants 41 participants
Yes 17 14 31
No 5 5 10
HBeAg positive  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants 19 participants 41 participants
Yes 17 14 31
No 5 5 10
ALT   [1] 
Mean (Standard Deviation)
Unit of measure:  IU/ml
Number Analyzed 22 participants 19 participants 41 participants
183  (250) 87  (56) 139  (187)
[1]
Measure Description: Alanine transaminase
HBV DNA Log 10 copies per ml   [1] 
Mean (Standard Deviation)
Unit of measure:  Log10(copies/ml)
Number Analyzed 22 participants 19 participants 41 participants
8.1  (1.3) 7.8  (1.6) 8.0  (1.4)
[1]
Measure Description: Hepatitis B virus DNA logarithm 10 copies per ml
HAI   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 22 participants 19 participants 41 participants
8.1  (2.7) 7.9  (2.4) 8.0  (2.6)
[1]
Measure Description: HAI Fibrosis score for liver histology, which has a range 0–18 and higher values represent a worse outcome
Ishak   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 22 participants 19 participants 41 participants
3.3  (1.7) 2.4  (1.5) 2.9  (1.6)
[1]
Measure Description: Ishak Fibrosis Score, (range 0–6, where 0 = no fibrosis and 6 = cirrhosis)
Cirrhosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants 19 participants 41 participants
Yes 5 2 7
No 17 17 34
1.Primary Outcome
Title Maintained Combined Response (Virological, Biochemical and Histological Response).
Hide Description A maintained combined response was defined as a combination of a virological, biochemical and histological responses at weeks 48 and 192. A virological response was defined as a decrease in HBV DNA levels to undetectable by the Amplicor assay (<500 copies/mL). A biochemical response was defined as a decrease in serum ALT levels into the normal range (<41 U/L). A histological response was defined as a decrease in the HAI score by at least three points with no worsening of the Ishak fibrosis score.
Time Frame 196 weeks from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was intention to treat. Patients with missing values at week 196 were treated as random missing. No imputation was applied.
Arm/Group Title Lamivudine and Adefovir Adefovir
Hide Arm/Group Description:
Patients to receive combination lamivudine and adefovir
Patients to receive adefovir alone
Overall Number of Participants Analyzed 22 19
Measure Type: Number
Unit of Measure: participants
Yes 15 6
No 7 13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lamivudine and Adefovir, Adefovir
Comments Null hypothesis: there is no difference in the treatment effect between the two groups
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0294
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title HBeAg Loss at Week 196
Hide Description Loss of hepatitis B surface antigen (HBsAg) at week 196
Time Frame Week 196 from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was intention to treat. Patients with missing values at timeframe of interest was taken as random missing. No imputation was applied.
Arm/Group Title Lamivudine and Adefovir Adefovir
Hide Arm/Group Description:
Patients to receive combination lamivudine and adefovir
Patients to receive adefovir alone
Overall Number of Participants Analyzed 17 14
Measure Type: Number
Unit of Measure: participants
Yes 13 5
No 4 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lamivudine and Adefovir, Adefovir
Comments Null hypothesis: there is no difference in treatment effect at week 196
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0325
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Virological Response
Hide Description A virological response was defined as a decrease in HBV DNA levels to undetectable by the Amplicor assay (<500 copies/mL).
Time Frame Week 196 from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat
Arm/Group Title Lamivudine and Adefovir Adefovir
Hide Arm/Group Description:
Patients to receive combination lamivudine and adefovir
Patients to receive adefovir alone
Overall Number of Participants Analyzed 22 19
Measure Type: Number
Unit of Measure: participants
Yes 17 6
No 5 13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lamivudine and Adefovir, Adefovir
Comments Null hypothesis: there is no difference in treatment effect at week 196
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0049
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Biological Response
Hide Description A biochemical response was defined as a decrease in serum ALT levels into the normal range (<41 U/L).
Time Frame week 196 from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat
Arm/Group Title Lamivudine and Adefovir Adefovir
Hide Arm/Group Description:
Patients to receive combination lamivudine and adefovir
Patients to receive adefovir alone
Overall Number of Participants Analyzed 22 19
Measure Type: Number
Unit of Measure: participants
Yes 21 12
No 1 7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lamivudine and Adefovir, Adefovir
Comments Null hypothesis: there is no difference in treatment effect at week 196
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0157
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Histological Response
Hide Description A histological response was defined as a decrease in the HAI score by at least three points with no worsening of the Ishak fibrosis score.
Time Frame week 196 from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was intention to treat. Patients with missing values at timeframe of interest was taken as random missing. No imputation was applied.
Arm/Group Title Lamivudine and Adefovir Adefovir
Hide Arm/Group Description:
Patients to receive combination lamivudine and adefovir
Patients to receive adefovir alone
Overall Number of Participants Analyzed 18 10
Measure Type: Number
Unit of Measure: participants
Yes 15 5
No 3 5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lamivudine and Adefovir, Adefovir
Comments Null hypothesis: there is no difference in treatment effect at week 196
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0913
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lamivudine and Adefovir Adefovir
Hide Arm/Group Description Patients to receive combination lamivudine and adefovir Patients to receive adefovir alone
All-Cause Mortality
Lamivudine and Adefovir Adefovir
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Lamivudine and Adefovir Adefovir
Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)   0/19 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lamivudine and Adefovir Adefovir
Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)   0/19 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Marc G. Ghany, M.D
Organization: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Phone: 3014961721
Responsible Party: Marc Ghany, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00023309     History of Changes
Other Study ID Numbers: 010246
01-DK-0246 ( Other Identifier: NIHCC )
First Submitted: September 3, 2001
First Posted: September 3, 2001
Results First Submitted: July 7, 2011
Results First Posted: April 4, 2013
Last Update Posted: September 23, 2016