Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00023309
Status:
COMPLETED
Last Update Posted:
2016-09-23
First Post:
2001-09-03
Brief Title:
Lamivudine and Adefovir to Treat Chronic Hepatitis B
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Combination of Lamivudine and Adefovir Dipivoxil for Treatment of Chronic Hepatitis B
Status:
COMPLETED
Status Verified Date:
2014-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the safety and effectiveness of lamivudine plus adefovir versus adefovir alone to treat chronic hepatitis B infection The Food and Drug Administration has approved lamivudine for the treatment of hepatitis B However the drug is not effective in all patients and many of those in whom it initially works develop resistance after 1 to 3 years Adefovir is an experimental drug that inhibits replication of the hepatitis B virus HBV Adefovir used alone may be adequate to provide sustained suppression of the virus and improvement in liver disease However combining two anti-viral agents may be superior to using one alone similar to the strategy employed for the treatment of AIDS This study will test whether the combination of lamivudine and adefovir is better than adefovir alone for the treatment of chronic hepatitis B
Patients 18 years of age and older who have been infected with HBV for at least 6 months may be eligible for this study Candidates may not have received lamivudine treatment in the past 6 months or prior treatment with adefovir and must not be taking other anti-viral treatments for their hepatitis They will have a blood test to confirm HBV infection
Participants will be admitted to the NIH Clinical Center for 2 to 3 days for a medical evaluation One to 2 weeks after the evaluation patients will be randomized to begin taking lamivudine and adefovir or adefovir alone Therapy will continue for at least 12 months Follow-up clinic visits will be scheduled weekly for the first month then every 4 to 8 weeks for the rest of the treatment period Patients will be evaluated at the end of 1 year Patients who have not improved with treatment will stop taking the treatment and will be evaluated in the clinic once every 4 weeks for another 6 months Patients who show an improvement in their liver injury may continue taking lamivudine and adefovir or adefovir alone for 4 more years as long as they continue to improve with the medication Progress will be evaluated If the test results show no continued improvement or are negative for hepatitis B antigens therapy will be stopped
Patients who continue treatment for 5 years will be readmitted at year 4 for another medical evaluation to assess the effects of treatment at that time After the 5 years all patients will stop therapy at and be followed with regular clinic visits for at least 6 months
Patients 18 years of age and older who have been infected with HBV for at least 6 months may be eligible for this study Candidates may not have received lamivudine treatment in the past 6 months or prior treatment with adefovir and must not be taking other anti-viral treatments for their hepatitis They will have a blood test to confirm HBV infection
Participants will be admitted to the NIH Clinical Center for 2 to 3 days for a medical evaluation One to 2 weeks after the evaluation patients will be randomized to begin taking lamivudine and adefovir or adefovir alone Therapy will continue for at least 12 months Follow-up clinic visits will be scheduled weekly for the first month then every 4 to 8 weeks for the rest of the treatment period Patients will be evaluated at the end of 1 year Patients who have not improved with treatment will stop taking the treatment and will be evaluated in the clinic once every 4 weeks for another 6 months Patients who show an improvement in their liver injury may continue taking lamivudine and adefovir or adefovir alone for 4 more years as long as they continue to improve with the medication Progress will be evaluated If the test results show no continued improvement or are negative for hepatitis B antigens therapy will be stopped
Patients who continue treatment for 5 years will be readmitted at year 4 for another medical evaluation to assess the effects of treatment at that time After the 5 years all patients will stop therapy at and be followed with regular clinic visits for at least 6 months
Detailed Description:
Aims To assess the safety antiviral activity and clinical benefit of the combination of lamivudine and adefovir dipivoxil vs adefovir alone in up to 80 patients with chronic hepatitis B for up to five years
Background Adefovir dipivoxil and lamivudine are oral antiviral agents that have been shown to have potent activity against HBV in vitro and in vivo Both drugs have been used extensively in patients with HIV infection and more recently in controlled trials as monotherapy in patients with chronic hepatitis B Lamivudine is currently approved as therapy of hepatitis B and has been evaluated extensively both as a one-year course of treatment as well as long-term continuous therapy While lamivudine monotherapy induces a transient improvement in viral levels and liver histology viral resistance develops in a large proportion of patients with re-appearance of HBV DNA in serum in high levels associated with mutations in the Tyrosine-methionine-aspartate-aspartate YMDD motif of the HBV polymerase gene and worsening of the hepatitis Adefovir monotherapy in contrast has not been shown to be associated with development of viral resistance even when given for up to two years When given as monotherapy for 1 year adefovir leads to improvement in histology of hepatitis B in approximately 50 of patients At present the long-term efficacy of adefovir has not been shown
Protocol Up to 80 patients with chronic hepatitis B who have raised serum ALT alanine aminotransferase levels HBV DNA in serum above 1 million copies per ml by quantitative PCR and active liver disease on liver biopsy will be enrolled and started on the combination of lamivudine 100 mg daily and adefovir dipivoxil 10 mg daily or adefovir alone 10 mg daily Patients will be stratified into one of four groups of 20 patients for randomization A Lamivudine naive and HBeAg positive B Lamivudine naive and HBeAg negative C previous lamivudine therapy and HBeAg positive and D previous lamivudine therapy and HBeAg negative Patients will be monitored carefully during therapy for adverse events clinical symptoms and signs of liver disease biochemical and hematological parameters and HBV serology at 2 to 4 week intervals The primary endpoint of therapy will be a maintained combined response a combination of virological biochemical and histological response with major timing of end-points being at 1 and 4 years Secondary endpoints will include loss of HBeAg the individual types of maintained responses virological biochemical and histological the development of lamivudine resistance and improvement in symptom scores and quality of life assessments at 1 and 4 years
Conclusions This study will assess the effects of the combination of lamivudine and adefovir dipivoxil compared to adefovir alone in suppressing hepatitis B and prevention of lamivudine resistant mutants that arise during long-term therapy with lamivudine alone
Background Adefovir dipivoxil and lamivudine are oral antiviral agents that have been shown to have potent activity against HBV in vitro and in vivo Both drugs have been used extensively in patients with HIV infection and more recently in controlled trials as monotherapy in patients with chronic hepatitis B Lamivudine is currently approved as therapy of hepatitis B and has been evaluated extensively both as a one-year course of treatment as well as long-term continuous therapy While lamivudine monotherapy induces a transient improvement in viral levels and liver histology viral resistance develops in a large proportion of patients with re-appearance of HBV DNA in serum in high levels associated with mutations in the Tyrosine-methionine-aspartate-aspartate YMDD motif of the HBV polymerase gene and worsening of the hepatitis Adefovir monotherapy in contrast has not been shown to be associated with development of viral resistance even when given for up to two years When given as monotherapy for 1 year adefovir leads to improvement in histology of hepatitis B in approximately 50 of patients At present the long-term efficacy of adefovir has not been shown
Protocol Up to 80 patients with chronic hepatitis B who have raised serum ALT alanine aminotransferase levels HBV DNA in serum above 1 million copies per ml by quantitative PCR and active liver disease on liver biopsy will be enrolled and started on the combination of lamivudine 100 mg daily and adefovir dipivoxil 10 mg daily or adefovir alone 10 mg daily Patients will be stratified into one of four groups of 20 patients for randomization A Lamivudine naive and HBeAg positive B Lamivudine naive and HBeAg negative C previous lamivudine therapy and HBeAg positive and D previous lamivudine therapy and HBeAg negative Patients will be monitored carefully during therapy for adverse events clinical symptoms and signs of liver disease biochemical and hematological parameters and HBV serology at 2 to 4 week intervals The primary endpoint of therapy will be a maintained combined response a combination of virological biochemical and histological response with major timing of end-points being at 1 and 4 years Secondary endpoints will include loss of HBeAg the individual types of maintained responses virological biochemical and histological the development of lamivudine resistance and improvement in symptom scores and quality of life assessments at 1 and 4 years
Conclusions This study will assess the effects of the combination of lamivudine and adefovir dipivoxil compared to adefovir alone in suppressing hepatitis B and prevention of lamivudine resistant mutants that arise during long-term therapy with lamivudine alone
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-DK-0246 | OTHER | NIHCC | None |