HIV InfectionsPhase 2NCT00051077
Treatment of Hepatitis in Patients Who Are Triple-Infected With HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV)
A Phase 2 study testing Adefovir dipivoxil, Peginterferon-alfa-2A and Ribavirin in people with HIV Infections and Hepatitis B, run by National Institute of Allergy and Infectious Diseases (NIAID).
Trial summary
This study will investigate the safety and effectiveness of using adefovir dipivoxil (ADV), pegylated interferon (PEG-INF), and ribavirin (RBV) in patients triple-infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. Patients in this study must be taking lamivudine (3TC). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infections, Hepatitis B, Hepatitis C
- What is being tested?
- Adefovir dipivoxil, Peginterferon-alfa-2A and Ribavirin
- Type of treatment
- Surgery or procedure
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Start not givento not given
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV positive
- Documented HCV viremia within 48 weeks prior to study entry
- HBV DNA >= 500,000 copies/ml within 12 weeks prior to study entry
- Chronic viral liver disease as documented by liver biopsy within 52 weeks prior to study entry
- Treated with 3TC for at least 26 weeks prior to study entry
- CD4+ count >200 cells/mm3 within 35 days prior to study entry
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- HIV-1 viral load of <55,000 copies/ml within 35 days prior to entry
- Either have been on stable antiretroviral therapy for at least 12 weeks prior to study entry and plan to remain on same antiretroviral therapy OR have not received any antiretroviral therapy in the 12 weeks prior to the study and do not plan to begin antiretroviral therapy during the first 12 weeks of the study
- Acceptable methods of contraception
Who cannot join
- History of any medical condition associated with chronic liver disease other than viral hepatitis
- History of ALT elevations over 3 X baseline level
- Child-Pugh-Turcotte (CPT) score > 5
- Previous suicide attempt or hospitalization for psychiatric illness within 2 years prior to study entry
- History of hypersensitivity to RBV, interferon, or other components of study medications
- Uncontrolled seizure disorder
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- Certain medical conditions, including hepatitis D, autoimmune disorders, Chronic Obstructive Pulmonary Disease, cardiac disease, cancer, hemoglobinopathy, major organ transplant, kidney disease, opportunistic infection, and retinopathy
- Certain medications
- Pregnancy or breast-feeding
- Male partners of women who are pregnant
- Active drug or alcohol use or dependence
About this study
Official title: A Phase II Study of Adefovir Dipivoxil, Pegylated Interferon Alfa-2A, and Ribavirin Treatment in HBV and HCV Infected Subjects With HIV Disease
This study will investigate the safety and effectiveness of using adefovir dipivoxil (ADV), pegylated interferon (PEG-INF), and ribavirin (RBV) in patients triple-infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. Patients in this study must be taking lamivudine (3TC).
Read the detailed description
The emergence of liver disease in HIV infected patients with coinfections of HBV and/or HCV has become increasingly important in disease progression in the post-HAART (highly active antiretroviral therapy) era. The overall rate of HBV and HCV infection in HIV infected persons is 5% to 10%. There is convincing evidence that HIV infection exacerbates the severity of viral hepatitis and the progression of liver disease. Hepatitis treatment studies have generally excluded HIV patients with both HBV and HCV. As such, the influence of HBV on HCV treatment in HIV infected patients is unknown. This study will investigate the safety and anti-HBV efficacy of ADV + PEG-INF + RBV triple therapy in patients with HCV, HIV, and 3TC-resistant HBV. The study will also evaluate the effect of HBV and HBV therapy on HCV and HIV disease progression.
Patients with documented HIV, 3TC-resistant HBV, and HCV will be randomized to one of two treatment regimens for 48 weeks. Patients in both groups will receive daily oral RBV and weekly subcutaneous injections of PEG-INF. Patients in Group A will receive daily ADV; patients in Group B will receive placebo. After 48 weeks of study treatment, all study medications will be discontinued and patients will undergo liver biopsy. Patients will then be followed for an additional 24 weeks. Throughout the study, investigators will monitor numerous lab values and patients will be asked to complete multiple adherence questionnaires. Subjects who have a confirmed 2 point increase in Child-Pugh-Turcotte liver disease prognosis score at any time during the study will permanently discontinue PEG-INF and RBV and register to Step 2 to receive open label ADV.
- Conditions
- HIV Infections, Hepatitis B, Hepatitis C
- Being tested
- Adefovir dipivoxil, Peginterferon-alfa-2A, Ribavirin, Liver Biopsy
- Keywords
- HIV Infections, Hepatitis B, Hepatitis C, Interferon Alfa-2a, Adefovir dipivoxil, Ribavirin, Antiviral Agents, Drug Resistance, Viral, Treatment Experienced
- Medical subject headings
- HIV Infections, Hepatitis B, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adefovir dipivoxilDrug
Peginterferon-alfa-2ADrug
RibavirinDrug
Liver BiopsyProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2003 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Dickens Theodore, M.D., Ph.D., Study chair, University of North Carolina, Chapel HillKenneth E Sherman, M.D., Ph.D, Study chair, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00051077
- Sponsor's protocol ID
- A5149
- Other IDs
- 10953, ACTG A5149
- Status last verified
- Oct 2021
- First submitted
- 3 Jan 2003
- Last updated
- 1 Nov 2021
- Results posted
- No
Publications
Benhamou Y, Bochet M, Thibault V, Calvez V, Fievet MH, Vig P, Gibbs CS, Brosgart C, Fry J, Namini H, Katlama C, Poynard T. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet. 2001 Sep 1;358(9283):718-23. doi: 10.1016/s0140-6736(01)05840-8.
PubMed 11551579Soriano V, Garcia-Samaniego J, Bravo R, Gonzalez J, Castro A, Castilla J, Martinez-Odriozola P, Colmenero M, Carballo E, Suarez D, Rodriguez-Pinero FJ, Moreno A, del Romero J, Pedreira J, Gonzalez-Lahoz J. Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group. Clin Infect Dis. 1996 Sep;23(3):585-91. doi: 10.1093/clinids/23.3.585.
PubMed 8879784Xiong X, Flores C, Yang H, Toole JJ, Gibbs CS. Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro. Hepatology. 1998 Dec;28(6):1669-73. doi: 10.1002/hep.510280629.
PubMed 9828233McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998 Nov 19;339(21):1485-92. doi: 10.1056/NEJM199811193392101.
PubMed 9819446
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Adefovir Dipivoxil, Pegylated Interferon Alfa-2A, and Ribavirin Treatment in HBV and HCV Infected Subjects With HIV Disease
- ClinicalTrials.gov ID
- NCT00051077
- Acronym / sponsor ID
- A5149
- Conditions
- HIV Infections, Hepatitis B, Hepatitis C
- Keywords
- HIV Infections, Hepatitis B, Hepatitis C, Interferon Alfa-2a, Adefovir dipivoxil, Ribavirin, Antiviral Agents, Drug Resistance, Viral
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- First posted
- 6 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the safety and effectiveness of using adefovir dipivoxil (ADV), pegylated interferon (PEG-INF), and ribavirin (RBV) in patients triple-infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. Patients in this study must be taking lamivudine (3TC).
Detailed description
The emergence of liver disease in HIV infected patients with coinfections of HBV and/or HCV has become increasingly important in disease progression in the post-HAART (highly active antiretroviral therapy) era. The overall rate of HBV and HCV infection in HIV infected persons is 5% to 10%. There is convincing evidence that HIV infection exacerbates the severity of viral hepatitis and the progression of liver disease. Hepatitis treatment studies have generally excluded HIV patients with both HBV and HCV. As such, the influence of HBV on HCV treatment in HIV infected patients is unknown. This study will investigate the safety and anti-HBV efficacy of ADV + PEG-INF + RBV triple therapy in patients with HCV, HIV, and 3TC-resistant HBV. The study will also evaluate the effect of HBV and HBV therapy on HCV and HIV disease progression.
Patients with documented HIV, 3TC-resistant HBV, and HCV will be randomized to one of two treatment regimens for 48 weeks. Patients in both groups will receive daily oral RBV and weekly subcutaneous injections of PEG-INF. Patients in Group A will receive daily ADV; patients in Group B will receive placebo. After 48 weeks of study treatment, all study medications will be discontinued and patients will undergo liver biopsy. Patients will then be followed for an additional 24 weeks. Throughout the study, investigators will monitor numerous lab values and patients will be asked to complete multiple adherence questionnaires. Subjects who have a confirmed 2 point increase in Child-Pugh-Turcotte liver disease prognosis score at any time during the study will permanently discontinue PEG-INF and RBV and register to Step 2 to receive open label ADV.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- HIV positive
- Documented HCV viremia within 48 weeks prior to study entry
- HBV DNA >= 500,000 copies/ml within 12 weeks prior to study entry
- Chronic viral liver disease as documented by liver biopsy within 52 weeks prior to study entry
- Treated with 3TC for at least 26 weeks prior to study entry
Key exclusion criteria (11 listed)
- History of any medical condition associated with chronic liver disease other than viral hepatitis
- History of ALT elevations over 3 X baseline level
- Child-Pugh-Turcotte (CPT) score > 5
- Previous suicide attempt or hospitalization for psychiatric illness within 2 years prior to study entry
- History of hypersensitivity to RBV, interferon, or other components of study medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adefovir dipivoxil | Drug | – |
| Peginterferon-alfa-2A | Drug | – |
| Ribavirin | Drug | – |
| Liver Biopsy | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Background: PubMed 11551579Benhamou Y, Bochet M, Thibault V, Calvez V, Fievet MH, Vig P, Gibbs CS, Brosgart C, Fry J, Namini H, Katlama C, Poynard T. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet. 2001 Sep 1;358(9283):718-23. doi: 10.1016/s0140-6736(01)05840-8.
- Background: PubMed 8879784Soriano V, Garcia-Samaniego J, Bravo R, Gonzalez J, Castro A, Castilla J, Martinez-Odriozola P, Colmenero M, Carballo E, Suarez D, Rodriguez-Pinero FJ, Moreno A, del Romero J, Pedreira J, Gonzalez-Lahoz J. Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group. Clin Infect Dis. 1996 Sep;23(3):585-91. doi: 10.1093/clinids/23.3.585.
- Background: PubMed 9828233Xiong X, Flores C, Yang H, Toole JJ, Gibbs CS. Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro. Hepatology. 1998 Dec;28(6):1669-73. doi: 10.1002/hep.510280629.
- Background: PubMed 9819446McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998 Nov 19;339(21):1485-92. doi: 10.1056/NEJM199811193392101.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dickens Theodore, M.D., Ph.D. study chair
University of North Carolina, Chapel Hill
Kenneth E Sherman, M.D., Ph.D study chair
University of Cincinnati
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adefovir dipivoxil, Peginterferon-alfa-2A and Ribavirin in people with HIV Infections and Hepatitis B, run by National Institute of Allergy and Infectious Diseases (NIAID).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00051077, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.