Tenofovir Alone Versus Tenofovir With Emtricitabine to Treat Chronic Hepatitis B
This study will test whether the combination of two medications, tenofovir and emtricitabine, are safer and more effective for treating chronic hepatitis B than tenofovir alone. Chronic hepatitis B is a liver disease caused by infection with the hepatitis B virus. Several medications, including standard and pegylated interferon and the anti-viral drugs lamivudine, adefovir, entecavir and telbivudine, are currently used to treat the disease. Problems are associated with all of these agents, however, including development of viral resistance with long-term therapy of the anti-virals. Since many patients require long-term therapy to prevent their disease from worsening, a major goal of new approaches to treatment is to prevent the development of viral resistance. Combination treatment has been shown to be an effective strategy in preventing this resistance.
Tenofovir is an anti-viral drug approved for use in patients with HIV infection. In small studies in patients infected with both HIV and hepatitis B, tenofovir lowered the level of hepatitis B virus in the blood, with no viral resistance reported when used for up to 5 years. Emtricitabine is an anti-viral drug similar to lamivudine and is effective at lowering viral load and improving liver damage.
Patients 18 years of age and older with chronic hepatitis B may be eligible for this study. Participants are admitted to the NIH Clinical Center for a complete medical history and examination, including blood and urine tests, chest X-ray, electrocardiogram, abdominal ultrasound, Fibroscan (ultrasound exam of the liver that measures the amount of scarring), bone mineral density scan and liver biopsy. They are then randomly assigned to take combination treatment with tenofovir plus emtricitabine or tenofovir alone for at least 48 weeks. During the treatment period, patients visit the Clinical Center for blood tests and a physical examination every 2 weeks for the first month and then every 4 to 12 weeks. After 48 weeks, patients are readmitted to the Clinical Center for a complete evaluation that includes all the tests done at the start of therapy, including a liver biopsy. Patients who seem to have improved with treatment may continue therapy for up to 192 weeks, when they are again admitted to the Clinical Center for a complete medical evaluation and liver biopsy. Patients whose condition has not improved after 48 weeks of treatment have their treatment changed or stopped and continue to have regular outpatient clinic visits for 24 more weeks.
Chronic Hepatitis B e Antigen Positive
Chronic Hepatitis B e Antigen Negative
Drug: Tenofovir/ & amp; Emtricitabine
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Tenofovir Disoproxil Fumarate Alone Versus Its Combination With Emtricitabine for Treatment of Chronic Hepatitis B|
- Maintained suppression of HBV DNA below 102 copies/ml (& lt; 95 IU/ml, undetectable by current PCR-based assays, Roche Amplicor assay). [ Designated as safety issue: No ]
- Normalization of ALT levels and histological improvements which are expected to occur in all patients with full suppression of HBV DNA and in a proportion of those with partial suppression. Other endpoints will be loss of HBeAg and loss of HBsA... [ Designated as safety issue: No ]
|Study Start Date:||August 2007|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Drug: Tenofovir/ & amp; Emtricitabine
Chronic hepatitis B is a major cause of cirrhosis, end-stage liver disease and hepatocellular carcinoma and affects approximately 1.25 million Americans. Six medications have been licensed for use in chronic hepatitis B in the United States, but their relative benefit and long-term efficacy remain unclear. In previous studies, we have shown that maintained suppression of HBV DNA can be achieved with nucleoside analogues and that suppression is associated with marked improvements in disease. In this randomized study, we propose to evaluate long-term therapy with tenofovir alone or in combination with emtricitabine (FTC). Forty treatment-naive patients with chronic hepatitis B will be enrolled in the primary study. After medical evaluation and liver biopsy, patients will be stratified by hepatitis B e antigen (HBeAg) status and randomized to receive either tenofovir alone or in combination with FTC. Treatment will be continued long-term (at least four years) and patients will be carefully monitored for side effects, serum aminotransferase and HBV DNA levels. Patients will undergo repeat liver biopsy and assessment of antiviral resistance at 1 and 4 years. The primary endpoint of therapy will be the maintained suppression of HBV DNA to below 10(2) copies/ml (lower limit of detection of current assays). The study will assess the relative efficacy and safety of combination versus mono-therapy. A separate group of 60 previously treated patients will also be enrolled and randomized to mono- or combination-therapy to assess the safety profile of these agents. The primary analysis will be conducted on the entire study cohort.
|Contact: Elenita Rivera, R.N.||(301) firstname.lastname@example.org|
|Contact: Marc G Ghany, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Marc G Ghany, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|