Withdrawal of Therapy After Long-Term Antiviral Treatment for Chronic Hepatitis B
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|ClinicalTrials.gov Identifier: NCT01581554|
Recruitment Status : Completed
First Posted : April 20, 2012
Last Update Posted : April 10, 2023
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- Chronic infection with the hepatitis B virus may lead to cirrhosis, liver disease, and cancer of the liver. There is no cure for the infection, but several drugs have been approved to treat it. These drugs can keep the virus levels low. They seem to be safe for short-term use. But the drugs have not yet been approved for long-term use because some of them can have serious side effects. However, stopping treatment too soon can make the infection worse and may lead to more serious forms of liver disease. Researchers have not been able to determine a when to stop treatment. They want to study people with chronic hepatitis B infection to find out the best time to stop treatment and prevent the disease from causing further liver damage.
- To study the safety and effectiveness of withdrawing antiviral treatment for chronic hepatitis B after at least 4 years of treatment.
- To determine whether stopping long-term antiviral treatment for chronic hepatitis B makes the infection worse.
- People who are at least 18 years of age; have been taking antiviral drugs to treat chronic hepatitis B for at least 4 years; and are being evaluated to stop treatment.
- Those in the study will be screened with a physical exam, medical history, questionnaire, and blood tests. They will remain under the care of their regular doctor during the study.
- They will have an abdominal ultrasound to study scarring in the liver, if they have not had one in the past year.
- Those without detectable levels of the hepatitis B virus in their blood will stop antiviral treatment. They will have monthly blood tests for the first 6 months to check virus levels, and then every 3 months afterward.
- Those whose blood tests show an increase in virus levels will restart antiviral treatment as directed by the study doctors and their personal doctor.
- All those in the study will be monitored until the end of the study.
|Condition or disease|
|Chronic Hepatitis B e Antigen Positive Chronic Hepatitis B e Antigen Negative|
Chronic hepatitis B affects at least 1.5 million Americans and is a major cause of cirrhosis, end-stage liver disease and hepatocellular carcinoma. Five oral antiviral agents have been licensed for use in chronic hepatitis B in the United States. These agents are effective at suppressing viral replication, improving liver disease and reversing cirrhosis. The standard indications for starting antiviral therapy have been developed and widely accepted. Less clear is how long therapy should continue and when and under what conditions should therapy be stopped. Withdrawal after one year of therapy is commonly followed by relapse that in rare instances is severe and can be fatal. With longer courses of therapy, withdrawal of antiviral therapy has been associated with fewer and less severe relapses, but the criteria for stopping treatment are still unclear.
In this study, we propose to withdraw therapy in up to 50 patients with both HBeAg positive and negative chronic hepatitis B who have received a minimum of 4 years of oral nucleoside therapy with a serum HBV DNA level less than 500 IU/ml in the 6 months prior to withdrawal. After an outpatient evaluation, consenting patients will be withdrawn from therapy and followed carefully for presence of symptoms, abnormal liver tests and HBV DNA levels monthly for 6 months and every 3 months thereafter. Patients who relapse will be offered retreatment. Patients without relapse will be followed for at least four years after stopping therapy. The primary endpoint of the study will be the proportion of patients who maintain an HBV DNA < 1,000 IU/ml, and a serum ALT or AST<1.5 times the upper limit of normal one year off therapy. Secondary endpoints will be the proportion of patients who maintain HBeAg loss and clear HBsAg one year off therapy, the number of ALT or AST flares, predictors of maintained virological suppression and HBeAg negativity and the proportion of subjects who require re-initiation of therapy.
|Study Type :||Observational|
|Actual Enrollment :||15 participants|
|Official Title:||Withdrawal of Therapy After Long-Term Oral Nucleos(t)Ide Analogue Treatment in Patients With Chronic Hepatitis B|
|Actual Study Start Date :||May 18, 2011|
Patients with HBeAg negative chronic hepatitis B
Patients with HBeAg negative chronic hepatitis B who have received a minimum of 4 years of oral nucleoside therapy with a serum HBV DNA level less than 500 IU/ml in the 6 months prior to withdrawal.
Patients with HBeAG positive chronic hepatitis B
Patients with HBeAg positive chronic hepatitis B who have received a minimum of 4 years of oral nucleoside therapy with a serum HBV DNA level less than 500 IU/ml in the 6 months prior to withdrawal.
- Proportion of patients who maintain an HBV DNA <1.5 X the upper limit of normal one year off therapy [ Time Frame: One year after stopping therapy ]Proportion of patients who maintain an HBV DNA <1,000 IU/ml, and a serum ALT or AST <1.5 X the upper limit of normal one year off therapy
- Proportion of patients who maintain HBeAg loss and clear HBsAg one year off therapy [ Time Frame: One year after stopping therapy ]Proportion of patients who maintain HBeAg loss and clear HBsAg
- Number of ALT or AST flares [ Time Frame: One year after stopping therapy ]Number of ALT or AST flares
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
|Sampling Method:||Non-Probability Sample|
- INCLUSION CRITERIA:
Age greater than 18 years and older, male or female
HBsAg positive for greater than 6 months
For HBeAg positive subjects, HBeAg loss with or without anti-HBe with a minimum period of antiviral therapy for 48 weeks after HBeAg loss was first detected.
HBV DNA less than or equal to 500 IU/mL tested on at least 2 occasions over the last 6 months
Antiviral therapy for a minimum of 4 years
Baseline ALT or AST within the upper limit of normal.
Willing and able to provide written, informed consent.
Subjects must be eligible to enter protocol 07-DK-0207 or be willing to be treated by their local physician should relapse or a hepatitis flare occur.
Presence of cirrhosis (Ishak fibrosis score 5 or 6) on any liver biopsy performed within the last 4 years. In the absence of a liver biopsy then any three of the following five variables: platelet count less than or equal to 100,000/mm(3), reversal of ALT/AST ratio, total bilirubin greater than 2.0 mg/dL, splenomegaly on ultrasound and presence of esophageal or gastric varices or portal hypertensive gastropathy on endoscopy
Any history of decompensated liver disease
Prior or current therapy with tenofovir or tenofovir plus emtricitabine
Renal insufficiency defined as a serum creatinine greater than 1.5 mg/dL or an estimated glomerular filtration rate less than or equal to 50 mls/minute using the Cockroft and Gault formula.
Anti-hepatitis C virus positivity
Anti-hepatitis D virus positivity
Anti-human immunodeficiency virus positivity
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01581554
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Marc G Ghany, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Responsible Party:||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Other Study ID Numbers:||
|First Posted:||April 20, 2012 Key Record Dates|
|Last Update Posted:||April 10, 2023|
|Last Verified:||March 10, 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Hepatitis B, Chronic
Digestive System Diseases
Hepatitis, Viral, Human
RNA Virus Infections
DNA Virus Infections