Withdrawal of Therapy After Long-Term Antiviral Treatment for Chronic Hepatitis B
|First Received Date ICMJE||April 19, 2012|
|Last Updated Date||December 6, 2013|
|Start Date ICMJE||April 2011|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01581554 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Withdrawal of Therapy After Long-Term Antiviral Treatment for Chronic Hepatitis B|
|Official Title ICMJE||Withdrawal of Therapy After Long-Term Oral Nucleos(t)Ide Analogue Treatment in Patients With Chronic Hepatitis B|
- 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.
- 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.
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 ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||50|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01581554|
|Other Study ID Numbers ICMJE||110151, 11-DK-0151|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||October 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP