View clinical trials related to Chronic Hepatitis B.
Filter by:The study was conducted to evaluate the effect of anti-viral treatment on long-term outcome on patients with chronic hepatitis B.
The objective of the study is to procure blood (plasma, serum, RNA and PBMC samples) from approximately 40 chronic HBV for biomedical research program led by VGTI Florida.
This research puts liver biopsy as the enrollment screening criteria and the primary efficacy assessment indicators. Patients at different developmental stages of hepatitis B related liver fibrosis are respectively diagnosed and treated by Traditional Chinese medicine to determine optional diagnosis and treatment plan of traditional Chinese medicine to screen the advantage-treated population and to establish a treatment program, which can save national medical resources, for clinical application of Traditional Chinese medicine Diagnosis and Treatment blocking and reversing hepatitis B-related liver fibrosis. The research can help to build automation pathological analysis and diagnosis systems and non-invasive clinical assessment criteria and models of liver fibrosis which can be applied in clinical. It can also help to realize electronic patient data collection and management, to establish patients management centre and follow-up database. Then it will help to improve clinical efficacy of being blocked and reversed chronic hepatitis B related liver fibrosis by Chinese medicine Diagnosis and Treatment program, to reduce the incidence of liver cirrhosis and hepatitis B-related mortality, to prolong patients' survival and improve patients' quality of life, to make clinical efficacy, which is about Traditional Chinese Medicine blocking and revering chronic hepatitis B-related liver fibrosis, increase by 15% or more .
Currently, there are several antiviral treatments effective for suppression of viral replication but still failed to cure HBV infection in patients with chronic hepatitis B (CHB). Seven drugs have been worldwide approved for the treatment of CHB at present: conventional IFN (IFN) alfa, lamivudine (LAM), adefovir dipivoxil (ADV), pegylated IFN (Peg-IFN) alfa, entecavir (ETV), telbivudine (LdT) and tenofovir (TDF). Conventional or Peg-IFN alfa monotherapy has a narrow range of efficacy, is associated with several adverse effects and is inconvenient because of frequent injections. Oral nucleot(s)ide analogues (NA) are better tolerated; but virologic response to NA is frequently not durable and prolonged treatment is associated with the emergence of drug-resistant HBV mutants. Although the best treatment choice for CHB is not clarified yet, certain therapeutic concepts could be derived from the experience of treating patients with chronic hepatitis C or human immunodeficiency virus (HIV) infection. A major advancement in treating hepatitis C or HIV infection has been the development of combination therapy. Combination therapy has ever been investigated in patients with CHB, but again the optimal strategy remains to be identified. Entecavir, a carbocyclic deoxyguanosine NA, is one of the most potent anti-HBV agents ever discovered. In addition, the 6-year drug resistance rate is 1.2% in selected lamivudine-naïve cohorts. Pegylated interferon alfa-2a possesses both antiviral and immunomodulatory effects. Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN alfa in around 30-44% of these patients. Whether the combination therapy using Peg-IFN alfa-2a plus ETV can achieve a long-term beneficial effect against ETV or Peg-IFN alfa-2a alone is not clarified. A prior single-arm pilot study suggested that similar combination therapy may be beneficial in patients with CHB. In this proposal, the investigators thus hypothesize that the efficacy by using combination therapy with Peg-IFN alfa-2a plus prolonged ETV is superior to that by using ETV or Peg-IFN alfa-2a alone in that Peg-IFN may restore host immunity against HBV and prolonged ETV can maximize viral suppression. The objective of this clinical trial is to evaluate the efficacy of the combination of Peg-IFN alfa-2a at a dose of 180 mcg administered subcutaneously per week and ETV 0.5 mg daily for 48 weeks followed by ETV 0.5 mg daily monotherapy for an additional 96 weeks versus ETV 0.5 mg daily monotherapy for 144 weeks or Peg-IFN alfa-2a 180 mcg per week for 48 weeks in patients with HBeAg-negative CHB. It will be an open-label, randomized, comparative, multi-center clinical trial. The recruited patients will be equally randomized into three treatment groups. Treatment-free follow-up period will be 48 weeks in both groups of patients. The primary parameter is the "Simultaneous achievement of HBsAg titer below 100 IU/ml and HBV DNA below 300 IU/ml at 144 weeks after start of treatment", by an intention-to-treat analysis. Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of years 1, 2 and 3. The investigators anticipate that the rate of HBsAg <100 IU/mL plus HBV DNA <300 IU/mL at 3 years of the study period will be 30% for patients receiving Peg-IFN therapy and increased to be 45% for patients receiving Peg-IFN plus entecavir therapy. With a 5% nominal significance level (two-sided), 163 patients per group under a 1:1:1 ratio will provide 80% power to detect a difference of 15% in treatment response rates between group I and III. Because this will be a 4-year study for each patient, the investigators thus anticipate that the dropout rate may be as high as 10%. Accordingly, a total of 540 (180x3) patients will be recruited, in order to account for a dropout rate of up to10%.
This is a prospective randomized, open-label, phase IV clinical trial to learn the effects, good and/or bad, of discontinuing or continuing nucleos(t)ide analogue (NA) treatment for 72 weeks in participants with chronic hepatitis B infection whose immune system is controlling the amount of virus levels in the blood for at least 12 months of NA therapy. About 66 adult men and women will participate in this study from University Health Network which includes the Toronto Western Hospital for about 72 weeks.
Currently, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleons(t)ide analogues. The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a (peg-IFNα-2a). Interferon is administered for a finite duration while nucleotide analogues are usually administered for many years. But among hepatitis B e antigen （HBeAg） positive patients with high serum hepatitis B virus DNA levels, the rates of virological response are poor. And antiviral drug resistance is a major limiting factor to the success of nucleotide analogue treatment. Therefore, combination therapy using peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy. However, the addition of lamivudine to peg-IFNα-2a therapy led to a greater decrease in serum HBV DNA levels during treatment but did not increase the rate of HBeAg sero¬conversion. Entecavir is a nucleoside analogue superior to lamivudine and adefovir in achieving higher virological response, histological improvement and normalisation of ALT. Moreover, Entecavir has a high genetic barrier with a very low incidence of drug resistance. This study is aimed to investigate the efficacy of combination or sequential therapy using peg-IFNα-2a and entecavir in HBeAg-positive chronic hepatitis B(CHB) patients.
The host immunity has been generally recognized as the main factors to determine the outcome of chronic hepatitis B virus (HBV) infection; however, previous studies have shown that HBV-specific T cell and B cell function are exhausted in chronic hepatitis B (CHB) patients. Recently, It is suggested that hepatitis B surface antigen (HBsAg) may play a key role in the immune tolerance or immune exhaustion. Anti-HBV immune responses are partially recovered when patients achieved hepatitis B e antigen (HBeAg) seroconversion during antiviral therapy, and can be nearly recovered during HBsAg seroconversion. However, it is still difficult to achieve the ideal terminal, HBsAg seroconversion. For this reason, immunotherapy would be helpful to enhance the anti-HBV immunity and acquire higher HBsAg seroconversion. Here, the investigators propose a hypothesis that hepatitis B immune globin (HBIG)+granulocyte-macrophage colony-stimulating factor (GM-CSF)+HBV vaccine can enhance anti-HBV immune responses and improve HBsAg seroconversion in CHB patients who has achieved HBeAg seroconversion using nucleoside analogues treatment.
Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). For the treatment of lamivudine resistance, adefovir has been widely used (Lok AS and McMahon B, 2009). However, switching to adefovir monotherapy was also reported to be at high risk of resistance, 25% at year 2 (Yeon JE et al, 2006). Recently, adding adefovir on lamivudine was shown to be superior to switching to adefovir monotherapy by decreasing the adefovir resistance (Rapti I et al, 2007, Lampertico P et al, 2007). However, combination of adefovir and lamivudine does not increase antiviral activity compared with adefovir monotherapy in patients with lamivudine resistance (Peters MG et al, 2004). As many patients are still viremic with the treatment of lamivudine and adefovir over 1 year, the investigators need more potent combination of the drugs. Telbivudine is a new nucleoside analogue with potent antiviral activity. The previous phase III study has shown the superiority of telbivudine over lamivudine in HBeAg positive and negative subjects (Lai CL et al, 2007). Therefore, telbivudine plus adefovir may be a better treatment option than lamivudine plus adefovir for the lamivudine-resistant chronic hepatitis B patients. No study assessing the efficacy of telbivudine plus adefovir has been conducted for these patients. The aim of this study is to evaluate the safety and efficacy of telbivudine plus adefovir compared with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patients at the end of 1 year follow-up,
In Korea, the number of suboptimal responders to rescue combination therapy is also increasing. As a matter of fact, according to the investigations in Korea, HBV DNA undetectability at 48 weeks of adefovir and lamivudine combination rescue therapy for patients with lamivudine resistance was reported to be only 32.4%, which suggested that the appropriate another rescue therapy might be urgently required. However, there is no promising oral antiviral agents to control these patients in Asia-Pacific region, where tenofovir is not widely available. Tenofovir has a higher potent antiviral efficacy and a negligible drug resistance rate. The switch from adefovir to tenofovir in patients who have insufficient hepatitis B virus (HBV) suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to increased viral suppression or more HBeAg loss/seroconversion. Here, the investigators aimed to conduct a randomized study on evaluating the antiviral efficacy, safety, and tolerability of switching from adefovir to tenofovir in chronic hepatitis B patients who have suboptimal response to adefovir-based combination rescue therapy due to nucleoside analogues Resistance (SATIS study).
According to published literature, treatment with pegylated interferon (Peg-IFN) is associated with end of treatment response in treatment naive patients with chronic hepatitis B (CHB). It has antiviral as well as anti-fibrotic properties and treatment with Peg-IFN results in improvement of liver histology and down regulation of progression to cirrhosis of liver. Peg-IFN is administered for a finite duration. The major limitation of Peg-IFN is that only 30-49% patients are benefited by this anti-viral drug. Another potent anti-viral drug, entecavir (ETV), on the other hand, reduces HBV replication in most patients, but causes improvement of liver histology in only 30%, possibly because of its lack of immune modulatory ability like Peg-IFN. Also, ETV treatment is associated with several complications like emergence of HBV mutant. The aim of this study is to assess whether the combination of these two 'unique' anti-viral drugs offer the best possible outcome to treatment-naïve CHB patients, in terms of treatment response (virological and biochemical), treatment cost and duration and adverse events.