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Study Comparing the Safety of Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir Before Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B

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ClinicalTrials.gov Identifier: NCT00307242
Recruitment Status : Completed
First Posted : March 27, 2006
Last Update Posted : December 9, 2014
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University

Tracking Information
First Submitted Date  ICMJE March 24, 2006
First Posted Date  ICMJE March 27, 2006
Last Update Posted Date December 9, 2014
Study Start Date  ICMJE May 2005
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2006)
  • Observe the proportion of patients with ALT elevations (> 10 x ULN) at any time over the course of the switch
  • Study serum HBV DNA levels over time
  • Study serum ALT levels over time
  • Study the proportion of patients with YMDD variants at entry
  • Study the safety during the switching period
Original Primary Outcome Measures  ICMJE
 (submitted: March 24, 2006)
  • Observe the proportion of patients with ALT elevations (>10x ULN) at any time over the course of the switch.
  • Study serum HBV DNA levels over time
  • Study serum ALT levels over time
  • Study the proportion of patients with YMDD variants at entry
  • Study the safety during the switching period
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Comparing the Safety of Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir Before Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B
Official Title  ICMJE A Single Center Open-Label, Randomized Study Comparing the Safety of Immediately Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir for 12 Weeks Before Instituting Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B
Brief Summary

In earlier clinical studies, when patients who have been on lamivudine (LAM) were switched to adefovir dipivoxil (ADV), some patients developed ALT flares with an elevation of ALT > 10 x the upper limits of normal (ULN).

There were no cases of hepatic decompensation with the flares, however. The transition methods were varied among physicians from no overlapping to overlapping for 1 to 3 months with LAM and ADV. There is still some uncertainty about the optimal approach to switching from LAM to ADV.

This study will compare the safety of directly switching to ADV to a protocolled switch after a period of overlap of 12 weeks. This will facilitate pro-active switching in patients on LAM and will also highlight genotypic resistance ahead of phenotypic resistance as a reason to switch patients. Data to date have only been presented as part of a controlled study in patients with clinically evident LAM-resistance. This study will enroll patients who still have serum hepatitis B virus (HBV) DNA suppression whilst receiving LAM.

Detailed Description

Chronic HBV infection is an important worldwide cause of morbidity, mortality and source of potential new infections. There are an estimated 350 million carriers of HBV in the world. In China, Southeast Asia and sub-Saharan Africa, as many as 10-15% of the population are chronically infected. In North America and Northern Europe, infection and carrier rates are much lower, usually below 1%. Intermediate carrier rates of 1-5% are found in Southern Europe (e.g., Italy, Greece and Spain), parts of South and Central America, the Middle East and Japan. Persistent infection develops in over 90% of perinatally infected children and in 3-10% of people who become infected after the age of 6 years. Worldwide, it has been estimated that more than one million people die annually due to HBV-related end stage diseases such as cirrhosis and hepatocellular carcinoma.

The goal of antiviral therapy for hepatitis B is to reduce a patient's risks for progressive liver disease through prolonged suppression or eradication of HBV infection and to arrest or ameliorate HBV-related liver damage.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis B
Intervention  ICMJE Drug: Adefovir Dipivoxil
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: March 24, 2006)
40
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males and females ≥ 18 years of age with chronic hepatitis B
  • Hepatitis B surface antigen (HBsAg)(+) for a minimum of 6 months prior to entry
  • Hepatitis B envelope antigen (HBeAg)(+) or (-) at baseline
  • Patients having previously received LAM for at least 24 weeks
  • Patients with compensated liver function (Child-Pugh score ≤ 6)

Exclusion Criteria:

  • Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol.
  • Received immunoglobulins, interferon or other immune or cytokine-based therapies with possible activity in hepatitis B disease within 6 months prior to study screening.
  • Organ or bone marrow transplant recipients.
  • Evidence of active liver disease due to other causes (e.g., Wilson's disease, hemochromatosis, autoimmune hepatitis, hepatitis C or hepatitis D co-infection)
  • Patients taking parenteral (intravenous or intramuscular or subcutaneous) or oral steroids, immuno-suppressant therapies or chemotherapeutic agents within 2 months of study screening or expected to receive these agents during the course of the study.
  • Previous participation in an investigational trial involving administration of any investigational compound within 2 months prior to the study screening or those who received anti-HBV therapy other than lamivudine within the previous 3 months (e.g. anabolic steroids, ketaconazole, itraconazole, isoniazid, rifampin, rifabutin, simvastatin, lovastatin)
  • Clinically relevant alcohol or drug use or history of alcohol or drug use considered by the investigator to be sufficient to hinder compliance with treatment, follow up procedures or evaluation of adverse events
  • Lactating females or females with a positive serum pregnancy test.
  • Females of childbearing potential (post-puberty) unwilling or unable to have pregnancy testing at any study visit
  • Therapy with nephrotoxic drugs (e.g. aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cisplatin pentamidine, tacrolimus, cyclosporine) or competitors of renal excretion (e.g. probenecid) within 2 months prior to study screening or the expectation that subject will receive these during the course of the study.
  • The use of antiviral therapy with agents demonstrating potential anti-HBV activity other than lamivudine within the previous 3 months (e.g. famciclovir, lobucavir, emtricitabine, DAPD, L-FMAU, entecavir, ganciclovir or others).
  • History of hypersensitivity to nucleoside and/or nucleotide analogues.
  • Clinical, ultrasonographic or radiologic evidence of hepatic mass suggestive of hepatocellular carcinoma.
  • Serum alphafetoprotein (AFP) > 50 ng/mL at the first screening visit. However, if the AFP level is > 50 ng/mL at the first screening visit, but has remained stable or decreased over the 6 months preceding the first screening visit, and if there is no radiologic or ultrasonic evidence of hepatic mass(es) suggestive of hepatocellular carcinoma, the patient will be allowed to enroll.
  • Inability to comply with study requirements.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00307242
Other Study ID Numbers  ICMJE 05U.164
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Jefferson University
Study Sponsor  ICMJE Thomas Jefferson University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Hie-Won Hann, M.D. Thomas Jefferson University
PRS Account Thomas Jefferson University
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP