Hepatitis B Virus (HBV) Viral Suppression by Entecavir in Adefovir Partial Responders

NCT00704106 | Completed

• 1 other identifier: PHF008
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 6

Brief Summary

We propose a largely retrospective study with short-term prospective follow-up in a subgroup of patients who have not yet been treated with 48 weeks of entecavir following partial response to adefovir. The aim of the study is to describe sequential virologic response to adefovir and entecavir.

Conditions

Hepatitis B

Keywords

Hepatitis B; HBV; Treatment

Outcome Measures

Primary Outcomes (1)

• HBV DNA PCR after 12 weeks of entecavir from the time of medication switching: percent of patients with <2log drop in HBV DNA and percent of patients with complete viral suppression during adefovir versus during entecavir.

  48 weeks or after

Secondary Outcomes (4)

• HBV DNA PCR after 24 weeks of entecavir from the time of medication switching.

  48 weeks or after

• HBV DNA PCR after 48 weeks of entecavir from the time of medication switching.

  48 weeks or after

• BR and CR at 24 and 48 weeks of therapy with entecavir.

  48 weeks or after.

• BR and CR for longer duration of therapy if available.

  48 weeks or after.

Study Arms (4)

Group 1

Persistent viremia after 48 weeks or longer.

Drug: Entecavir

Group 2

\<2 log IU/mL drop from initial HBVDNA after 12 weeks of adefovir

Drug: Entecavir

Group 3

Patients who responded to adefovir and were switched to entecavir.

Drug: Entecavir

Group 4

Patients with 160 copies/mL (100 IU/mL) or higher at the time of medication switch.

Drug: Entecavir

Interventions

Entecavir DRUG

0.5 or 1 mg dose qd

Also known as: Baraclude

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Age 18 years or older * All genders and ethnicity * Positive HBsAg * HBeAg positive and negative * Pretreatment HBV DNA of 10,000 copies/mL or higher (for purposes of this study, both copies and equivalent IU measurements will be recorded and analyzed) * Patients who are switched to, or prescribed, entecavir after treatment with adefovir for at least 12 weeks by the providing physician * Patients with and without prior lamivudine exposure will be enrolled but enrollment of lamivudine experienced cases will be limited to no more than 30 patients total

You may qualify if:

• Age 18 years or older
• All genders and ethnicity
• Positive HBsAg
• HBeAg positive and negative
• Pretreatment HBV DNA of 10,000 copies/mL or higher (for purposes of this study, both copies and equivalent IU measurements will be recorded and analyzed)
• Patients who are switched to, or prescribed, entecavir after treatment with adefovir for at least 12 weeks by the providing physician.
• Patients with and without prior lamivudine exposure will be enrolled but enrollment of lamivudine experienced cases will be limited to no more than 30 patients total

You may not qualify if:

• Patients who refused to consent to the study
• Patients younger than 18
• Vulnerable subjects such as pregnant women, prisoners, employees, patients with significant cognitive deficits.
• Patients with prior exposure to another nucleoside for more than 2 weeks. Those with prior exposure to lamivudine will be enrolled under conditions detailed above.
• HIV co-infection
• HCV co-infection
• HDV co-infection
• Recipients of solid organ transplantation
• Patients who receive high-dose steroid (60 mg/d or higher and for longer than 10 days)

Sponsors & Collaborators

• Pacific Health Foundation: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

San Jose Gastroenterology

San Jose, California, 95116, United States

Location

San Jose Gastroenterology

San Jose, California, 95128, United States

Location

Asian Village Medical Clinic

Chicago, Illinois, 60640, United States

Location

Houston Gastroenterology Clinic

Houston, Texas, 77072, United States

Location

Digestive Health Associates of Texas

Plano, Texas, 75093, United States

Location

Related Publications (15)

• McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25 Suppl 1:3-8. doi: 10.1055/s-2005-915644.

  PMID: 16103976 BACKGROUND

• Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.

  PMID: 16391218 BACKGROUND

• Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678-86. doi: 10.1053/j.gastro.2005.11.016.

  PMID: 16530509 BACKGROUND

• Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.

  PMID: 15470215 BACKGROUND

• Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. doi: 10.1002/hep.21513. No abstract available.

  PMID: 17256718 BACKGROUND

• Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H, Wright TL. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol. 2006 Aug;4(8):936-62. doi: 10.1016/j.cgh.2006.05.016. Epub 2006 Jul 14.

  PMID: 16844425 BACKGROUND

• Shaw T, Locarnini S. Entecavir for the treatment of chronic hepatitis B. Expert Rev Anti Infect Ther. 2004 Dec;2(6):853-71. doi: 10.1586/14789072.2.6.853.

  PMID: 15566330 BACKGROUND

• Chan HL, Heathcote EJ, Marcellin P, Lai CL, Cho M, Moon YM, Chao YC, Myers RP, Minuk GY, Jeffers L, Sievert W, Bzowej N, Harb G, Kaiser R, Qiao XJ, Brown NA; 018 Study Group. Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial. Ann Intern Med. 2007 Dec 4;147(11):745-54. doi: 10.7326/0003-4819-147-11-200712040-00183. Epub 2007 Oct 1.

  PMID: 17909201 BACKGROUND

• Keeffe EB, Zeuzem S, Koff RS, Dieterich DT, Esteban-Mur R, Gane EJ, Jacobson IM, Lim SG, Naoumov N, Marcellin P, Piratvisuth T, Zoulim F. Report of an international workshop: Roadmap for management of patients receiving oral therapy for chronic hepatitis B. Clin Gastroenterol Hepatol. 2007 Aug;5(8):890-7. doi: 10.1016/j.cgh.2007.05.004. Epub 2007 Jul 13.

  PMID: 17632041 BACKGROUND

• Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, Walsh A, Fang J, Hsu M, Mazzucco C, Eggers B, Zhang S, Plym M, Klesczewski K, Tenney DJ. Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology. 2006 Dec;44(6):1656-65. doi: 10.1002/hep.21422.

  PMID: 17133475 BACKGROUND

• Tenney DJ, Rose RE, Baldick CJ, Pokornowski KA, Eggers BJ, Fang J, Wichroski MJ, Xu D, Yang J, Wilber RB, Colonno RJ. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology. 2009 May;49(5):1503-14. doi: 10.1002/hep.22841.

  PMID: 19280622 BACKGROUND

• Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart CL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. 2005 Jun 30;352(26):2673-81. doi: 10.1056/NEJMoa042957.

  PMID: 15987916 BACKGROUND

• Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Brosgart CL, Borroto-Esoda K, Arterburn S, Chuck SL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006 Dec;131(6):1743-51. doi: 10.1053/j.gastro.2006.09.020. Epub 2006 Sep 20.

  PMID: 17087951 BACKGROUND

• Ha NB, Ha NB, Garcia RT, Trinh HN, Vu AA, Nguyen HA, Nguyen KK, Levitt BS, Nguyen MH. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Hepatology. 2009 Sep;50(3):727-34. doi: 10.1002/hep.23044.

  PMID: 19517525 BACKGROUND

• Nguyen NH, Trinh HN, Nguyen TT, Do ST, Tran P, Nguyen HA, Nguyen KK, Garcia RT, Lutchman GA, Nguyen MH. Safety and efficacy of entecavir in adefovir-experienced patients. J Gastroenterol Hepatol. 2015 Jan;30(1):43-50. doi: 10.1111/jgh.12728.

  PMID: 25168842 DERIVED

MeSH Terms

Conditions

Hepatitis B

Interventions

entecavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Huy N Trinh, M.D.

  Pacific Health Foundation

  PRINCIPAL INVESTIGATOR

• Mindie H Nguyen, M.D., M.A.S.

  Pacific Health Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2008
• First Posted: June 24, 2008
• Study Start: May 1, 2008
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: November 14, 2022

Record last verified: 2022-11

Locations

US (6)