Ignite Creation Date:
2025-12-25 @ 12:38 AM
Ignite Modification Date:
2026-02-25 @ 10:05 PM
Study NCT ID:
NCT00531167
Status:
COMPLETED
Last Update Posted:
2012-10-22
First Post:
2007-09-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Adding Adefovir Dipivoxil Versus Switching to Entecavir in Patients With Lamivudine-resistant Chronic Hepatitis B
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'submissionInfos': [{'resetDate': '2013-04-17', 'releaseDate': '2013-03-03'}], 'estimatedResultsFirstSubmitDate': '2013-03-03'}}, 'conditionBrowseModule': {'meshes': [{'id': 'D019694', 'term': 'Hepatitis B, Chronic'}], 'ancestors': [{'id': 'D006509', 'term': 'Hepatitis B'}, {'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D018347', 'term': 'Hepadnaviridae Infections'}, {'id': 'D004266', 'term': 'DNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D006525', 'term': 'Hepatitis, Viral, Human'}, {'id': 'D006521', 'term': 'Hepatitis, Chronic'}, {'id': 'D006505', 'term': 'Hepatitis'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D019259', 'term': 'Lamivudine'}, {'id': 'C106812', 'term': 'adefovir dipivoxil'}, {'id': 'C413685', 'term': 'entecavir'}], 'ancestors': [{'id': 'D016047', 'term': 'Zalcitabine'}, {'id': 'D003841', 'term': 'Deoxycytidine'}, {'id': 'D003562', 'term': 'Cytidine'}, {'id': 'D011741', 'term': 'Pyrimidine Nucleosides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D003853', 'term': 'Deoxyribonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D015224', 'term': 'Dideoxynucleosides'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 219}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2012-10', 'completionDateStruct': {'date': '2012-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2012-10-18', 'studyFirstSubmitDate': '2007-09-17', 'studyFirstSubmitQcDate': '2007-09-17', 'lastUpdatePostDateStruct': {'date': '2012-10-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2007-09-18', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'PCR negativity (<60 IU/ml) of HBV DNA', 'timeFrame': 'At the end of year 2 (since starting rescue therapy for lamivudine resistance)'}], 'secondaryOutcomes': [{'measure': '1. PCR negativity (<60 IU/ml) of HBV DNA at year 1 (interim analysis) 2. Degrees of HBV DNA reduction 3. ALT normalization 4. HBeAg seroconversion 5. Development of resistant mutation 6. Virologic breakthrough 7. Biochemical breakthrough', 'timeFrame': 'At the end of year 2 except interim analysis'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['lamivudine resistant mutations', 'rescue therapy'], 'conditions': ['Chronic Hepatitis B']}, 'referencesModule': {'references': [{'pmid': '17256718', 'type': 'BACKGROUND', 'citation': 'Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. doi: 10.1002/hep.21513. No abstract available.'}, {'pmid': '17256746', 'type': 'BACKGROUND', 'citation': 'Rapti I, Dimou E, Mitsoula P, Hadziyannis SJ. Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B. Hepatology. 2007 Feb;45(2):307-13. doi: 10.1002/hep.21534.'}, {'pmid': '17178796', 'type': 'BACKGROUND', 'citation': 'Tenney DJ, Rose RE, Baldick CJ, Levine SM, Pokornowski KA, Walsh AW, Fang J, Yu CF, Zhang S, Mazzucco CE, Eggers B, Hsu M, Plym MJ, Poundstone P, Yang J, Colonno RJ. Two-year assessment of entecavir resistance in Lamivudine-refractory hepatitis B virus patients reveals different clinical outcomes depending on the resistance substitutions present. Antimicrob Agents Chemother. 2007 Mar;51(3):902-11. doi: 10.1128/AAC.00833-06. Epub 2006 Dec 18.'}, {'pmid': '14699491', 'type': 'BACKGROUND', 'citation': 'Peters MG, Hann Hw Hw, Martin P, Heathcote EJ, Buggisch P, Rubin R, Bourliere M, Kowdley K, Trepo C, Gray Df Df, Sullivan M, Kleber K, Ebrahimi R, Xiong S, Brosgart CL. Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology. 2004 Jan;126(1):91-101. doi: 10.1053/j.gastro.2003.10.051.'}]}, 'descriptionModule': {'briefSummary': 'Antiviral resistance mutations limit the efficacy of therapy for chronic hepatitis B. At year 2, resistance to adefovir may occur as high as 25% in patients with history of lamivudine resistance. Resistance to entecavir is reported to be 10% in lamivudine refractory patients during the same period. However, combination of lamivudine and adefovir decreased the adefovir resistance rate as low as 0% in the recent studies. By overcoming the antiviral resistance, the efficacy of therapy will be maximized. This study is intended to compare the efficacy of two strategies, combination of lamivudine and adefovir vs. entecavir monotherapy in patients with lamivudine resistance.', 'detailedDescription': "Recently, published data showed combination of lamivudine and adefovir lead to PCR negativity (\\<1000 copies/mL) up to 80% in the treatment of lamivudine-resistant chronic hepatitis B at year 2 \\[Rapti et al. Hepatology 2007 Feb;45(2):307-13.\\]. Other studies also showed 76% and 69% PCR negativity in mostly HBeAg negative subjects \\[Lampertico et al. Hepatology 2006 Oct;44(4) Suppl 1:556A-557A, Lampertico et al. Hepatology 2006 Oct;44(4) Suppl 1:693A-694A\\].\n\nIn the study for the treatment of lamivudine-resistant chronic hepatitis B patients which included HBeAg positive subjects more predominantly, entecavir monotherapy showed 34% of PCR negativity (\\<300 copies/mL) at year 2 \\[Tenney DJ, et al. Antimicrob Agents Chemother. 2007 Mar;51(3):902-11\\].\n\nAlthough it is assumed that combination of lamivudine and adefovir would be more effective than entecavir monotherapy for lamivudine resistant patients, we cannot verify the assumption, because there is no data directly comparing these two strategies until now.\n\nThe aim of this study is to determine the most effective therapy for the patients with lamivudine resistant chronic hepatitis B. We will compare the PCR negativity (\\<60 IU/ml) of HBV DNA at year 2 in patients receiving 'the combination of lamivudine and adefovir' and 'entecavir monotherapy'.\n\nSince we are planning to include lamivudine-resistant chronic hepatitis B patients regardless of HBeAg status, we assumed the PCR negativity (\\<300 copies/mL or \\<60 IU/mL) in adefovir-lamivudine combination and entecavir monotherapy group as 55% and 34%, respectively, considering HBeAg status and lower detection limit of PCR.\n\nThe result of this study will be able to clearly demonstrate the superiority of combination therapy with lamivudine and adefovir to entecavir monotherapy, which provide us the guide to rescue therapy for patients with lamivudine resistant HBV."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '16 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Chronic hepatitis B patients (positive HBsAg \\> 6 months)\n2. Age \\> 16 year old\n3. Serum alanine aminotransferase (ALT) \\>1.5 x ULN\n4. History of treatment with lamivudine more than 6 months\n5. Proven lamivudine resistant mutation\n6. HBV DNA level\\> 20000 IU/mL\n7. Compensated liver disease (Child-Pugh-Turcotte score over 7; prothrombin time prolonged more than 3 sec above ULN or INR over 1.5; serum albumin \\>3 g/dL; total bilirubin \\<2.5 mg/dL; No history of variceal bleeding, ascites, or hepatic encephalopathy)\n8. Patients willing to give informed consent\n\nExclusion Criteria:\n\n1. Out of inclusion criteria\n2. Any one of following\n\n * Serum phosphorus level under 2.4 mg/dL\n * Serum creatinine level over 1.5 mg/dL or creatinine clearance \\<50 mL/min\n * Absolute neutrophil count lower than 1000 cell/mL\n * Hb level under 10 g/dL (male), under 9 g/dL (female)\n * Serum AFP \\>100 ng/mL\n3. History of treatment with interferon-a, thymosin-alfa 1, or nucleos(t)ide analogue other than lamivudine in 6 months of screening\n4. Recipient of organ transplantation\n5. Positive antibody test to HIV, HCV or HDV\n6. Pregnant or breast feeding women\n7. Patients with hepatocellular carcinoma or uncontrolled malignant disease\n8. Habitual alcohol drinker (\\>140 g/week for men, \\>70 g/week for women)'}, 'identificationModule': {'nctId': 'NCT00531167', 'briefTitle': 'Adding Adefovir Dipivoxil Versus Switching to Entecavir in Patients With Lamivudine-resistant Chronic Hepatitis B', 'organization': {'class': 'OTHER', 'fullName': 'Korea University'}, 'officialTitle': 'Prospective Randomized Study for the Comparison of Adding Adefovir Dipivoxil and Switching to Entecavir in Patients With Lamivudine-resistant Chronic Hepatitis B', 'orgStudyIdInfo': {'id': 'CRT 111098'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'A', 'description': 'combination therapy', 'interventionNames': ['Drug: combination of lamivudine+adefovir vs entecavir']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'B', 'description': 'entecavir', 'interventionNames': ['Drug: combination of lamivudine+adefovir vs entecavir']}], 'interventions': [{'name': 'combination of lamivudine+adefovir vs entecavir', 'type': 'DRUG', 'otherNames': ['Zeffix, Hepsera, Baraclude'], 'description': 'Lamivudine 100 mg/day, Adefovir 10 mg/day, Entecavir 0.5 mg/day', 'armGroupLabels': ['A', 'B']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Ansan', 'state': 'Gyeonggi-do', 'country': 'South Korea', 'facility': 'Korea University Ansan Hospital', 'geoPoint': {'lat': 37.21795, 'lon': 127.55845}}, {'city': 'Seoul', 'country': 'South Korea', 'facility': 'Korea University Anam Hospital', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}], 'overallOfficials': [{'name': 'Hyung Joon Yim, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Korea University'}, {'name': 'Eileen Yoon', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Korea University'}, {'name': 'Yeon Seok Seo, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Korea University'}, {'name': 'Soon Ho Um, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Korea University'}, {'name': 'Chang Wook Kim, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'The Catholic University of Korea'}, {'name': 'Chang Don Lee', 'role': 'STUDY_DIRECTOR', 'affiliation': 'The Catholic University of Korea'}, {'name': 'Sang Hoon Park, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Hallym University'}, {'name': 'Myung Seok Lee, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Hallym University'}, {'name': 'Choong Kee Park, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Hallym University'}, {'name': 'Hee Bok Chae, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Chungbuk National University'}, {'name': 'Moon young Kim, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Yonsei University'}, {'name': 'Soon Koo Baik, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Yonsei University'}, {'name': 'Ju Hyun Kim, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Gachon University Gil Medical Center'}, {'name': 'Yun Soo Kim, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Gachon University Gil Medical Center'}, {'name': 'Jung Il Lee, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Inha University'}, {'name': 'Jin Woo Lee, M.D', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Inha University'}, {'name': 'Sun Pyo Hong, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Genematrix Inc.'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Korea University', 'class': 'OTHER'}, 'collaborators': [{'name': 'GlaxoSmithKline', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'associate professor', 'investigatorFullName': 'Hyung Joon Yim', 'investigatorAffiliation': 'Korea University'}}}, 'annotationSection': {'annotationModule': {'unpostedAnnotation': {'unpostedEvents': [{'date': '2013-03-03', 'type': 'RELEASE'}, {'date': '2013-04-17', 'type': 'RESET'}], 'unpostedResponsibleParty': 'Hyung Joon Yim, associate professor, Korea University'}}}}