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This study was to evaluate the efficacy and safety of Tacrolimus combined with entecavir antiviral therapy for HBV-associated glomerulonephritis in china. Tacrolimus combined with entecavir rapidly and effectively induced remission of HBV-GN in Chinese adults. Meanwhile, Tacrolimus may have a synergistic antiviral effect with entecavir. The study protocol was reviewed and approved by Guangdong General Hospital's Ethic Committee, and all participants provided written informed consents. The study will be a prospective, randomized,controlled,single-blind, multi-centre, withdrawal study conducted by Guangdong general hospital, Guangdong Academy of Medical Sciences.there will be two phases, phase 1, Screening and enrolling 112 HBV-GN patients about one year,and phase 2, ongoing follow-up for 24 weeks.The data of all patients will be recorded in the HBV-GN electronic database.Before the randomisation, All patients will receive entecavir routine antiviral therapy for two weeks.And then they will be randomized to two different group,the treatment group: Tacrolimus combined with entecavir antiviral therapy,the control group: The Tacrolimus placebo and entecavir antiviral therapy. The Tacrolimus target trough concentration was 5-10 ng/mL during the therapy. The primary outcome variables were the number of patients who reached complete or partial remission (CR or PR) after the 25 week-treatment. CR was defined as <0.3 g/24 h proteinuria (UPCR<300mg/g.cr) or lower plus stable renal function (eGFR>50 ml/min/1.73 m2) and PR as proteinuria 0.3-3.0 g/24 h (UPCR 300-3000mg/g.cr) and 50% lower than baseline proteinuria plus stable renal function. Secondary outcome variables: 1) The number of patients who reached complete or partial remission (CR or PR) after the 13 week-treatment. 2) Serum creatinine (SCr) increased 2 times the baseline levels or 50% lower than the baseline eGFR(according to chronic kidney disease-EPI (CKD-EPI) )after the 25 week-treatment. 3)Serum HBV DNA was undetectable(HBV DNA<500copies/ml) at the end of 25 week-treatment. 4) The number of patients who present acute kidney injury at the end of 25 week-treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tacrolimus & entecavir | Experimental | Tacrolimus capsule, 0.5mg/capsule,1.0mg/capsule, 0.05-0.1mg/kg.d by mouth , every 12 hours for a day.Entecavir 0.5mg tablet by mouth every night. |
|
| placebo & entecavir | Active Comparator | Tacrolimus capsule, 0.5mg/capsule,1.0mg/capsule, 0.05-0.1mg/kg.d by mouth , every 12 hours for a day.Entecavir 0.5mg tablet by mouth every night. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus &entecavir | Drug | HBV-GN patients with nephrotic syndrome were randomly givenTacrolimus (0.05-0.1 mg/kg/day) combined with entecavir. Tacrolimus was divided into two daily doses at 12-hour intervals. Subsequent doses were adjusted to achieve a whole blood 12-hour trough level between 5 and 10 ng/ml.All patients will receive entecavir antiviral therapy(0.5mg/d), entecavir was taken once a day. All of HBV-GN patients were followed up to 25week. |
| Measure | Description | Time Frame |
|---|---|---|
| Remission rate of proteinuria | the number of patients who reached complete or partial remission (CR or PR) after the 25 week-treatment. CR was defined as <0.3 g/24 h proteinuria (UPCR<300mg/g.cr) or lower plus stable renal function (eGFR>50 ml/min/1.73 m2) and PR as proteinuria 0.3-3.0 g/24 h (UPCR 300-3000mg/g.cr) and 50% lower than baseline proteinuria plus stable renal function. | 25 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Remission rate of proteinuria | The number of patients who reached complete or partial remission (CR or PR) after the 13 week-treatment. | 13 weeks |
| The change of Scr | SCr increased 2 times the baseline levels or 50% lower than the baseline eGFR(according to CKD-EPI) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhiming Ye, PHD | Contact | 86-13826161678 | 13826161678@139.com | |
| Lifen Wang, PHD | Contact | 86-18022392896 | 15010942109@139.com |
| Name | Affiliation | Role |
|---|---|---|
| Zhiming Ye, PHD | Guangdong General Hospital, Guangdong Academy of Medical Sciences | Study Chair |
| Lifen Wang, PHD | Guangdong General Hospital, Guangdong Academy of Medical Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Guangdong General Hospital, Guangdong Academy of Medical Sciences | Recruiting | Guangzhou | Guangdong | 510080 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 2023605 | Result | Lai KN, Li PK, Lui SF, Au TC, Tam JS, Tong KL, Lai FM. Membranous nephropathy related to hepatitis B virus in adults. N Engl J Med. 1991 May 23;324(21):1457-63. doi: 10.1056/NEJM199105233242103. | |
| 2142748 | Result | Venkataseshan VS, Lieberman K, Kim DU, Thung SN, Dikman S, D'Agati V, Susin M, Valderrama E, Gauthier B, Prakash A, et al. Hepatitis-B-associated glomerulonephritis: pathology, pathogenesis, and clinical course. Medicine (Baltimore). 1990 Jul;69(4):200-16. |
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| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D015433 | Glomerulonephritis, Membranous |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
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| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| C413685 | entecavir |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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|
|
| placebo & entecavir | Drug | HBV-GN patients with nephrotic syndrome were randomly givenTacrolimus placebo (0.05-0.1 mg/kg/day) combined with entecavir.Tacrolimus placebo was divided into two daily doses at 12-hour intervals. All patients will receive entecavir antiviral therapy(0.5mg/d), entecavir was taken once a day. All of HBV-GN patients were followed up to 25week. |
|
|
| 25 weeks |
| Serum HBV DNA | Serum HBV DNA was undetectable(HBV DNA<500copies/ml) at the end of 25 week-treatment. | 25 weeks |
| The rate of acute kidney injury | The number of patients who present acute kidney injury at the end of 25 week-treatment. | 25 weeks |
| Lixia Xu, PHD | Guangdong General Hospital, Guangdong Academy of Medical Sciences | Principal Investigator |
| Xinling Liang, PHD | Guangdong General Hospital, Guangdong Academy of Medical Sciences | Principal Investigator |
| Wei Shi, PHD | Guangdong General Hospital, Guangdong Academy of Medical Sciences | Study Director |
| 21677438 | Result | Elewa U, Sandri AM, Kim WR, Fervenza FC. Treatment of hepatitis B virus-associated nephropathy. Nephron Clin Pract. 2011;119(1):c41-9; discussion c49. doi: 10.1159/000324652. Epub 2011 Jun 15. |
| 16164651 | Result | Tang S, Lai FM, Lui YH, Tang CS, Kung NN, Ho YW, Chan KW, Leung JC, Lai KN. Lamivudine in hepatitis B-associated membranous nephropathy. Kidney Int. 2005 Oct;68(4):1750-8. doi: 10.1111/j.1523-1755.2005.00591.x. |
| 24189358 | Result | Igarashi T, Shimizu A, Igarashi T, Hanaoka K, Yoshizaki K, Shigemori T, Shimizu S, Komeichi H, Itoh Y. Seroconversion of hepatitis B envelope antigen by entecavir in a child with hepatitis B virus-related membranous nephropathy. J Nippon Med Sch. 2013;80(5):387-95. doi: 10.1272/jnms.80.387. |
| 22371643 | Result | Zheng XY, Wei RB, Tang L, Li P, Zheng XD. Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis. World J Gastroenterol. 2012 Feb 28;18(8):821-32. doi: 10.3748/wjg.v18.i8.821. |
| 23150796 | Result | Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012 Nov 13;1:e00049. doi: 10.7554/eLife.00049. |
| 24375637 | Result | Watashi K, Sluder A, Daito T, Matsunaga S, Ryo A, Nagamori S, Iwamoto M, Nakajima S, Tsukuda S, Borroto-Esoda K, Sugiyama M, Tanaka Y, Kanai Y, Kusuhara H, Mizokami M, Wakita T. Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP). Hepatology. 2014 May;59(5):1726-37. doi: 10.1002/hep.26982. Epub 2014 Apr 1. |
| 20220333 | Result | Chen M, Li H, Li XY, Lu FM, Ni ZH, Xu FF, Li XW, Chen JH, Wang HY; Chinese Nephropathy Membranous Study Group. Tacrolimus combined with corticosteroids in treatment of nephrotic idiopathic membranous nephropathy: a multicenter randomized controlled trial. Am J Med Sci. 2010 Mar;339(3):233-8. doi: 10.1097/MAJ.0b013e3181ca3a7d. |
| 23449768 | Result | Chen Y, Schieppati A, Cai G, Chen X, Zamora J, Giuliano GA, Braun N, Perna A. Immunosuppression for membranous nephropathy: a systematic review and meta-analysis of 36 clinical trials. Clin J Am Soc Nephrol. 2013 May;8(5):787-96. doi: 10.2215/CJN.07570712. Epub 2013 Feb 28. |
| 23689577 | Result | Xu J, Zhang W, Xu Y, Shen P, Ren H, Wang W, Li X, Pan X, Chen N. Tacrolimus combined with corticosteroids in idiopathic membranous nephropathy: a randomized, prospective, controlled trial. Contrib Nephrol. 2013;181:152-62. doi: 10.1159/000348475. Epub 2013 May 8. |
| 17377504 | Result | Praga M, Barrio V, Juarez GF, Luno J; Grupo Espanol de Estudio de la Nefropatia Membranosa. Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial. Kidney Int. 2007 May;71(9):924-30. doi: 10.1038/sj.ki.5002215. Epub 2007 Mar 21. |
| 35672893 | Derived | Xie XF, Xie BY, Zhang WH, Hou JH, Liu DL, Zhang L, Xu LX, Li ZL, Li RZ, Ye ZM. The efficacy and safety of tacrolimus and entecavir combination therapy in the treatment of hepatitis B virus-associated glomerulonephritis: a multi-center, placebo controlled, and single-blind randomized trial. Ann Palliat Med. 2022 May;11(5):1762-1773. doi: 10.21037/apm-22-328. |
| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |