Tacrolimus Combined With Entecavir on HBV Associated Glomerulonephritis(HBV-GN)

NCT03062813 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: ZMYe
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatitis B Virus Associated Nephrotic Syndrome

Keywords

Hepatitis B virus, tacrolimus,membranous nephropathy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Remission rate of proteinuria

  13 weeks

• The change of Scr

  25 weeks

• Serum HBV DNA

  25 weeks

• The rate of acute kidney injury

  25 weeks

Study Arms (2)

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.

Drug: Tacrolimus &entecavir

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.

Drug: placebo & entecavir

Interventions

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.

Also known as: FK506,Prograf, baraclude

Tacrolimus & entecavir

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.

Also known as: baraclude

placebo & entecavir

Eligibility Criteria

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

You may qualify if:

• Male and female patients aged between 18 and 65 years with HBV-GN;
• All HBV-GN cases with biopsy-proven;
• Evidence of chronic HBV infection based on the presence of HBsAg, HBeAg or HBV DNA in the serum;(HBsAg, HBeAg was positive, HBV DNA ≥10\*3 IU/ml). Chronic HBV infection lasted for six months, and all patients did not receive the antiviral therapy in the past six months;
• Proteinuria more than 3.0g/24h, UPCR\>3000mg/g.cr, the result will be proofed by at least two tests;
• No glucocorticoid and immunosuppressive treatment within the previous 2 weeks.

You may not qualify if:

• The diagnosis of idiopathic membranous nephropathy(MN), systemic lupus erythematosus, malignancy, diabetes mellitus, severe infections or any other systemic disease known to be associated with secondary MN;
• eGFR\<30ml/min.1.73m\*2;
• Renal pathology showed that Tubular atrophy or Interstitial fibrosis was more than 50%;
• The participant is allergy to tacrolimus, entecavir;
• History of diabetes mellitus;
• History of severe heart disease or cerebrovascular diseases;
• Other active infection such as cytomegalovirus (CMV),Tuberculosis,Hepatitis A virus (HAV),Hepatitis C virus (HCV),Hepatitis D virus (HDV); Innate or acquired immunodeficiency; liver cirrhosis, liver malignment tumor;
• Pregnant, trying to become pregnant or breast feeding;

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

Study Sites (1)

Guangdong General Hospital, Guangdong Academy of Medical Sciences

Guangzhou, Guangdong, 510080, China

RECRUITING

Related Publications (13)

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  PMID: 24375637 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.

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• 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.

  PMID: 35672893 DERIVED

MeSH Terms

Conditions

Hepatitis B; Glomerulonephritis, Membranous

Interventions

Tacrolimus; 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; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• 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

• 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

Central Study Contacts

Zhiming Ye, PHD

CONTACT

86-13826161678; 13826161678@139.com

Lifen Wang, PHD

CONTACT

86-18022392896; 15010942109@139.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2017
• First Posted: February 23, 2017
• Study Start: February 1, 2017
• Primary Completion: February 1, 2020
• Study Completion: March 31, 2020
• Last Updated: February 24, 2017

Record last verified: 2017-02

Locations

CN (1)