Clinical trial NCT03062813: Tacrolimus Combined With Entecavir on HBV Associated Glomerulonephritis(HBV-GN)
Official title: The Therapy of Tacrolimus Combined With Entecavir on HBV Associated Glomerulonephritis : A Multicenter, Prospective, Randomized, Controlled, Single-blind Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatitis B Virus Associated Nephrotic Syndrome
Keywords: Hepatitis B virus, tacrolimus,membranous nephropathy
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2017-02-23
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;

Primary outcomes:
measure: Remission rate of proteinuria
timeFrame: 25 weeks
Secondary outcomes:
measure: Remission rate of proteinuria
timeFrame: 13 weeks
measure: The change of Scr
timeFrame: 25 weeks
measure: Serum HBV DNA
timeFrame: 25 weeks
measure: The rate of acute kidney injury
timeFrame: 25 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong General Hospital, Guangdong Academy of Medical Sciences
state: Guangdong
Study officials:
affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences
name: Zhiming Ye, PHD
role: STUDY_CHAIR
affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences
name: Lifen Wang, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences
name: Lixia Xu, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences
name: Xinling Liang, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences
name: Wei Shi, PHD
role: STUDY_DIRECTOR
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