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

Phase 4

• Conditions: Hepatitis B Virus Associated Nephrotic Syndrome
• Interventions: Drug: Tacrolimus &entecavir; Drug: placebo & entecavir

• Registration Number: NCT03062813
• Lead Sponsor: Guangdong Provincial People's Hospital

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2017-02
• Study Start: 2017-02-01
• Study First Submitted: 2017-02-20
• Study First Submitted QC: 2017-02-20
• Last Update Submitted: 2017-02-22
• Study First Posted: 2017-02-23
• Last Update Posted: 2017-02-24
• Primary Completion: 2020-02-01
• Study Completion: 2020-03-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 112

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.

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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;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tacrolimus & entecavir	Tacrolimus &entecavir	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	placebo & entecavir	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.

Primary Outcome Measures

Name	Time	Method
Remission rate of proteinuria	25 weeks	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 Measures

Name	Time	Method
Serum HBV DNA	25 weeks	Serum HBV DNA was undetectable(HBV DNA\<500copies/ml) at the end of 25 week-treatment.
Remission rate of proteinuria	13 weeks	The number of patients who reached complete or partial remission (CR or PR) after the 13 week-treatment.
The change of Scr	25 weeks	SCr increased 2 times the baseline levels or 50% lower than the baseline eGFR(according to CKD-EPI)
The rate of acute kidney injury	25 weeks	The number of patients who present acute kidney injury at the end of 25 week-treatment.

Trial Locations

Locations (1)

Guangdong General Hospital, Guangdong Academy of Medical Sciences; 🇨🇳 Guangzhou, Guangdong, China