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

Sponsor

Guangdong Provincial People's Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT03062813

Collaborator

(none)

112

Enrollment

Location

Arms

37.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B Virus Associated Nephrotic Syndrome	Drug: Tacrolimus &entecavir Drug: placebo & entecavir	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

112 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

The Therapy of Tacrolimus Combined With Entecavir on HBV Associated Glomerulonephritis : A Multicenter, Prospective, Randomized, Controlled, Single-blind Trial.

Actual Study Start Date :

Feb 1, 2017

Anticipated Primary Completion Date :

Feb 1, 2020

Anticipated Study Completion Date :

Mar 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Tacrolimus &entecavir 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. Other Names: FK506,Prograf, baraclude
Active Comparator: 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.	Drug: placebo & entecavir 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. Other Names: baraclude

Arm

Intervention/Treatment

Experimental: 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.

Drug: Tacrolimus &entecavir

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.

Other Names:

FK506,Prograf, baraclude

Active Comparator: 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.

Drug: placebo & entecavir

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.

Other Names:

baraclude

Outcome Measures

Primary Outcome Measures

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

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)
Serum HBV DNA [25 weeks]
Serum HBV DNA was undetectable(HBV DNA<500copies/ml) at the end of 25 week-treatment.
The rate of acute kidney injury [25 weeks]
The number of patients who present acute kidney injury at the end of 25 week-treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Guangdong General Hospital, Guangdong Academy of Medical Sciences	Guangzhou	Guangdong	China	510080

Sponsors and Collaborators

Guangdong Provincial People's Hospital

Investigators

Study Chair: Zhiming Ye, PHD, Guangdong General Hospital, Guangdong Academy of Medical Sciences
Principal Investigator: 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
Study Director: Wei Shi, PHD, Guangdong General Hospital, Guangdong Academy of Medical Sciences