Hepatitis B Virus Associated Nephrotic Syndrome
Conditions
Keywords
Hepatitis B virus, tacrolimus,membranous nephropathy
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.
Interventions
DRUGTacrolimus &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.
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.
Sponsors
Guangdong Provincial People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactZhiming Ye, PHD
Backup ContactLifen Wang, PHD
Outcome results
None listed