Hepatitis B Virus Associated Nephrotic Syndrome Clinical Trial
— TOHBVGNOfficial title:
The Therapy of Tacrolimus Combined With Entecavir on HBV Associated Glomerulonephritis : A Multicenter, Prospective, Randomized, Controlled, Single-blind Trial.
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 deļ¬ned 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.
| Status | Recruiting |
| Enrollment | 112 |
| Est. completion date | March 31, 2020 |
| Est. primary completion date | February 1, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 65 Years |
| Eligibility |
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; |
| Country | Name | City | State |
|---|---|---|---|
| China | Guangdong General Hospital, Guangdong Academy of Medical Sciences | Guangzhou | Guangdong |
| Lead Sponsor | Collaborator |
|---|---|
| Guangdong General Hospital |
China,
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* Note: There are 12 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Remission rate of proteinuria | the number of patients who reached complete or partial remission (CR or PR) after the 25 week-treatment. CR was de?ned 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 | Remission rate of proteinuria | The number of patients who reached complete or partial remission (CR or PR) after the 13 week-treatment. | 13 weeks | |
| Secondary | The change of Scr | SCr increased 2 times the baseline levels or 50% lower than the baseline eGFR(according to CKD-EPI) | 25 weeks | |
| Secondary | Serum HBV DNA | Serum HBV DNA was undetectable(HBV DNA<500copies/ml) at the end of 25 week-treatment. | 25 weeks | |
| Secondary | The rate of acute kidney injury | The number of patients who present acute kidney injury at the end of 25 week-treatment. | 25 weeks |