Clinical trial NCT02049736: Effect of Telbivudine on Renal Function and Proteinuria in Patients With CHB & Chronic Renal Diseases
Official title: The Effect of Telbivudine on Renal Function and Proteinuria in Patients With Chronic Hepatitis B Infection and Chronic Kidney Diseases
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Chronic Hepatitis B
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2014-01-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Chronic kidney disease (CKD) and chronic viral hepatitis due to hepatitis B virus (HBV) are both major public health problems. Treatment of chronic HBV infection in CKD patients, however, is not well defined because of insufficient data from clinical trials. Telbivudine is a new antiviral that provides effective and sustained viral suppression in patients with compensated chronic hepatitis B infection. Unlike other nucleotide and nucleoside analogues, renal toxicity is uncommon in telbivudine, and dosage adjustment is not required in patients with mild renal impairment. We propose to conduct an open-label single-arm study to evaluate the effect of telbivudine on renal function and proteinuria in patients with chronic HBV infection and mild-to-moderate renal impairment. Twenty patients with chronic HBV infection and chronic kidney disease (estimated glomerular filtration rate 15 to 60 ml/min) will be recruited. They will be treated with telbivudine, with the dosage adjusted according to thei renal function, for 5 years. Serum HBV DNA, proteinuria, renal function, and urinary inflammatory markers will be monitored.

Detailed description: Chronic kidney disease (CKD) is a major public health problem worldwide over the past few decades, partly because of the increasing prevalence of hypertension, diabetes mellitus, and elderly individuals in most countries. In southeast Asia, chronic viral hepatitis due to hepatitis B virus (HBV) also poses significant morbidity and mortality \[2\]. Chronic HBV infection can cause chronic glomerulonephritis and CKD. More importantly, patients with CKD, irrespective to the underlying renal diagnosis, who acquire HBV infection have higher morbidity and mortality rates, and the management of chronic HBV infections among CKD patients with antiviral agents is associated with a high risk of adverse effects. The optimal management of CKD associated with chronic HBV infection is not well defined because of insufficient data from clinical trials.

Telbivudine (Sebivo®; Tyzeka®) is a synthetic nucleoside analogue that inhibits replication of HBV. Telbivudine is a potent antiviral that provides effective and sustained viral suppression in patients with compensated chronic hepatitis B infection, and is used in the treatment of adults with chronic hepatitis B with evidence of viral replication and persistently elevated serum transaminase levels, or histological evidence of active disease. Unlike most of the other nucleoside and nucleotide analogues, renal toxicity of telbivudine is uncommon, and dose adjustment is only necessary for patients with moderate to severe renal impairment. Recent data further suggest that telbivudine treatment may have a beneficial effect on renal function.

Eligibility criteria: Inclusion Criteria:

* aged 18-70 years
* hepatitis B surface antigen (HBsAg) positive
* clinical indication for antiviral therapy according to the Asian Pacific guideline \[16\]
* HBeAg positive, ALT \>2 times upper limit of normal AND HBV DNA \>20,000 IU/ml AND HBV DNA \<9 log10 copies/mL; OR
* HBeAg negative, ALT \>2 times upper limit of normal AND HBV DNA \>2,000 IU/ml AND HBV DNA \<7 log10 copies/mL; OR
* Evidence of advanced liver fibrosis or liver cirrhosis AND detectable HBV DNA
* estimated glomerular filtration rate (GFR) 15 to 60 ml/min/1.73m2
* willingness to give written consent and comply with the study protocol

Exclusion Criteria:

* Pregnancy, lactating or childbearing potential without effective method of birth control
* Severe gastrointestinal disorders that interfere with their ability to receive or absorb oral medication
* History of malignancy, including leukemia and lymphoma within the past 2 years
* Active systemic infection.
* Any other severe coexisting disease such as, but not limited to, advanced liver cirrhosis, myocardial infarction, cerebrovascular accident, malignant hypertension
* History of drug or alcohol abuse within past 2 years
* Patients receiving antiviral therapy for chronic hepatitis B within the past 12 months
* Patients receiving treatment of corticosteroid or other immunosuppressive / cytotoxic agents
* On other investigational drugs within last 3 months
* History of a psychological illness or condition such as to interfere with the patient's ability to understand the requirement of the study
* History of non-compliance
* Known history of sensitivity or allergy to telbivudine

Primary outcomes:
measure: change in estimated glomerular filtration rate
timeFrame: every 3 months for 5 years
Secondary outcomes:
measure: proteinuria
timeFrame: every 3 months for 5 years
measure: HBV DNA level
timeFrame: every 6 months for 5 years
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Cheng Suen Man Shook Hepatitis Center, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital
Study officials:
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