Effect of Telbivudine on Renal Function and Proteinuria in Patients With CHB & Chronic Renal Diseases

NCT02049736 | Withdrawn

• 1 other identifier: Telbivudine for CKD
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• change in estimated glomerular filtration rate

  every 3 months for 5 years

Secondary Outcomes (2)

• proteinuria

  every 3 months for 5 years

• HBV DNA level

  every 6 months for 5 years

Study Arms (1)

Telbivudine

EXPERIMENTAL

Drug: Telbivudine

Interventions

Telbivudine DRUG

Telbivudine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Cheng Suen Man Shook Hepatitis Center, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Related Publications (18)

• Coresh J, Byrd-Holt D, Astor BC, Briggs JP, Eggers PW, Lacher DA, Hostetter TH. Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol. 2005 Jan;16(1):180-8. doi: 10.1681/ASN.2004070539. Epub 2004 Nov 24.

  PMID: 15563563 BACKGROUND

• Chen J, Wildman RP, Gu D, Kusek JW, Spruill M, Reynolds K, Liu D, Hamm LL, Whelton PK, He J. Prevalence of decreased kidney function in Chinese adults aged 35 to 74 years. Kidney Int. 2005 Dec;68(6):2837-45. doi: 10.1111/j.1523-1755.2005.00757.x.

  PMID: 16316361 BACKGROUND

• Bhimma R, Coovadia HM. Hepatitis B virus-associated nephropathy. Am J Nephrol. 2004 Mar-Apr;24(2):198-211. doi: 10.1159/000077065. Epub 2004 Feb 25.

  PMID: 14988643 BACKGROUND

• Chacko EC, Surrun SK, Mubarack Sani TP, Pappachan JM. Chronic viral hepatitis and chronic kidney disease. Postgrad Med J. 2010 Aug;86(1018):486-92. doi: 10.1136/pgmj.2009.092775.

  PMID: 20709771 BACKGROUND

• Wong PN, Fung TT, Mak SK, Lo KY, Tong GM, Wong Y, Loo CK, Lam EK, Wong AK. Hepatitis B virus infection in dialysis patients. J Gastroenterol Hepatol. 2005 Nov;20(11):1641-51. doi: 10.1111/j.1440-1746.2005.03837.x.

  PMID: 16246180 BACKGROUND

• London WT, Drew JS, Lustbader ED, Werner BG, Blumberg BS. Host responses to hepatitis B infection in patients in a chronic hemodialysis unit. Kidney Int. 1977 Jul;12(1):51-8. doi: 10.1038/ki.1977.78.

  PMID: 894916 BACKGROUND

• Peters MG. Special populations with hepatitis B virus infection. Hepatology. 2009 May;49(5 Suppl):S146-55. doi: 10.1002/hep.22965.

  PMID: 19399810 BACKGROUND

• Girndt M, Kohler H. Hepatitis B virus infection in hemodialysis patients. Semin Nephrol. 2002 Jul;22(4):340-50.

  PMID: 12118399 BACKGROUND

• Fabrizi F, Messa P, Basile C, Martin P. Hepatic disorders in chronic kidney disease. Nat Rev Nephrol. 2010 Jul;6(7):395-403. doi: 10.1038/nrneph.2010.37. Epub 2010 Apr 13.

  PMID: 20386560 BACKGROUND

• McKeage K, Keam SJ. Telbivudine: a review of its use in compensated chronic hepatitis B. Drugs. 2010 Oct 1;70(14):1857-83. doi: 10.2165/11204330-000000000-00000.

  PMID: 20836578 BACKGROUND

• But DY, Yuen MF, Fung J, Lai CL. Safety evaluation of telbivudine. Expert Opin Drug Saf. 2010 Sep;9(5):821-9. doi: 10.1517/14740338.2010.507190.

  PMID: 20662545 BACKGROUND

• Zhou XJ, Swan S, Smith WB, Marbury TC, Dubuc-Patrick G, Chao GC, Brown NA. Pharmacokinetics of telbivudine in subjects with various degrees of renal impairment. Antimicrob Agents Chemother. 2007 Dec;51(12):4231-5. doi: 10.1128/AAC.00557-07. Epub 2007 Sep 17.

  PMID: 17875994 BACKGROUND

• Lai CL, Gane E, Liaw YF, Hsu CW, Thongsawat S, Wang Y, Chen Y, Heathcote EJ, Rasenack J, Bzowej N, Naoumov NV, Di Bisceglie AM, Zeuzem S, Moon YM, Goodman Z, Chao G, Constance BF, Brown NA; Globe Study Group. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 2007 Dec 20;357(25):2576-88. doi: 10.1056/NEJMoa066422.

  PMID: 18094378 BACKGROUND

• Gane EJ, Wang Y, Liaw YF, Hou J, Thongsawat S, Wan M, Moon YM, Jia J, Chao YC, Niu J, Leung N, Samuel D, Hsu CW, Bao W, Lopez P, Avila C. Efficacy and safety of prolonged 3-year telbivudine treatment in patients with chronic hepatitis B. Liver Int. 2011 May;31(5):676-84. doi: 10.1111/j.1478-3231.2011.02490.x. Epub 2011 Mar 16.

  PMID: 21457439 BACKGROUND

• Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999 Mar 16;130(6):461-70. doi: 10.7326/0003-4819-130-6-199903160-00002.

  PMID: 10075613 BACKGROUND

• Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006.

  PMID: 19414839 BACKGROUND

• Szeto CC, Chow KM, Kwan BC, Chung KY, Leung CB, Li PK. Oral calcitriol for the treatment of persistent proteinuria in immunoglobulin A nephropathy: an uncontrolled trial. Am J Kidney Dis. 2008 May;51(5):724-31. doi: 10.1053/j.ajkd.2007.12.038. Epub 2008 Apr 3.

  PMID: 18436082 BACKGROUND

• Grubb A, Nyman U, Bjork J, Lindstrom V, Rippe B, Sterner G, Christensson A. Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan-Barratt prediction equations for children. Clin Chem. 2005 Aug;51(8):1420-31. doi: 10.1373/clinchem.2005.051557. Epub 2005 Jun 16.

  PMID: 15961546 BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Telbivudine

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 28, 2014
• First Posted: January 30, 2014
• Study Start: December 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: July 28, 2016

Record last verified: 2016-07

Locations

HK (1)