Hepatitis B
Conditions
Keywords
Hepatitis B, Antiviral, Tubular dysfunction, Entecavir, Tenofovir
Brief summary
Nucleotide anti-viral analogues, including adefovir and TDF, have demonstrated kidney toxicity in HIV/HBV co-infected patients and HBV mono-infected European patients. Investigators suspected similar kidney proximal tubular injury can also occur in HBV mono infected Asian patients receiving TDF treatment.
Detailed description
The primary objective of this study is to evaluate the safety use of ETV and TDF after at least 144 weeks of treatment in terms of the effects of renal tubular function as determined by (1) 24 hours Urine phosphate (wasting is \>1200 mg daily); (2) 24 hours β2-microglobulinuria (NL β2-microglobulin level, \<1 mg daily); (3) fractional excretion of uric acid, and (4) fractional tubular reabsorption of phosphorus. The secondary objectives are to evaluate: 1. To evaluate compare the anti-viral effects of both TDF and ETV as determined the percentage of patient who achieve HBV DNA levels below 60 IU/mL (by quantitative HBV DNA PCR test with lowest level of detection at 60 IU/mL) and ALT normalization by routine biochemical test after 144 weeks of treatment. 2. Serological responses including percentage of patients with HBeAg loss or seroconversion and HBsAg loss or seroconversion with TDF and ETV treatment in Asian-American adults with CHB infection. 3. To evaluate the three-year (one year treatment before enrollment and two year treatment after enrollment) the percentage of patient with anti-HBV drug resistance of TDF and ETV, including genotypic mutations in Asian-American adults with CHB.
Interventions
DRUGTenofovir Disoproxil Fumarate
300mg, oral daily for two years
DRUGEntecavir
0.5mg oral daily for two years.
Sponsors
New Discovery LLC
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 18-70 year-old Asian-American male or female patients with HBeAg+ or HBeAg-CHB * On TDF or ETV mono-therapy for 12-24 months, not previously exposed to other oral HBV drugs, nor received any type of interferon treatment in the past 12 months * Be willing to participate * Continuation of HBV treatment is medically indicated. That is for HBeAg-positive subjects, HBeAg remain positive or HBeAg becomes negative but still has detectable DNA by the PCR method; and for HBeAg-negative subjects, HBV DNA is either detectable or undetectable by the PCR method * No clinical or virologic evidence of anti-HBV resistance to TDF treatment at the time of entering tests * Serum creatinine \< 1.5 mg/L and estimated glomerular filtration rate (creatinine clearance) ≥ 60 mL/min/1.73m2 by the Cockcroft-Gault equation: (140-age in years)(body weight \[kg\] )/((72)(serum creatinine \[mg/dl\]) ) \[Note: multiply estimated rate 0. by 85 for women; use actual body weight\] * Adequate hematologic function (absolute neutrophil count ≥ 1,500/mm3; hemoglobin ≥ 10.0 g/dL) * To assure all the subjects will be regularly followed per study protocol and minimize the drop off rate, the subjects have to have documented pre-treatment full evaluation and necessary blood tests, medical adherence to HBV treatment, and regular follow-up (i.e., on HBV treatment not missing HBV medication (TDF or ETV) for more than a week, with medical follow-up for HBV treatment at least every 6 month and had all the necessary labs performed. * In the absence of
Exclusion criteria
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| renal tubular dysfunction | at 144 week after treatment with antiviral | renal tubular dysfunction as determined by (1) 24 hours Urine phosphate (wasting is \>1200 mg daily); (2) 24 hours β2-microglobulinuria (NL β2-microglobulin level, \<1 mg daily); (3) fractional excretion of uric acid, and (4) fractional tubular reabsorption of phosphorus. |
Countries
United States
Outcome results
None listed