Hepatitis BNCT01715987
Tubular Function in Asian-American Patients Receiving TDF or ETV for HBV Treatment
An observational study of Hepatitis B, run by New Discovery LLC at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Tenofovir Disoproxil Fumarate and Entecavir
- Type of treatment
- Pill or oral medicine
- How many people
- 48 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2012to May 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Asian Americans with hepatitis B taking Entecavir or Tenofovir.
Who may be able to join
- 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:
Show all 10Show fewer
- (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.
Who cannot join
- Ethnicity: Non-Asian CHB patients
- Age: >70 years old
- Body weight and height: BMI ≥ 30
- Concomitant nephrotoxic agents - record all prescription and nonprescription items including herbs and natural remedies, NSAIDs, acyclovir, statins, ACEI or ARBs, Valproate
- Any other antiretroviral meds, antibiotic exposure during study to be noted
- History of HCV, HDV, or HIV co-infection
Show all 35Show fewer
- Prior history of clinical hepatic decompensation defined as direct (conjugated) bilirubin ≥ 1.2 ULN; PT ≥ 1.2 ULN, platelets ≤ 50,000/mm3, or serum albumin ≤ 3.5 g/dL, ascites, jaundice, encephalopathy, or variceal hemorrhage
- Serum α-fetoprotein ≥ 50 ng/mL
- Evidence of hepatocellular carcinoma (HCC)
- History of solid organ or bone marrow transplantation
- History of malignancies in the past 5 years
- Pregnant women, and women who are breast feeding or who believe they may wish to become pregnant during the course of the study.
- Males and females of reproductive potential who are not willing to use an effective method of contraception during the study. For males, condoms should be used and for females, a barrier contraception method should be used in combination with one other form of contraception.
- History of significant renal disease
- History of significant bone disease
- History of HTN or DM on medical treatment
- Ongoing therapy with any of the following:
- Nephrotoxic agents
- Parenteral aminoglycoside antibiotics
- Cidofovir
- Cisplatin
- Foscarnet
- IV amphotericin B
- IV pentamidine
- Oral or IV ganciclovir
- Cyclosporine
- Tacrolimus
- IV vancomycin
- Chronic daily non-steroidal anti-inflammatory drug therapy
- Competitors of renal excretion Systemic chemotherapeutic agents
- Systemic corticosteroids
- Interleukin-2 (IL-2) and other immunomodulating agents
- Investigational agents (except with the expressed approval of the lead investigators) Administration of any of the above medications must be discontinued at least 30 days prior to the Baseline Visit and for the duration of the study period.
- Known hypersensitivity to the study drugs, the metabolites or formulation excipients
- Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigators, would make the subject unsuitable for the study or unable to comply with dosing requirements
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Asian Pacific Liver Center at St. Vincent Medical Center
Los Angeles, California, 90057
New Discovery LLC
New York, New York, 11355
About this study
Official title: A Prospective and Open-Label Study of the Effect on Proximal Tubular Function in Asian-American Patients Receiving Tenofovir Disoproxil Fumarate (TDF) or Entecavir (ETV) for HBV Treatment
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.
Read the 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:
- 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.
- 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.
- 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.
- Conditions
- Hepatitis B
- Being tested
- Tenofovir Disoproxil Fumarate, Entecavir
- Keywords
- Hepatitis B, Antiviral, Tubular dysfunction, Entecavir, Tenofovir
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir Disoproxil FumarateDrug
Also called Viread
300mg, oral daily for two years
EntecavirDrug
Also called Baraclude
0.5mg oral daily for two years.
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir Disoproxil Fumarate | Patients who are taking Tenofovir Disoproxil Fumarate. Receives: Drug: Tenofovir Disoproxil Fumarate | |
| Entecavir | Patients who are taking Entecavir. Receives: Drug: Entecavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
renal tubular dysfunction
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.
Measured: at 144 week after treatment with antiviral
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2012 (estimated)
- Study startOct 2012
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- New Discovery LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Calvin Q Pan, M.D., Principal investigator, Mount Sinai School of Medicine, New York
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01715987
- Sponsor's protocol ID
- BMS AI463-254
- Status last verified
- Jun 2015
- First submitted
- 23 Oct 2012
- Last updated
- 6 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective and Open-Label Study of the Effect on Proximal Tubular Function in Asian-American Patients Receiving Tenofovir Disoproxil Fumarate (TDF) or Entecavir (ETV) for HBV Treatment
- ClinicalTrials.gov ID
- NCT01715987
- Acronym / sponsor ID
- BMS AI463-254
- Conditions
- Hepatitis B
- Keywords
- Hepatitis B, Antiviral, Tubular dysfunction, Entecavir, Tenofovir
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 48 participants (actual)
- Lead sponsor
- New Discovery LLCIndustry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 29 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
- 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir Disoproxil Fumarate | – | Drug: Tenofovir Disoproxil FumaratePatients who are taking Tenofovir Disoproxil Fumarate. |
| Entecavir | – | Drug: EntecavirPatients who are taking Entecavir. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Asian Americans with hepatitis B taking Entecavir or Tenofovir.
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (35 listed)
- Ethnicity: Non-Asian CHB patients
- Age: >70 years old
- Body weight and height: BMI ≥ 30
- Concomitant nephrotoxic agents - record all prescription and nonprescription items including herbs and natural remedies, NSAIDs, acyclovir, statins, ACEI or ARBs, Valproate
- Any other antiretroviral meds, antibiotic exposure during study to be noted
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir Disoproxil FumarateAlso: Viread300mg, oral daily for two years | Drug | Tenofovir Disoproxil Fumarate |
| EntecavirAlso: Baraclude0.5mg oral daily for two years. | Drug | Entecavir |
Primary outcome
renal tubular dysfunction
Time frame: 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.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Calvin Q Pan, M.D. principal investigator
Mount Sinai School of Medicine, New York
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis B, run by New Discovery LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
renal tubular dysfunction (time frame: at 144 week after treatment with antiviral). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2017.