Hepatitis BHBVSECURENCT01500265
Assessment and Monitoring of Renal Proximal Tubular Tolerance of Nucleoside and Nucleotide Analogues Using Early Screening Tools in Patients Chronically Mono-infected With Hepatitis B Virus
An observational study of Hepatitis B and Renal Failure With Tubular Necrosis, run by University Hospital, Limoges at 25 sites in France.
Trial summary
Nucleotide analogues are associated in the long term with a risk of proximal tubular nephropathy (PT) with loss of phosphate, and, when compensatory mechanisms are overwhelmed, with osteopenia or osteoporosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis B, Renal Failure With Tubular Necrosis
- What is being tested?
- plasma and urine samples, sample with ADN
- How many people
- 216 participants
- Where
- 25 sitesFrance
- Study dates
- Dec 2011to Dec 2015
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patient with hepatitis B virus
Who may be able to join
- Age ≥ 18 years
- Patients with chronic HBV virus monoinfected
- For groups of patients treated: Patients with an indication of ETV or TDF
- For the group of naive patients: treatment-naive patients who have no indication of treatment (or do not want) for the duration of the study
- globular filtration rate (GFR) ≥ 50 ml / min / 1.73 m2 with no known cause of renal disease
- Patients who have given their informed and written informed consent
- Women of childbearing potential with an effective method of contraception without interruption for the duration of the research and during the 4 months after stopping treatment
Who cannot join
- Patients co-infected with HIV, hepatitis C or hepatitis Delta
- Patients who have already received the TDF in the group to receive the TDF and having already received ETV in the group to receive ETV
- Patient with a GFR <50 ml / min / 1.73 m2 or with known causes of renal disease
- Patient with hypophosphatemia <0.48 mmol / l
- Patients with hepatocellular carcinoma (diagnosed or suspected)
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
France25 sites
CHU d'Amiens
Amiens, 80054
CHU d'Angers
Angers, 49933
CHU de Besancon
Besançon, 25000
CHU de Bordeaux - Hôpital Saint André
Bordeaux, 33000
CHU de Brest
Brest, 29609
CHU de CAEN
Caen, 14033
CHU de Clermont Ferrand
Clermont-Ferrand, 63003
AP-HP - Hôpital Beaujon
Clichy, 92110
Centre Hospitalier Laennec de Creil
Creil, 60109
Centre Hospitalier d'Hyères
Hyères, 83407
Centre Hospitalier de La Roche sur Yon
La Roche-sur-Yon, 85925
AP-HP - Hôpital Kremlin Bicêtre
Le Kremlin-Bicêtre, 94275
CHU de Lille - Hôpital Huriet
Lille, 59037
CHU de Limoges - Fédération Hépatologie
Limoges, 87042
Hospices Civils de Lyon - Hôpital Croix Rousse
Lyon, 69317
CHU de Montpellier - Hôpital Saint Eloi
Montpellier, 34295
CHU de Nice
Nice, 06202
AP-HP - Hôpital La Pitié Salpétrière
Paris, 75651
AP-HP - Hôpital Bichat
Paris, 75877
CHU de Bordeaux - Hôpital Haut Levêque
Pessac, 33604
CHU de Point à Pitre
Point À Pitre, 97159
CHU de Poitiers
Poitiers, 86021
CHU de Strasbourg - Hôpital Civil
Strasbourg, 67091
CHU de Tours - Hôpital Trousseau
Tours, 37044
CHU de Nancy - Hôpital Brabois
Vandœuvre-lès-Nancy, 54511
About this study
Official title: Assessment and Monitoring of Renal Proximal Tubular Tolerance of Nucleoside and Nucleotide Analogues Using Early Screening Tools in Patients Chronically Mono-infected With Hepatitis B Virus.
Nucleotide analogues are associated in the long term with a risk of proximal tubular nephropathy (PT) with loss of phosphate, and, when compensatory mechanisms are overwhelmed, with osteopenia or osteoporosis. This toxicity has been particularly documented for tenofovir (TDF) in HIV disease, but its prevalence varies widely in the literature and is mainly associated with comorbidities: on average this prevalence is 0.39% after 48 weeks with exceptional cases of Fanconi syndrome described. In HBV monoinfection after 60 months of treatment with TDF, an 11% decrease of creatinine clearance (CreatCl) is observed. A single study showed a significant increase in creatinine level with entecavir (ETV) therapy, a second-generation nucleoside, hitherto not described as nephrotoxic. Furthermore, if the direct renal toxic effect characteristic of HIV in the kidney is well known, the role of HBV is less clear. Thus, HBV treatment appears to have a renal protective effect. The monitoring tools recommended by the SPC, CreatCl and plasma phosphorus level are late markers of tubular damage. The threshold of phosphate tubular reabsorption (TmPi/GFR) and the fractional excretion of uric acid (FEUA) are unexpensive early screening tools. However, the long-term evolution of this subclinical tubular involvement in HBV monoinfection is not known.
Read the detailed description
260 naive untreated patients, 220 patients treated with TDF and 220 patients treated with ETV and consecutively recruited in this interventional study, will have at baseline and every three months, a determination of phosphorus, creatinine, uric acid in plasma and urine samples for determination of TMPi / GFR and FEUA, and an evaluation of urinary calcium level. Depending on local opportunities, every six months, a urine sample will be stored in a declared biological collection to perform β2-microglobuline and cystatin dosage. A 25-OHD3 and PTH dosage will be conducted annually. A sample of genomic DNA will be collected after informed consent of the patient from a saliva sample (Saliva autocollection kits) in order to investigate genetic polymorphism in transporters responsible for the renal elimination of TDF and ETV. A serum sample will be stored at baseline, at one year and at endpoint for the retrospective dosage of bone markers (bone PAlk, PINP and CTX).
- Conditions
- Hepatitis B, Renal Failure With Tubular Necrosis
- Being tested
- plasma and urine samples, sample with ADN
- Keywords
- hepatitis B virus, early screening tools, renal proximal tubular tolerance
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
plasma and urine samples, sample with ADNBiological
plasma and urine samples every three months Sample with ADN at baseline
| Study group | Role | What they receive |
|---|---|---|
| Patient naive | Patient with hepatitis B virus naive untreated Receives: Biological: plasma and urine samples, sample with ADN | |
| Patient with TDF | Patient with hepatits B treated with Tenofovir Receives: Biological: plasma and urine samples, sample with ADN | |
| Patient with ETV | Patient with hepatitis B virus treated with Entecavir Receives: Biological: plasma and urine samples, sample with ADN |
What is being measured
The primary outcome is the main question the study is designed to answer.
the prevalence of "subclinical" proximal tubular abnormalities
to compare at 2 years the prevalence of "subclinical" proximal tubular abnormalities (TmPi/GFR and FEUA) in 3 groups of HBV monoinfected patients treated with TDF, ETV or untreated.
Measured: 2 years
Secondary outcomes (1)
the prevalence at baseline of "subclinical" proximal tubular abnormalities
to describe the prevalence at baseline, and the cumulative incidence of these abnormalities during the follow-up and determine the proportion of patients who present at 2 years an impaired CreatCl, an hypophosphatemia and an hypercalciuria (suggesting a bone impact), according to the presence or absence of "subclinical" proximal tubular abnormalities.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionDec 2013
- Study completionDec 2015
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.
- More trials run by University Hospital, LimogesThe sponsor's other registered studies.
- 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
- 216 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01500265
- Sponsor's protocol ID
- I10006 HBVSECURE
- Acronym
- HBVSECURE
- Status last verified
- Feb 2016
- First submitted
- 22 Dec 2011
- Last updated
- 24 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment and Monitoring of Renal Proximal Tubular Tolerance of Nucleoside and Nucleotide Analogues Using Early Screening Tools in Patients Chronically Mono-infected With Hepatitis B Virus.
- ClinicalTrials.gov ID
- NCT01500265
- Acronym / sponsor ID
- HBVSECURE / I10006 HBVSECURE
- Conditions
- Hepatitis B, Renal Failure With Tubular Necrosis
- Keywords
- hepatitis B virus, early screening tools, renal proximal tubular tolerance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 216 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- Dec 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 28 Dec 2011 (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 analogues are associated in the long term with a risk of proximal tubular nephropathy (PT) with loss of phosphate, and, when compensatory mechanisms are overwhelmed, with osteopenia or osteoporosis. This toxicity has been particularly documented for tenofovir (TDF) in HIV disease, but its prevalence varies widely in the literature and is mainly associated with comorbidities: on average this prevalence is 0.39% after 48 weeks with exceptional cases of Fanconi syndrome described. In HBV monoinfection after 60 months of treatment with TDF, an 11% decrease of creatinine clearance (CreatCl) is observed. A single study showed a significant increase in creatinine level with entecavir (ETV) therapy, a second-generation nucleoside, hitherto not described as nephrotoxic. Furthermore, if the direct renal toxic effect characteristic of HIV in the kidney is well known, the role of HBV is less clear. Thus, HBV treatment appears to have a renal protective effect. The monitoring tools recommended by the SPC, CreatCl and plasma phosphorus level are late markers of tubular damage. The threshold of phosphate tubular reabsorption (TmPi/GFR) and the fractional excretion of uric acid (FEUA) are unexpensive early screening tools. However, the long-term evolution of this subclinical tubular involvement in HBV monoinfection is not known.
Detailed description
260 naive untreated patients, 220 patients treated with TDF and 220 patients treated with ETV and consecutively recruited in this interventional study, will have at baseline and every three months, a determination of phosphorus, creatinine, uric acid in plasma and urine samples for determination of TMPi / GFR and FEUA, and an evaluation of urinary calcium level. Depending on local opportunities, every six months, a urine sample will be stored in a declared biological collection to perform β2-microglobuline and cystatin dosage. A 25-OHD3 and PTH dosage will be conducted annually. A sample of genomic DNA will be collected after informed consent of the patient from a saliva sample (Saliva autocollection kits) in order to investigate genetic polymorphism in transporters responsible for the renal elimination of TDF and ETV. A serum sample will be stored at baseline, at one year and at endpoint for the retrospective dosage of bone markers (bone PAlk, PINP and CTX).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patient naive | – | Biological: plasma and urine samples, sample with ADNPatient with hepatitis B virus naive untreated |
| Patient with TDF | – | Biological: plasma and urine samples, sample with ADNPatient with hepatits B treated with Tenofovir |
| Patient with ETV | – | Biological: plasma and urine samples, sample with ADNPatient with hepatitis B virus treated with Entecavir |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient with hepatitis B virus
Key inclusion criteria (7 listed)
- Age ≥ 18 years
- Patients with chronic HBV virus monoinfected
- For groups of patients treated: Patients with an indication of ETV or TDF
- For the group of naive patients: treatment-naive patients who have no indication of treatment (or do not want) for the duration of the study
- globular filtration rate (GFR) ≥ 50 ml / min / 1.73 m2 with no known cause of renal disease
Key exclusion criteria (5 listed)
- Patients co-infected with HIV, hepatitis C or hepatitis Delta
- Patients who have already received the TDF in the group to receive the TDF and having already received ETV in the group to receive ETV
- Patient with a GFR <50 ml / min / 1.73 m2 or with known causes of renal disease
- Patient with hypophosphatemia <0.48 mmol / l
- Patients with hepatocellular carcinoma (diagnosed or suspected)
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 |
|---|---|---|
| plasma and urine samples, sample with ADNplasma and urine samples every three months Sample with ADN at baseline | Biological | Patient naive, Patient with ETV, Patient with TDF |
Primary outcome
the prevalence of "subclinical" proximal tubular abnormalities
Time frame: 2 years
to compare at 2 years the prevalence of "subclinical" proximal tubular abnormalities (TmPi/GFR and FEUA) in 3 groups of HBV monoinfected patients treated with TDF, ETV or untreated.
1 secondary outcome
the prevalence at baseline of "subclinical" proximal tubular abnormalities
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2016.
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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.
The record lists no contact. Use the official record to reach the sponsor.
25 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 and Renal Failure With Tubular Necrosis, run by University Hospital, Limoges at 25 sites in France.
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 7 inclusion and 5 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: finished, as of the sponsor's last update on 24 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in France. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
the prevalence of "subclinical" proximal tubular abnormalities (time frame: 2 years). 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 24 Feb 2016; AzTrials last refreshed its copy on 8 Nov 2026.