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 (HBVSECURE)
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Hepatitis B Renal Failure With Tubular Necrosis |
Biological: plasma and urine samples, sample with ADN |
| Study Type: | Observational |
| Study Design: | Observational Model: Case Control Time Perspective: Prospective |
| 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. |
- the prevalence of "subclinical" proximal tubular abnormalities [ Time Frame: 2 years ] [ Designated as safety issue: No ]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.
- the prevalence at baseline of "subclinical" proximal tubular abnormalities [ Time Frame: 1 day ] [ Designated as safety issue: No ]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.
Biospecimen Retention: Samples With DNA
Plasma and urine samples for determination of TMPi / GFR and FEUA 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.
| Estimated Enrollment: | 700 |
| Study Start Date: | December 2011 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Groups/Cohorts | Assigned Interventions |
|---|---|
|
Patient naive
Patient with hepatitis B virus naive untreated
|
Biological: plasma and urine samples, sample with ADN
plasma and urine samples every three months Sample with ADN at baseline
|
|
Patient with TDF
Patient with hepatits B treated with Tenofovir
|
Biological: plasma and urine samples, sample with ADN
plasma and urine samples every three months Sample with ADN at baseline
|
|
Patient with ETV
Patient with hepatitis B virus treated with Entecavir
|
Biological: plasma and urine samples, sample with ADN
plasma and urine samples every three months Sample with ADN at baseline
|
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).
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Patient with hepatitis B virus
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Contacts and Locations| Contact: Véronique LOUSTAUD-RATTI, MD | 05 55 05 66 84 | veronique.loustaud-ratti@unilim.fr |
| France | |
| CHU d'Amiens | Recruiting |
| Amiens, France, 80054 | |
| Contact: Eric NGUYEN-KHAC, MD | |
| Principal Investigator: Eric NGUYEN-KHAC, MD | |
| CHU d'Angers | Recruiting |
| Angers, France, 49933 | |
| Contact: Isabelle FOUCHARD-HUBERT, MD | |
| Principal Investigator: Isabelle FOUCHARD-HUBERT, MD | |
| CHU de Besancon | Recruiting |
| Besancon, France, 25000 | |
| Contact: Vincent DI MARTINO, MD | |
| Principal Investigator: Vincent DI MARTINO, MD | |
| CHU de Bordeaux - Hôpital Saint André | Recruiting |
| Bordeaux, France, 33000 | |
| Contact: Pierre Henri BERNARD, MD | |
| Principal Investigator: Pierre Henri BERNARD, MD | |
| CHU de Brest | Not yet recruiting |
| Brest, France, 29609 | |
| Contact: Jean-Baptiste NOUSBAUM, MD | |
| Principal Investigator: Jean-Baptiste NOUSBAUM, MD | |
| CHU de CAEN | Recruiting |
| Caen, France, 14033 | |
| Contact: Thong DAO, MD | |
| Principal Investigator: Thong DAO, MD | |
| CHU de Clermont Ferrand | Recruiting |
| Clermont Ferrand, France, 63003 | |
| Contact: Armand ABERGEL, MD | |
| Principal Investigator: Armand ABERGEL, MD | |
| AP-HP - Hôpital Beaujon | Recruiting |
| Clichy, France, 92110 | |
| Contact: Patrick MARCELLIN, MD | |
| Principal Investigator: Patrick MARCELLIN, MD | |
| Centre Hospitalier Laennec de Creil | Not yet recruiting |
| Creil, France, 60109 | |
| Contact: Jean-Francois CADRANEL | |
| Principal Investigator: Jean Francois CADRANEL, MD | |
| Centre Hospitalier d'Hyères | Recruiting |
| Hyères, France, 83407 | |
| Contact: Christophe RENOU, MD | |
| Principal Investigator: Christophe RANOU, MD | |
| Centre Hospitalier de La Roche sur Yon | Recruiting |
| La Roche sur Yon, France, 85925 | |
| Contact: Matthieu SCHNEE, MD | |
| Principal Investigator: Matthieu SCHNEE, MD | |
| AP-HP - Hôpital Kremlin Bicêtre | Recruiting |
| Le Kremlin Bicêtre, France, 94275 | |
| Contact: Catherine BUFFET, MD | |
| Principal Investigator: Catherine BUFFET, MD | |
| CHU de Lille - Hôpital Huriet | Recruiting |
| Lille, France, 59037 | |
| Contact: Philippe MATHURIN, MD | |
| Principal Investigator: Philippe MATHURIN, M | |
| CHU de Limoges - Fédération Hépatologie | Recruiting |
| Limoges, France, 87042 | |
| Contact: Véronique LOUSTAUD-RATTI, MD | |
| Principal Investigator: Véronique LOUSTAUD-RATTI, MD | |
| Hospices Civils de Lyon - Hôpital Croix Rousse | Recruiting |
| Lyon, France, 69317 | |
| Contact: Christian TREPO, MD | |
| Principal Investigator: Christian TREPO, MD | |
| CHU de Montpellier - Hôpital Saint Eloi | Recruiting |
| Montpellier, France, 34295 | |
| Contact: Dominique LARREY, MD | |
| Principal Investigator: Dominique LARREY, MD | |
| CHU de Nice | Not yet recruiting |
| Nice, France, 06202 | |
| Contact: Albert TRAN, MD | |
| Principal Investigator: Albert TRAN, MD | |
| AP-HP - Hôpital Bichat | Recruiting |
| Paris, France, 75877 | |
| Contact: Xavier DUVAL, MD | |
| Principal Investigator: Xavier DUVAL, MD | |
| AP-HP - Hôpital La Pitié Salpétrière | Recruiting |
| Paris, France, 75651 | |
| Contact: Thierry POYNARD, MD | |
| Principal Investigator: Thierry POYNARD, MD | |
| CHU de Bordeaux - Hôpital Haut Levêque | Recruiting |
| Pessac, France, 33604 | |
| Contact: Victor de LEDINGHEN, MD | |
| Principal Investigator: Victor De LEDINGHEN, MD | |
| CHU de Point à Pitre | Not yet recruiting |
| Point à Pitre, France, 97159 | |
| Contact: Eric SAILLARD, MD | |
| Principal Investigator: Eric SAILLARD, MD | |
| CHU de Poitiers | Recruiting |
| Poitiers, France, 86021 | |
| Contact: Christine SILVAIN, MD | |
| Principal Investigator: Christine SILVAIN, MD | |
| CHU de Strasbourg - Hôpital Civil | Recruiting |
| Strasbourg, France, 67091 | |
| Contact: Michel DOFFOEL, MD | |
| Principal Investigator: Michel DOFFOEL, MD | |
| CHU de Tours - Hôpital Trousseau | Recruiting |
| Tours, France, 37044 | |
| Contact: Yannick BACQ, MD | |
| Principal Investigator: Yannick BACQ, MD | |
| CHU de Nancy - Hôpital Brabois | Recruiting |
| Vandoeuvre les Nancy, France, 54511 | |
| Contact: Jean Pierre BRONOWICKI, MD | |
| Principal Investigator: Jean Pierre BRONOWICKI, MD | |
More Information
No publications provided
| Responsible Party: | University Hospital, Limoges |
| ClinicalTrials.gov Identifier: | NCT01500265 History of Changes |
| Other Study ID Numbers: | I10006 HBVSECURE |
| Study First Received: | December 22, 2011 |
| Last Updated: | April 16, 2013 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
Keywords provided by University Hospital, Limoges:
|
hepatitis B virus early screening tools renal proximal tubular tolerance |
Additional relevant MeSH terms:
|
Hepatitis Hepatitis A Hepatitis B Necrosis Renal Insufficiency Kidney Cortex Necrosis Liver Diseases Digestive System Diseases Hepatitis, Viral, Human |
Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections DNA Virus Infections Pathologic Processes Kidney Diseases Urologic Diseases |
ClinicalTrials.gov processed this record on May 19, 2013