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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Limoges
ClinicalTrials.gov Identifier:
NCT01500265
First received: December 22, 2011
Last updated: February 17, 2014
Last verified: February 2014
  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.

Resource links provided by NLM:


Further study details as provided by University Hospital, Limoges:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 216
Study Start Date: December 2011
Estimated Study Completion Date: December 2015
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
Study Population

Patient with hepatitis B virus

Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01500265

Locations
France
CHU d'Amiens
Amiens, France, 80054
CHU d'Angers
Angers, France, 49933
CHU de Besancon
Besancon, France, 25000
CHU de Bordeaux - Hôpital Saint André
Bordeaux, France, 33000
CHU de Brest
Brest, France, 29609
CHU de CAEN
Caen, France, 14033
CHU de Clermont Ferrand
Clermont Ferrand, France, 63003
AP-HP - Hôpital Beaujon
Clichy, France, 92110
Centre Hospitalier Laennec de Creil
Creil, France, 60109
Centre Hospitalier d'Hyères
Hyères, France, 83407
Centre Hospitalier de La Roche sur Yon
La Roche sur Yon, France, 85925
AP-HP - Hôpital Kremlin Bicêtre
Le Kremlin Bicêtre, France, 94275
CHU de Lille - Hôpital Huriet
Lille, France, 59037
CHU de Limoges - Fédération Hépatologie
Limoges, France, 87042
Hospices Civils de Lyon - Hôpital Croix Rousse
Lyon, France, 69317
CHU de Montpellier - Hôpital Saint Eloi
Montpellier, France, 34295
CHU de Nice
Nice, France, 06202
AP-HP - Hôpital Bichat
Paris, France, 75877
AP-HP - Hôpital La Pitié Salpétrière
Paris, France, 75651
CHU de Bordeaux - Hôpital Haut Levêque
Pessac, France, 33604
CHU de Point à Pitre
Point à Pitre, France, 97159
CHU de Poitiers
Poitiers, France, 86021
CHU de Strasbourg - Hôpital Civil
Strasbourg, France, 67091
CHU de Tours - Hôpital Trousseau
Tours, France, 37044
CHU de Nancy - Hôpital Brabois
Vandoeuvre les Nancy, France, 54511
Sponsors and Collaborators
University Hospital, Limoges
  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: February 17, 2014
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
Renal Insufficiency
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on September 30, 2014