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.

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Key information

Conditions

Hepatitis B Blood-Borne Infections Communicable Diseases DNA Virus Infections Digestive System Diseases Hepadnaviridae Infections Hepatitis Hepatitis, Viral, Human Infections Liver Diseases Renal Failure With Tubular Necrosis Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

CHU d'Amiens, Amiens, France

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

plasma and urine samples, sample with ADN

Biological

plasma and urine samples every three months Sample with ADN at baseline

Primary outcomes

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.

Secondary outcomes

the prevalence at baseline of "subclinical" proximal tubular abnormalities

Time frame: 1 day

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.

Sponsors and collaborators

Lead sponsor

University Hospital, Limoges

Other

Registry information

Official study 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.

Acronym: HBVSECURE

Important dates

Study start: 2011
Primary completion: 2013
Study completion: 2015
First posted: Dec 28, 2011
Registry last updated: Feb 24, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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