Trial document

This trial has been registered retrospectively.
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Trial Description

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Long term efficacy and safety of tenofovir alafenamide fumarate (TAF) in patients with chronic hepatitis B virus(HBV) infections: an observational, non-interventional trial (TOUGH trial)

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Trial Acronym


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URL of the Trial


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Brief Summary in Lay Language

Observation of safety and efficacy of tenofovir alafenamide fumarat (TAF) in patients with Hepatitis B mono-infection

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Brief Summary in Scientific Language

The nucleotide analogue (NA) tenofovir disoproxil fumarate (TDF) has become a mainstay in the treatment of chronic hepatitis B virus (HBV) infections worldwide. TDF is characterized by both high antiviral potency and high genetic barrier against resistance development with high antiviral activity against wild type or HBV variants associated with resistance.To date no confirmed genotypic HBV resistance mutation against TDF in CHB has been reported. Although generally well tolerated, treatment with TDF has rarely been associated with a decline of glomerular filtration rate. In addition, decrease of mineral bone density has been reported. Discontinuation of the drug may improve kidney function but sequelae may remain. Tenofovir alafenamide fumarate (TAF) is also a prodrug of tenofovir which has been licensed for chronic hepatitis B in Germany since 09.01.2017. The use of TAF allows lower dosages as TDF achieving the same level of antiviral potency. In phase 3 clinical trials of TAF, no inferiority to TDF could be established with lower incidence of side effects, especially nephrotoxicity and mineral bone density. In vitro studies have shown that TAF also exerts antiviral potency against HBV variants associated with resistance development. Current experince of treatment with TAF in chronic hepatitis B infection derives from randomized clinical trials. Focus of these trials were were efficacy and safety measured by virological and biochemical markers, which monitor potential side effects associated with tenofovir such as nephrotoxicity, decline of mineral bone density and elevation of lipid panel.
The current European guideline (EASL 2017. Clinical Practice Guidelines on the management of hepatitis B virus infection) recommends the monitoring of liver function and inflammation, renal function and mineral bone density before initiating treatment and during administration of TAF.
The currrent drug information of TAF recommends regular surveillance of hepatotoxicity und nephrotoxicity, monitoring of ALT-levels (Fachinformation Vemlidy 2017).
Since most patients do not qualify for clinical trials, safety and efficacy of TAF needs to be evaluated in a real-world setting.
The aim of our prospective non interventional trial ist to evalaute the efficacy and safety in patients who receive treatment with TAF to the discretion of their physician.

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Organizational Data

  •   DRKS00017414
  •   2019/09/25
  •   [---]*
  •   yes
  •   Approved
  •   294/17-ek, Ethikkommission an der Medizinischen Fakultät der Universität Leipzig
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Secondary IDs

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Health Condition or Problem studied

  •   B18.1 -  Chronic viral hepatitis B without delta-agent
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Interventions/Observational Groups

  •   Patients receiving treatment with tenofovir alafenamide fumarat (TAF) are monitored for antiviral efficacy and safety for the duration of 3 years. In accordance with international guidelines and the current drug information regular surveillance of laboratory markers and side effects is carried out.
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  •   Non-interventional
  •   Observational study
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   N/A
  •   No
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Primary Outcome

- Percentage of patients achieving undetectable levels of HBV DNA after 6, 12, 24 and 36 months of treatment with TAF
- Percentage of patients achieving HBsAg loss during treatment with TAF
- Percentage of patients achieving HBeAg seroconversion treatment with TAF
- Percentage of patients developing a decrease in renal function during treatment

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Secondary Outcome

- side effects during treatment with TAF
- Changes in HBsAg levels during TAF treatment
- Percentage of patients with virologic failure defined as:
- Confirmed re-increase in HBV DNA levels > 1 log after initial response to TAF
- Absence of decrease of HBV DNA > 1 log wihin 12 month of TAF treatment -
Partial response: HBV DNA levels > 400 copies/mL after 1, 2 and 3 years of TAF treatment
- changes of ALT levels during tough treatment
- changes of renal function during treatment
- Changes in mineral bone density and lipid panel if diagnostic test are carried out to the disretion of the current physician
- changes of liver stiffness during treatment if available
- Changes in the HBV polymerase gene in patients with virologic failure to TAF treatment - Change in liver stiffness during TAF treatment

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
  • Doctor's Practice 
  • Doctor's Practice 
  • Doctor's Practice 
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  •   Actual
  •   2018/10/01
  •   200
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. Chronic HBV infection diagnosed at least 6 months prior to inclusion in trial (HBsAg positive > 6 months)
2. Patients receiving newly initiated treatment with TAF or
3. Treatment experienced patients who switch from ongoing antiviral treatment to TAF
3. Age ≥ 18 years
4. Signed informed consent form

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Exclusion Criteria

1. Patients who are not willing or able to sign informed consent.
2. Patients with HBV/HIV or HBV/HCV or HBV/HDV coinfection

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    • Universitätsklinikum Leipzig
    • Liebigstr. 18
    • 04103  Leipzig
    • Germany
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    • Klinik für Gastroenterologie, Universitätsklinikum Leipzig
    • Mr.  PD Dr. med.  Florian  van Bömmel 
    • Liebigstr. 20
    • 04103  Leipzig
    • Germany
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    • Klinik für Gastroenterologie, Universitätsklinikum Leipzig
    • Ms.  Claudia  Breithaupt 
    • Liebigstr. 20
    • 04103  Leipzig
    • Germany
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Sources of Monetary or Material Support

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    • Gilead Sciences
    • 333 Lakeside Drive
    • 94404  Foster City
    • United States
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  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.