Clinical trial NCT05410496: Tenofovir Alafenamide Switching Therapy in Kidney or Liver Transplant Recipients with Chronic HBV Infection
Official title: A Prospective Cohort Study of Tenofovir Alafenamide Switching Therapy in Kidney or Liver Transplant Recipients with Chronic Hepatitis B Virus Infection
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Safety Issues
Chronic Hepatitis B
Transplant Recipient
Keywords: renal function
hepatitis
patient adherence
Lead sponsor: Taichung Veterans General Hospital
Sponsor class: OTHER
Collaborators: name: Institute of Adherence to Medication
First posted: 2022-06-08
Enrollment: 52
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: tenofovir alafenamide (TAF) has been approved to be highly effective and safe in patients with chronic hepatitis B (CHB), therefore TAF may be a good option in kidney or liver transplant patients with chronic HBV infection. The aim of this prospective cohort study is to assess the safety, efficacy, and drug adherence improvement of TAF switching therapy in kidney or liver transplant patients with HBV infection.

Detailed description: Life-long nucleos(t)ide analogue (NA) therapy has been recommended in patients with chronic HBV infection after organ transplantation, therefore the safety of long-term NA therapy is particularly important in transplant patients. Entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are recommended drugs for CHB patients in current guidelines because of their high potency in antiviral efficacy and low rate in virological resistance. However, the data of TAF therapy in transplant patients remain limited.

The potential nephrotoxicity and a decrease in bone mineral density (BMD) of TDF therapy have been reported in previous studies. TAF is a novel prodrug of tenofovir and is formulated to deliver the active metabolite to target cells more efficiently than TDF at a much lower dose, thereby reducing systemic exposure to tenofovir. In the randomized controlled trials of TDF versus TAF showed that virological and serological results were similar in both arms. However, patients in TAF arm had improved renal effects and BMD as compared to TDF. Improvement in renal function and BMD were also found in chronic hepatitis B patients who switched from TDF to TAF. Furthermore, in some retrospective studies, switching from entecavir to TAF may present a superior efficacy in HBV DNA suppression and HBsAg level reduction, and renal safety was comparable between the TAF switch group and the entecavir continuation group. Interestingly, switching from entecavir to TAF is associated with improvement of the medication adherence, which may be particularly important to patients under long-term NA therapy.

The clinical data of TAF therapy in transplant patients remain very limited, particularly in kidney transplant patients. With a high virological response rate and a low adverse effect (AE) rate in patients with CHB, TAF may be a good option for patients underwent liver or kidney transplantation.The aim of this study is to assess the safety, drug adherence, and efficacy of TAF switching therapy in kidney or liver or transplant patients with chronic HBV infection.

Eligibility criteria: Inclusion Criteria:

1. At least 20 years of age
2. Chronic HBV infection under NA therapy other than TAF
3. Underwent kidney and/ or liver transplantation
4. Without clinical or pathologic evidence of moderate or severe rejection
5. Patients who are indicated for TAF switching therapy, such as concerns in virological response, biochemical response, drug compliance, or safety issues to other NAs.

Exclusion Criteria:

1. End stage renal disease (eGFR \< 15 mL/min/1.73m2)
2. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
3. Any active malignancies
4. Pregnant or breast-feeding women
5. Known allergy to tenofovir-contained regimens

Primary outcomes:
measure: Estimated glomerular filtration rate
timeFrame: week 48
measure: HBV viral load
timeFrame: week 48
measure: Drug adherence score
timeFrame: week 48 (higher scores mean a better outcome)
Secondary outcomes:
measure: Estimated glomerular filtration rate
timeFrame: week 144
measure: HBV viral load
timeFrame: week 144
measure: Drug adherence score
timeFrame: week 144 (higher scores mean a better outcome)
measure: Bone mineral density
timeFrame: week 144
measure: Alanine aminotransferase
timeFrame: week 144
measure: Quantitative HBsAg
timeFrame: week 144
measure: Liver fibrosis elastography
timeFrame: week 144
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
Study officials:
affiliation: Taichung Veterans General Hospital
name: Teng-Yu Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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