Renal InsufficiencyPhase 4NCT04391608
TDF Dose Adjustment VS. Switching to TAF in TDF-experienced CHB Patients With Renal Impairment
A Phase 4 study testing Switching to Tenofovir Alafenamide in people with Renal Insufficiency and Tenofovir, run by Mahidol University at 1 site in Thailand.
Trial summary
Tenofovir is a nucleotide analog drug that works against both Human immunodeficiency virus (HIV) and HBV. TDF and TAF are prodrug of Tenofovir. TAF has a higher plasma stability than TDF, which makes TDF require a higher dose to get the concentration of drugs in the liver equal to the amount of TAF. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Insufficiency, Tenofovir
- What is being tested?
- Switching to Tenofovir Alafenamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteThailand
- Study dates
- 9 Nov 2019to 31 Jul 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 18 - 75 years old
- Chronic hepatitis B virus infection
- Reduced renal function and need to adjust the dose of TDF
- Have an eGFR of > 15 ml / min.
- HBV DNA viral load levels < 10 U/mL in the last 3 months before participating in the project
- No HCC by Ultrasonography of the upper abdomen or CT 3-phase of liver or MRI liver in the 3 months before participating in the project.
Who cannot join
- HIV infection or hepatitis C or hepatitis D co-infection
- Decompensated cirrhosis, including variceal bleeding, ascites, hepatic encephalopathy
- Active hepatocellular carcinoma or during the 3 years after treatment
- Solid organ transplantation or Bone marrow transplantation
- Chronic kidney disease caused by glomerulonephritis, tubulo-interstitial nephritis), Obstructive uropathy or autosomal dominant polycystic kidney, and Kidney disease from other causes
- Diabetes with HbA1c> 8 or uncontrollable hypertension
Show all 10Show fewer
- Active malignancy of cancer in other organs in the last 3 years
- History of receiving non-steroidal anti-inflammatory drugs (NSAIDs) or other nephrotoxic drugs within the past 1 month (except tenofovir) (For patients receiving NSAIDS after participating in this study, patients were advised to stop taking NSAIDs but not exclude from the study)
- Receive immunosuppressive drug
- Pregnancy
Trial locations and contacts
1 site in 1 country.
Thailand1 site, 1 recruiting
- Recruiting
Faculty of Medicine Siriraj Hospital, Mahidol University
Bangkok Noi, Bangkok, 10700
Faculty of Medicine Siriraj Hospital, Mahidol University, 6624192636
About this study
Official title: Randomized Trial of Tenofovir Disoproxil Fumerate Dose Adjustment VS. Switching to Tenofovir Alafenamide in Tenofovir Disoproxil Fumarate-experienced Chronic Hepatitis B Patients With Renal Impairment
Tenofovir is a nucleotide analog drug that works against both Human immunodeficiency virus (HIV) and HBV. TDF and TAF are prodrug of Tenofovir. TAF has a higher plasma stability than TDF, which makes TDF require a higher dose to get the concentration of drugs in the liver equal to the amount of TAF.
Previous studies have shown the effects of TAF once daily and TDF once daily on kidney function and bone mass. The efficacy of TAF in virus suppression is comparable to TDF, but the effect on the kidneys and bone mass from TAF has less side effects than TDF. In addition, changing the medication from TDF to TAF shows that kidney function tends to improve.
Hepatitis B patients taking TDF have adjusted their dosage due to impair renal function, for example, from 1 time per day to every 48 hours or every 72 hours. This group of patients does not have a clear evidence-based recommendation for choosing a reduced dose of TDF or change to TAF. Therefore, the main objective of this study is to study patients with hepatitis B who have taken TDF and have renal function impairment that have been adjusted. Taking the same medicine with dose adjustment or changing the drug to TAF which treatment will more improve the kidney function.
Read the detailed description
Hepatitis B virus is a global public health problem. More than 250 million people are infected worldwide. These infections lead to chronic hepatitis, cirrhosis and liver cancer. According to past statistics, infection with hepatitis B virus is an important factor of death in 880,000 patients per year.
Patients who receiving natural immunity or receiving antiretroviral therapy that loss of hepatitis B surface antigen (HBsAg loss) reduce the risk of cirrhosis and hepatocellular carcinoma (HCC). HBsAg loss is now considered the target of treatment.
Nucleot(s)ide is an antiviral drug that can reduce the number of viruses, reduce the risk of HCC and death from Hepatitis B viral infection. The most widely used drugs are Lamivudine (LMV), Entecavir (ETV), Tenofovir disoproxil fumerate (TDF) and Tenofovir alafenamide (TAF). However, Nucleotide is unable to eliminate the Hepatitis B virus from the liver cells of the infected person due to covalently closed. circular DNA (cccDNA), which is a template for viral replication. Therefore, long-term Nucleotide therapy is necessary. As a result, patients may have side effects from the treatment when taking medication for a long time, such as viral resistance in Lamivudine, deterioration of kidney function and osteoporosis in Tenofovir.
Tenofovir is a nucleotide analog drug that works against both Human immunodeficiency virus (HIV) and HBV. TDF and TAF are prodrug of Tenofovir. TAF has a higher plasma stability than TDF, which makes TDF require a higher dose to get the concentration of drugs in the liver equal to the amount of TAF.
The side effects of Tenofovir treatment found on the kidneys and bones which are problems for long-term treatment. It is recommended to reduce the dose of TDF in patients with renal function reduced to less than 50 ml / min as shown in Table but do not have to adjust the dose of TAF except when the GFR value is less than 15 ml / min. it is recommended to stop taking TAF if severe renal impairment.
Previous studies have shown the effects of TAF once daily and TDF once daily on kidney function and bone mass. The efficacy of TAF in virus suppression is comparable to TDF, but the effect on the kidneys and bone mass from TAF has less side effects than TDF. In addition, changing the medication from TDF to TAF shows that kidney function tends to improve. Therefore, there is a recommendation in the practice guideline to change from TDF to TAF or ETV in patients who use TDF and there is a risk of kidney problems or thin bone mass based on history for LMV resistance (if LMV resistance, ETV should not be used because HBV is more resistant to ETV).
Hepatitis B patients taking TDF have adjusted their dosage due to impair renal function, for example, from 1 time per day to every 48 hours or every 72 hours. This group of patients does not have a clear evidence-based recommendation for choosing a reduced dose of TDF or change to TAF. Therefore, the main objective of this study is to study patients with hepatitis B who have taken TDF and have renal function impairment that have been adjusted. Taking the same medicine with dose adjustment or changing the drug to TAF which treatment will more improve the kidney function.
- Conditions
- Renal Insufficiency, Tenofovir
- Being tested
- Switching to Tenofovir Alafenamide
- Keywords
- Tenofovir, Tenofovir disoproxil fumarate, Tenofovir alafenamide, TDF, TAF, Renal, Impairment, Insufficiency
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Switching to Tenofovir AlafenamideDrug
Also called Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide
Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir Alafenamide | Active comparator | Tenofovir Alafenamide 25 mg/day Receives: Drug: Switching to Tenofovir Alafenamide |
| TDF dose reduction | No intervention | TDF dose reduction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal safety assessed by changes in eGFR
To study renal function changes by measuring eGFR during Tenofovir disoproxil fumarate (TDF) dose reduction versus switching to Tenofovir alafenamide (TAF) after 48 weeks of treatment in chronic hepatitis B with impaired kidney function
Measured: 48 weeks
Secondary outcomes (6)
Renal safety assessed by changes in urine sugar (0 to 4+)
To study kidney function changes by measuring urine sugar (0 to 4+) during TDF dose reduction compared to switching to TAF after 48 weeks of treatment
Measured: 48 weeks
Renal safety assessed by changes in urine protein creatinine ratio
To study kidney function changes by measuring urine protein creatinine ratio during TDF dose reduction compared to switching to TAF after 48 weeks of treatment
Measured: 48 weeks
Renal safety assessed by changes in urine ß2-microglobulin (µg/mL)
To study kidney function changes by measuring urine ß2-microglobulin (µg/mL) during TDF dose reduction compared to switching to TAF after 48 weeks of treatment
Measured: 48 weeks
Renal safety assessed by changes in urine phosphate (mg/dL)
To study kidney function changes by measuring urine phosphate(mg/dL) during TDF dose reduction compared to switching to TAF after 48 weeks of treatment
Measured: 48 weeks
Renal safety assessed by changes in urine neutrophil gelatinase-associated lipocalin (NGAL) (ng/mL)
To study kidney function changes by measuring urine neutrophil gelatinase-associated lipocalin (NGAL) (ng/mL) during TDF dose reduction compared to switching to TAF after 48 weeks of treatment
Measured: 48 weeks
Efficacy of viral suppression assessed by amount of hepatitis B (HBV DNA) (IU/mL)
To study the efficacy of treatment by measuring amount of hepatitis B (HBV DNA) (IU/mL) during the dose reduction of TDF compared to switching to TAF after 48 weeks of treatment
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2020
- Study start9 Nov 2019
- Primary completion31 Jul 2022 (estimated)
- Study completion31 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal InsufficiencyStudies of the same condition, open and under way.
- More trials run by Mahidol UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mahidol University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Watcharasak Chotiyaputta, Mahidol University
- Investigators
- Watcharasak Chotiyaputta, Asso Prof, Principal investigator, Mahidol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04391608
- Sponsor's protocol ID
- Si 798/2019
- Status last verified
- Mar 2022
- First submitted
- 6 May 2020
- Last updated
- 8 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Tenofovir Disoproxil Fumerate Dose Adjustment VS. Switching to Tenofovir Alafenamide in Tenofovir Disoproxil Fumarate-experienced Chronic Hepatitis B Patients With Renal Impairment
- ClinicalTrials.gov ID
- NCT04391608
- Acronym / sponsor ID
- Si 798/2019
- Conditions
- Renal Insufficiency, Tenofovir
- Keywords
- Tenofovir, Tenofovir disoproxil fumarate, Tenofovir alafenamide, TDF, TAF, Renal, Impairment, Insufficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Mahidol UniversityUniversity, hospital or other
- Study start
- 9 Nov 2019 (actual)
- Primary completion
- 31 Jul 2022 (estimated)
- Study completion
- 31 Jul 2022 (estimated)
- First posted
- 18 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tenofovir is a nucleotide analog drug that works against both Human immunodeficiency virus (HIV) and HBV. TDF and TAF are prodrug of Tenofovir. TAF has a higher plasma stability than TDF, which makes TDF require a higher dose to get the concentration of drugs in the liver equal to the amount of TAF.
Previous studies have shown the effects of TAF once daily and TDF once daily on kidney function and bone mass. The efficacy of TAF in virus suppression is comparable to TDF, but the effect on the kidneys and bone mass from TAF has less side effects than TDF. In addition, changing the medication from TDF to TAF shows that kidney function tends to improve.
Hepatitis B patients taking TDF have adjusted their dosage due to impair renal function, for example, from 1 time per day to every 48 hours or every 72 hours. This group of patients does not have a clear evidence-based recommendation for choosing a reduced dose of TDF or change to TAF. Therefore, the main objective of this study is to study patients with hepatitis B who have taken TDF and have renal function impairment that have been adjusted. Taking the same medicine with dose adjustment or changing the drug to TAF which treatment will more improve the kidney function.
Detailed description
Hepatitis B virus is a global public health problem. More than 250 million people are infected worldwide. These infections lead to chronic hepatitis, cirrhosis and liver cancer. According to past statistics, infection with hepatitis B virus is an important factor of death in 880,000 patients per year.
Patients who receiving natural immunity or receiving antiretroviral therapy that loss of hepatitis B surface antigen (HBsAg loss) reduce the risk of cirrhosis and hepatocellular carcinoma (HCC). HBsAg loss is now considered the target of treatment.
Nucleot(s)ide is an antiviral drug that can reduce the number of viruses, reduce the risk of HCC and death from Hepatitis B viral infection. The most widely used drugs are Lamivudine (LMV), Entecavir (ETV), Tenofovir disoproxil fumerate (TDF) and Tenofovir alafenamide (TAF). However, Nucleotide is unable to eliminate the Hepatitis B virus from the liver cells of the infected person due to covalently closed. circular DNA (cccDNA), which is a template for viral replication. Therefore, long-term Nucleotide therapy is necessary. As a result, patients may have side effects from the treatment when taking medication for a long time, such as viral resistance in Lamivudine, deterioration of kidney function and osteoporosis in Tenofovir.
Tenofovir is a nucleotide analog drug that works against both Human immunodeficiency virus (HIV) and HBV. TDF and TAF are prodrug of Tenofovir. TAF has a higher plasma stability than TDF, which makes TDF require a higher dose to get the concentration of drugs in the liver equal to the amount of TAF.
The side effects of Tenofovir treatment found on the kidneys and bones which are problems for long-term treatment. It is recommended to reduce the dose of TDF in patients with renal function reduced to less than 50 ml / min as shown in Table but do not have to adjust the dose of TAF except when the GFR value is less than 15 ml / min. it is recommended to stop taking TAF if severe renal impairment.
Previous studies have shown the effects of TAF once daily and TDF once daily on kidney function and bone mass. The efficacy of TAF in virus suppression is comparable to TDF, but the effect on the kidneys and bone mass from TAF has less side effects than TDF. In addition, changing the medication from TDF to TAF shows that kidney function tends to improve. Therefore, there is a recommendation in the practice guideline to change from TDF to TAF or ETV in patients who use TDF and there is a risk of kidney problems or thin bone mass based on history for LMV resistance (if LMV resistance, ETV should not be used because HBV is more resistant to ETV).
Hepatitis B patients taking TDF have adjusted their dosage due to impair renal function, for example, from 1 time per day to every 48 hours or every 72 hours. This group of patients does not have a clear evidence-based recommendation for choosing a reduced dose of TDF or change to TAF. Therefore, the main objective of this study is to study patients with hepatitis B who have taken TDF and have renal function impairment that have been adjusted. Taking the same medicine with dose adjustment or changing the drug to TAF which treatment will more improve the kidney function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir Alafenamide | Active comparator | Drug: Switching to Tenofovir AlafenamideTenofovir Alafenamide 25 mg/day |
| TDF dose reduction | No intervention | –TDF dose reduction |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age between 18 - 75 years old
- Chronic hepatitis B virus infection
- Reduced renal function and need to adjust the dose of TDF
- Have an eGFR of > 15 ml / min.
- HBV DNA viral load levels < 10 U/mL in the last 3 months before participating in the project
Key exclusion criteria (10 listed)
- HIV infection or hepatitis C or hepatitis D co-infection
- Decompensated cirrhosis, including variceal bleeding, ascites, hepatic encephalopathy
- Active hepatocellular carcinoma or during the 3 years after treatment
- Solid organ transplantation or Bone marrow transplantation
- Chronic kidney disease caused by glomerulonephritis, tubulo-interstitial nephritis), Obstructive uropathy or autosomal dominant polycystic kidney, and Kidney disease from other causes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Switching to Tenofovir AlafenamideAlso: Switching from Tenofovir Disoproxil Fumarate to Tenofovir AlafenamideSwitching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide | Drug | Tenofovir Alafenamide |
Primary outcome
Renal safety assessed by changes in eGFR
Time frame: 48 weeks
To study renal function changes by measuring eGFR during Tenofovir disoproxil fumarate (TDF) dose reduction versus switching to Tenofovir alafenamide (TAF) after 48 weeks of treatment in chronic hepatitis B with impaired kidney function
6 secondary outcomes
Renal safety assessed by changes in urine sugar (0 to 4+)
Time frame: 48 weeks
Renal safety assessed by changes in urine protein creatinine ratio
Time frame: 48 weeks
Renal safety assessed by changes in urine ß2-microglobulin (µg/mL)
Time frame: 48 weeks
Renal safety assessed by changes in urine phosphate (mg/dL)
Time frame: 48 weeks
Renal safety assessed by changes in urine neutrophil gelatinase-associated lipocalin (NGAL) (ng/mL)
Time frame: 48 weeks
Efficacy of viral suppression assessed by amount of hepatitis B (HBV DNA) (IU/mL)
Time frame: 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Watcharasak Chotiyaputta, Asso Prof principal investigator
Mahidol University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Switching to Tenofovir Alafenamide in people with Renal Insufficiency and Tenofovir, run by Mahidol University at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Watcharasak Chotiyaputta, Asso Prof (ุุุ6624197281, watcharasak.cho@mahidol.ac.th), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Renal safety assessed by changes in eGFR (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2022.