Renal Insufficiency,ChronicPhase 4BACTAFNCT02957864
Switching From Tenofovir Disoproxil Fumarate to Abacavir or Tenofovir Alafenamide
A Phase 4 study testing tenofovir alafenamide and abacavir in people with Renal Insufficiency,Chronic and Hiv, run by Erasmus Medical Center at 5 sites in Netherlands.
Trial summary
Tenofovir disoproxil fumarate (TDF) is one of the most frequently used drugs to treat HIV. Long term use of TDF can induce renal toxicity. Tenofovir alafenamide (TAF) is a new pro-drug of Tenofovir which has not been associated with renal toxicity and may therefore be a good substitute for TDF in patients with TDF… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Insufficiency,Chronic, Hiv, Therapeutic Agent Toxicity
- What is being tested?
- tenofovir alafenamide and abacavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 5 sitesNetherlands
- Study dates
- Oct 2016to Sep 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-positive documented by ELISA or Western Blot or plasma HIV-RNA > 1000 copies/mL.
- 18 years or older. Stable on TDF/FTC or TDF/3TC for ≥12 months (365 days) in combination with a third antiretroviral agent (NNRTI, INI, or PI) and with an unchanged third agent for at least 1 month.
- HIV-1 RNA <50 copies/mL for ≥ 6 months. Patient is negative for the HLA B5701 allele.
- Confirmed/probable TDF-related accelerated eGFR decline (one of the following):
- Accelerated eGFR decline: mean of > 3 mL/min/year since start TDF after ≥5 years of TDF exposure.
- Confirmed eGFR < 70 mL/min in patients with baseline eGFR > 90 mL/min at start of TDF.
Show all 13Show fewer
- eGFR decrease > 25% compared to baseline eGFR at TDF-initiation.
- Absence of other causes of eGFR decline:
- Diabetic patients with diabetic nephropathy (defined as an eGFR decline and uACR>30mg/mmol with uAPR >/=0.4, or biopsy proven).
- Hypertensive patients (defined as the use of antihypertensives or untreated systolic (>=160mmHg) or diastolic (>=95mmHg) hypertension) in combination with hypertensive nephropathy (defined as eGFR decline with uACR>30mg/mmol with uAPR>/=0.4, or biopsy proven).
- Nephrotic syndromes/nephrotic range proteinuria (uACR >300mg/mmol and uAPR ≥ 0.4, or total 24hrs proteinuria >3.5g/24hr, or biopsy proven) Nephrotic syndromes including rapid progressive glomerulonephritis and tubular interstitial nephritis (defined as active urine sediment with erythrocyturia and leucocyturia and proteinuria with eGFR decline, with or without the presence of systemic disease, or biopsy proven).
- Obvious other renal toxic effects related to lifestyle or medication (e.g. creatin use) suspected by the investigators or biopsy proven.
- Concomittantly used medication does not interfere with trial procedures (on investigators' discretion).
Who cannot join
- Likely other cause (as defined above) of the accelerated GFR decline. HLA-B5701 positivity. Active hepatitis C or B. Documented intermediate or high level resistance to ABC. eGFR <30ml/min. Any other disease or medical condition that, in the opinion of the investigators, would interfere with the safety of the participant or the conduct of the trial.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Netherlands5 sites, 5 recruiting
- Recruiting
MC Slotervaart
Amsterdam, 1066EC
Saskia Vrouenraets, MD, PhD, 0205129333, saskia.vrouenraets@slz.nl
- Not yet recruiting
OLVG
Amsterdam, 1091AC
Guido van den Berk, MD, PhD, 0205999111, g.e.l.vandenberk@olvg.nl
- Recruiting
Ziekenhuis Rijnstate
Arnhem, Gelderland
Marc Claassen, PhD
- Recruiting
Erasmus MC
Rotterdam, 3000CA
ingeborg wijting, MD, 0031107040704, i.wijting@erasmusmc.nl
bart rijnders, MD PhD, 0031107033510, b.rijnders@erasmusmc.nl
- Recruiting
Maasstad ziekenhuis
Rotterdam, 3079DZ
Anna Roukens, MD, PhD, 0102911911, roukensa@maasstadziekenhuis.nl
About this study
Official title: Switching to Tenofovir Alafenamide Fumarate or Abacavir in Patients With Tenofovir Disoproxil Fumarate Associated eGFR Decline. A Randomized Trial.
Tenofovir disoproxil fumarate (TDF) is one of the most frequently used drugs to treat HIV. Long term use of TDF can induce renal toxicity. Tenofovir alafenamide (TAF) is a new pro-drug of Tenofovir which has not been associated with renal toxicity and may therefore be a good substitute for TDF in patients with TDF induced renal toxicity. Abacavir (ABC) is another drug that can be used for the treatment of HIV and is not associated with renal toxicity.
In this study the investigators will compare the effect on renal function of a switch from TDF to TAF with a switch from TDF to ABC in patients with TDF induced renal insufficiency.
Read the detailed description
The majority of HIV-1 infected patients in resource rich countries receive the tenofovir prodrug tenofovir disoproxil fumarate (TDF) as part of their combination antiretroviral therapy (cART). Long-term exposure to TDF can be associated with an accelerated estimated glomerular filtration rate (eGFR) decline and proximal renal tubular dysfunction (PTD, see definition below). The current practice in patients in which TDF related renal toxicity becomes apparent is to substitute abacavir (ABC) for TDF. However, ABC is contraindicated in patients with HLAB57*01 and has been associated with an increased risk of cardiovascular disease in large HIV cohort studies, but not in randomized clinical trials. Recently, a new tenofovir prodrug, tenofovir alafenamide (TAF) was developed by Gilead Sciences and is available in a coformulation with emtricitabine (FTC). Due to the targeted delivery of tenofovir inside the CD4 positive cell by this prodrug, only 25 mg TAF is needed for the same antiviral effect observed in patients taking 250 mg of TDF and this lower TAF dose leads to 90% lower serum levels of tenofovir. In recently completed phase III studies in which patients with a normal kidney function where included, this lower tenofovir exposure in patients on TAF was shown to prevent off-target renal and bone toxicity in comparison with patients taking TDF. However, whether an already established TDF related renal toxicity in a HIV patient can be reversed after a switch to TAF, remains to be shown.
Objective:
To study the renal safety when HIV patients with TDF related renal toxicity switch to TAF compared to the current practice of switching to ABC.
Study design:
96 week open label multicenter randomized non-inferiority clinical trial.
Study population:
HIV-1 infected adults, suppressed HIV-RNA <50c/mL on a TDF containing antiretroviral regimen, with signs of TDF related renal toxicity as indicated by an accelerated eGFR decline.
Intervention:
Replace TDF with TAF (intervention arm) or ABC (control arm).
Main study parameters/endpoints:
Primary endpoint:
Recovery of renal dysfunction in the TAF arm versus the ABC arm at 48 weeks after the switch from TDF to TAF or ABC using the time to the first eGFR within 75% of the eGFR at the time of TDF initiation.
Secondary endpoints:
See below
- Conditions
- Renal Insufficiency,Chronic, Hiv, Therapeutic Agent Toxicity
- Being tested
- tenofovir alafenamide, abacavir
- Medical subject headings
- Renal Insufficiency, Chronic, Acquired Immunodeficiency Syndrome, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tenofovir alafenamideDrug
Also called Descovy, TAF
abacavirDrug
Also called ABC
| Study group | Role | What they receive |
|---|---|---|
| Switch to tenofovir alafenamide | Experimental | Switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide Receives: Drug: tenofovir alafenamide |
| Switch to abacavir | Active comparator | Switch from tenofovir disoproxil fumarate (TDF) to abacavir Receives: Drug: abacavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recovery of renal insufficiency
Recovery of renal dysfunction in the TAF arm versus the ABC arm at 48 weeks after the switch from TDF to TAF or ABC using the time to the first eGFR within 75% of the eGFR at the time of TDF initiation.
Measured: 48 weeks
Secondary outcomes (7)
Time to recovery of renal dysfunction
The between group differences (TAF vs ABC) with respect to the time to recovery of renal dysfunction (eGFR improvement to within 75% of eGFR at TDF initiation) at week 96, with adjustment for potentially important confounders.
Measured: 96 weeks
Slope of eGFR-decline/increase
The mean eGFR at week 48 and 96 on ABC and TAF will be compared to week 0. The slopes of eGFR-decline/increase between week 0, week 48 and 96 will be compared between the ABC and TAF group.
Measured: 96 weeks
Recovery of proteinuria
The median (IQR) of uPCR, uACR, uAPR, uB2MG/CR changes at week 48 and 96 compared to week 0 within the ABC and TAF group and difference in change between both groups.
Measured: 96 weeks
Recovery of proximal tubular dysfunction
Changes in the number of patients with at least 2 markers of PTD from week 0 to week 48 within the ABC and TAF group and difference in change of PTD markers between both groups .
Measured: 96 weeks
plasma HIV RNA <50c/ml
HIV-RNA suppression rate <50 ABC versus TAF at week 48 and 96.
Measured: 96 weeks
Adverse events
Tolerability of TAF versus ABC, defined in terms of adverse events (%).
Measured: 96 weeks
Framingham risk score
Change in framingham risk-score, blood pressure, lipids and inflammation parameters at week 0, 48 and 96 within the ABC and TAF group and comparison of between group differences of these parameters.
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2016 (estimated)
- Study startOct 2016
- Primary completionJun 2020 (estimated)
- Study completionSep 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Insufficiency,ChronicStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe 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
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Principal investigator, Bart Rijnders, Erasmus Medical Center
- Investigators
- Bart Rijnders, MD PhD, Study director, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02957864
- Sponsor's protocol ID
- NL55668.078.16
- Acronym
- BACTAF
- Status last verified
- Jan 2020
- First submitted
- 4 Nov 2016
- Last updated
- 28 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Switching to Tenofovir Alafenamide Fumarate or Abacavir in Patients With Tenofovir Disoproxil Fumarate Associated eGFR Decline. A Randomized Trial.
- ClinicalTrials.gov ID
- NCT02957864
- Acronym / sponsor ID
- BACTAF / NL55668.078.16
- Conditions
- Renal Insufficiency,Chronic, Hiv, Therapeutic Agent Toxicity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Oct 2016
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Sep 2020 (estimated)
- First posted
- 8 Nov 2016 (estimated)
- 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 disoproxil fumarate (TDF) is one of the most frequently used drugs to treat HIV. Long term use of TDF can induce renal toxicity. Tenofovir alafenamide (TAF) is a new pro-drug of Tenofovir which has not been associated with renal toxicity and may therefore be a good substitute for TDF in patients with TDF induced renal toxicity. Abacavir (ABC) is another drug that can be used for the treatment of HIV and is not associated with renal toxicity.
In this study the investigators will compare the effect on renal function of a switch from TDF to TAF with a switch from TDF to ABC in patients with TDF induced renal insufficiency.
Detailed description
The majority of HIV-1 infected patients in resource rich countries receive the tenofovir prodrug tenofovir disoproxil fumarate (TDF) as part of their combination antiretroviral therapy (cART). Long-term exposure to TDF can be associated with an accelerated estimated glomerular filtration rate (eGFR) decline and proximal renal tubular dysfunction (PTD, see definition below). The current practice in patients in which TDF related renal toxicity becomes apparent is to substitute abacavir (ABC) for TDF. However, ABC is contraindicated in patients with HLAB57*01 and has been associated with an increased risk of cardiovascular disease in large HIV cohort studies, but not in randomized clinical trials. Recently, a new tenofovir prodrug, tenofovir alafenamide (TAF) was developed by Gilead Sciences and is available in a coformulation with emtricitabine (FTC). Due to the targeted delivery of tenofovir inside the CD4 positive cell by this prodrug, only 25 mg TAF is needed for the same antiviral effect observed in patients taking 250 mg of TDF and this lower TAF dose leads to 90% lower serum levels of tenofovir. In recently completed phase III studies in which patients with a normal kidney function where included, this lower tenofovir exposure in patients on TAF was shown to prevent off-target renal and bone toxicity in comparison with patients taking TDF. However, whether an already established TDF related renal toxicity in a HIV patient can be reversed after a switch to TAF, remains to be shown.
Objective:
To study the renal safety when HIV patients with TDF related renal toxicity switch to TAF compared to the current practice of switching to ABC.
Study design:
96 week open label multicenter randomized non-inferiority clinical trial.
Study population:
HIV-1 infected adults, suppressed HIV-RNA <50c/mL on a TDF containing antiretroviral regimen, with signs of TDF related renal toxicity as indicated by an accelerated eGFR decline.
Intervention:
Replace TDF with TAF (intervention arm) or ABC (control arm).
Main study parameters/endpoints:
Primary endpoint:
Recovery of renal dysfunction in the TAF arm versus the ABC arm at 48 weeks after the switch from TDF to TAF or ABC using the time to the first eGFR within 75% of the eGFR at the time of TDF initiation.
Secondary endpoints:
See below
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Switch to tenofovir alafenamide | Experimental | Drug: tenofovir alafenamideSwitch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide |
| Switch to abacavir | Active comparator | Drug: abacavirSwitch from tenofovir disoproxil fumarate (TDF) to abacavir |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- HIV-positive documented by ELISA or Western Blot or plasma HIV-RNA > 1000 copies/mL.
- 18 years or older. Stable on TDF/FTC or TDF/3TC for ≥12 months (365 days) in combination with a third antiretroviral agent (NNRTI, INI, or PI) and with an unchanged third agent for at least 1 month.
- HIV-1 RNA <50 copies/mL for ≥ 6 months. Patient is negative for the HLA B5701 allele.
- Accelerated eGFR decline: mean of > 3 mL/min/year since start TDF after ≥5 years of TDF exposure.
- Confirmed eGFR < 70 mL/min in patients with baseline eGFR > 90 mL/min at start of TDF.
Key exclusion criteria (1 listed)
- Likely other cause (as defined above) of the accelerated GFR decline. HLA-B5701 positivity. Active hepatitis C or B. Documented intermediate or high level resistance to ABC. eGFR <30ml/min. Any other disease or medical condition that, in the opinion of the investigators, would interfere with the safety of the participant or the conduct of the trial.
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 |
|---|---|---|
| tenofovir alafenamideAlso: Descovy, TAF | Drug | Switch to tenofovir alafenamide |
| abacavirAlso: ABC | Drug | Switch to abacavir |
Primary outcome
Recovery of renal insufficiency
Time frame: 48 weeks
Recovery of renal dysfunction in the TAF arm versus the ABC arm at 48 weeks after the switch from TDF to TAF or ABC using the time to the first eGFR within 75% of the eGFR at the time of TDF initiation.
7 secondary outcomes
Time to recovery of renal dysfunction
Time frame: 96 weeks
Slope of eGFR-decline/increase
Time frame: 96 weeks
Recovery of proteinuria
Time frame: 96 weeks
Recovery of proximal tubular dysfunction
Time frame: 96 weeks
plasma HIV RNA <50c/ml
Time frame: 96 weeks
Adverse events
Time frame: 96 weeks
Framingham risk score
Time frame: 96 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2020.
- 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.
Bart Rijnders, MD PhD study director
Erasmus Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing tenofovir alafenamide and abacavir in people with Renal Insufficiency,Chronic and Hiv, run by Erasmus Medical Center at 5 sites in Netherlands.
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 13 inclusion and 1 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 28 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. 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 Ingeborg Wijting, MD (0031107040704, i.wijting@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recovery of renal insufficiency (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 28 Jan 2020.