Switching From Tenofovir Disoproxil Fumarate to Abacavir or Tenofovir Alafenamide (BACTAF)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02957864|
Recruitment Status : Recruiting
First Posted : November 8, 2016
Last Update Posted : November 8, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Renal Insufficiency,Chronic Hiv Therapeutic Agent Toxicity||Drug: tenofovir alafenamide Drug: abacavir||Phase 4|
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.
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.
96 week open label multicenter randomized non-inferiority clinical trial.
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.
Replace TDF with TAF (intervention arm) or ABC (control arm).
Main study parameters/endpoints:
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Switching to Tenofovir Alafenamide Fumarate or Abacavir in Patients With Tenofovir Disoproxil Fumarate Associated eGFR Decline. A Randomized Trial.|
|Study Start Date :||October 2016|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||February 2020|
Experimental: Switch to tenofovir alafenamide
Switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide
Drug: tenofovir alafenamide
Active Comparator: Switch to abacavir
Switch from tenofovir disoproxil fumarate (TDF) to abacavir
Other Name: ABC
- 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.
- Time to recovery of renal dysfunction [ Time Frame: 96 weeks ]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.
- Slope of eGFR-decline/increase [ Time Frame: 96 weeks ]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.
- Recovery of proteinuria [ Time Frame: 96 weeks ]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.
- Recovery of proximal tubular dysfunction [ Time Frame: 96 weeks ]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 .
- plasma HIV RNA <50c/ml [ Time Frame: 96 weeks ]HIV-RNA suppression rate <50 ABC versus TAF at week 48 and 96.
- Adverse events [ Time Frame: 96 weeks ]Tolerability of TAF versus ABC, defined in terms of adverse events (%).
- Framingham risk score [ Time Frame: 96 weeks ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02957864
|Contact: Ingeborg Wijting, MDfirstname.lastname@example.org|
|Contact: bart rijnders, MD PhDemail@example.com|
|MC Slotervaart||Not yet recruiting|
|Amsterdam, Netherlands, 1066EC|
|Contact: Saskia Vrouenraets, MD, PhD 0205129333 firstname.lastname@example.org|
|OLVG||Not yet recruiting|
|Amsterdam, Netherlands, 1091AC|
|Contact: Guido van den Berk, MD, PhD 0205999111 email@example.com|
|Rotterdam, Netherlands, 3000CA|
|Contact: ingeborg wijting, MD 0031107040704 firstname.lastname@example.org|
|Contact: bart rijnders, MD PhD 0031107033510 email@example.com|
|Maasstad ziekenhuis||Not yet recruiting|
|Rotterdam, Netherlands, 3079DZ|
|Contact: Anna Roukens, MD, PhD 0102911911 firstname.lastname@example.org|
|Study Director:||Bart Rijnders, MD PhD||Erasmus MC|