We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Bart Rijnders, Erasmus Medical Center

Brief 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 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

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Switch to tenofovir alafenamide
Switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide
Drug: tenofovir alafenamide
Other Names:
  • Descovy
  • TAF
Active Comparator: Switch to abacavir
Switch from tenofovir disoproxil fumarate (TDF) to abacavir
Drug: abacavir
Other Name: ABC



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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 .

  5. plasma HIV RNA <50c/ml [ Time Frame: 96 weeks ]
    HIV-RNA suppression rate <50 ABC versus TAF at week 48 and 96.

  6. Adverse events [ Time Frame: 96 weeks ]
    Tolerability of TAF versus ABC, defined in terms of adverse events (%).

  7. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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):

  1. Accelerated eGFR decline: mean of > 3 mL/min/year since start TDF after ≥5 years of TDF exposure.
  2. Confirmed eGFR < 70 mL/min in patients with baseline eGFR > 90 mL/min at start of TDF.
  3. 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).

Exclusion Criteria:

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.


Information from the National Library of Medicine

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


Contacts
Contact: Ingeborg Wijting, MD 0031107040704 i.wijting@erasmusmc.nl
Contact: bart rijnders, MD PhD 0031107033510 b.rijnders@erasmusmc.nl

Locations
Netherlands
MC Slotervaart Not yet recruiting
Amsterdam, Netherlands, 1066EC
Contact: Saskia Vrouenraets, MD, PhD    0205129333    saskia.vrouenraets@slz.nl   
OLVG Not yet recruiting
Amsterdam, Netherlands, 1091AC
Contact: Guido van den Berk, MD, PhD    0205999111    g.e.l.vandenberk@olvg.nl   
Erasmus MC Recruiting
Rotterdam, Netherlands, 3000CA
Contact: ingeborg wijting, MD    0031107040704    i.wijting@erasmusmc.nl   
Contact: bart rijnders, MD PhD    0031107033510    b.rijnders@erasmusmc.nl   
Maasstad ziekenhuis Not yet recruiting
Rotterdam, Netherlands, 3079DZ
Contact: Anna Roukens, MD, PhD    0102911911    roukensa@maasstadziekenhuis.nl   
Sponsors and Collaborators
Erasmus Medical Center
Gilead Sciences
Investigators
Study Director: Bart Rijnders, MD PhD Erasmus MC

Responsible Party: Bart Rijnders, principle investigator, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02957864     History of Changes
Other Study ID Numbers: NL55668.078.16
First Posted: November 8, 2016    Key Record Dates
Last Update Posted: November 8, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Renal Insufficiency, Chronic
Renal Insufficiency
Drug-Related Side Effects and Adverse Reactions
Kidney Diseases
Urologic Diseases
Chemically-Induced Disorders
Tenofovir
Abacavir
Dideoxynucleosides
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Antimetabolites