NCT02957864

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
80

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Oct 2016

Longer than P75 for phase_4

Geographic Reach
1 country

5 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2016

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

November 4, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 8, 2016

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2020

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2020

Completed
Last Updated

January 28, 2020

Status Verified

January 1, 2020

Enrollment Period

3.7 years

First QC Date

November 4, 2016

Last Update Submit

January 27, 2020

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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.

    48 weeks

Secondary Outcomes (7)

  • Time to recovery of renal dysfunction

    96 weeks

  • Slope of eGFR-decline/increase

    96 weeks

  • Recovery of proteinuria

    96 weeks

  • Recovery of proximal tubular dysfunction

    96 weeks

  • plasma HIV RNA <50c/ml

    96 weeks

  • +2 more secondary outcomes

Study Arms (2)

Switch to tenofovir alafenamide

EXPERIMENTAL

Switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide

Drug: tenofovir alafenamide

Switch to abacavir

ACTIVE COMPARATOR

Switch from tenofovir disoproxil fumarate (TDF) to abacavir

Drug: abacavir

Interventions

Also known as: Descovy, TAF
Switch to tenofovir alafenamide
Also known as: ABC
Switch to abacavir

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • HIV-positive documented by ELISA or Western Blot or plasma HIV-RNA \> 1000 copies/mL.
  • 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.
  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Ziekenhuis Rijnstate

Arnhem, Gelderland, Netherlands

RECRUITING

MC Slotervaart

Amsterdam, 1066EC, Netherlands

RECRUITING

OLVG

Amsterdam, 1091AC, Netherlands

NOT YET RECRUITING

Erasmus MC

Rotterdam, 3000CA, Netherlands

RECRUITING

Maasstad ziekenhuis

Rotterdam, 3079DZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, ChronicAcquired Immunodeficiency SyndromeDrug-Related Side Effects and Adverse Reactions

Interventions

tenofovir alafenamideemtricitabine tenofovir alafenamideabacavir

Condition Hierarchy (Ancestors)

Renal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsHIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesChemically-Induced Disorders

Study Officials

  • Bart Rijnders, MD PhD

    Erasmus Medical Center

    STUDY DIRECTOR

Central Study Contacts

Ingeborg Wijting, MD

CONTACT

bart rijnders, MD PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
principle investigator

Study Record Dates

First Submitted

November 4, 2016

First Posted

November 8, 2016

Study Start

October 1, 2016

Primary Completion

June 1, 2020

Study Completion

September 1, 2020

Last Updated

January 28, 2020

Record last verified: 2020-01

Data Sharing

IPD Sharing
Will not share

Locations