A Clinical Trial to Evaluate the Reversibility of Abacavir/Lamivudine/Dolutegravir CNS-Related Neurotoxicity After Switching to Tenofovir/Alafenamide/Emtricitabine/Darunavir/Cobicistat (TAF/FTC/DRV/c)

Overview

A phase IV, multicentre, randomised, open-label, pilot clinical trial to evaluate the Reversibility of abacavir/lamivudine/dolutegravir ( ABC/3TC/DTG) CNS-Related Neurotoxicity After Switching to tenofovir alafenamide/emtricitabine/darunavir/cobicistat (TAF/FTC/DRV/c)

Full Title of Study: “Phase IV, Open Label, Randomized, Clinical Trial to Evaluate the Reversibility of Abacavir/Lamivudine/Dolutegravir CNS-Related Neurotoxicity After Switching to Tenofovir Alafenamide/Emtricitabine/Darunavir/Cobicistat”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 15, 2019

Detailed Description

The investigators estimate that 55 participants will need to be included per group, 110 patients in total, to demonstrate the benefit of switching ABC/3TC/DTG to TAF/FTC/DRV/c

Interventions

  • Drug: Symtuza® (TAF/FTC/DRV/c)
    • Treatment with TAF/FTC/DRV/c during 8 weeks since randomized
  • Drug: ABC/3TC/DTG + Symtuza® (TAF/FTC/DRV/c)
    • Patients continuing on treatment with DTG/3TC/ABC after the randomization for 4 weeks, and then switch to TAF/FTC/DRV/c for 8 weeks

Arms, Groups and Cohorts

  • Active Comparator: Arm 1
    • Patients who postpone switching from ABC/3TC/DTG to Symtuza® (TAF/FTC/DRV/c) four weeks
  • Experimental: Arm 2
    • Patients who switch from ABC/3TC/DTG to Symtuza® (TAF/FTC/DRV/c) during the baseline visit

Clinical Trial Outcome Measures

Primary Measures

  • Proportion of patients who self-reported insomnia, between HIV-suppressed patients who continue ABC/3TC/DTG and those who switched to TAF/FTC/DRV/c
    • Time Frame: week 4
    • To compare, between the two arms of the study, changes in the percentage and in the severity of neuropsychiatric symptoms compiled using the Pittsburgh sleep quality index (PSQI). The PSQI contains 19 questions in total. These questions are combined to form seven areas with their corresponding score, each of which shows a range between 0 and 3 points. In all cases, a score of “0″ indicates ease, while a score of 3 indicates medium difficulty, within their respective area. The score of the seven areas is finally added for a global score, which ranges from 0 to 21 points. “0″ indicates ease of sleep and “21″ severe difficulty in all areas

Secondary Measures

  • Changes in the severity of neuropsychiatric symptoms, between HIV-suppressed patients who continue ABC/3TC/DTG and those who switched to TAF/FTC/DRV/c
    • Time Frame: week 4
    • To compare, between the two arms of the study, changes in the percentage and in the severity of neuropsychiatric symptoms compiled using the ACTG adverse effects scale. Researchers will specifically ask the patient about eleven adverse effects at each visit. Each adverse effect will be documented and graduated, according to the criteria established in the “AIDS Clinical Trials Group (ACTG) Division of AIDS scale (2014)”. Each adverse effect will be assigned a score between 0 and 3 points. The Score will include the individual scores for each of the eleven adverse effects collected, as well as the sum of all the individual scores presented by each patient at each study visit
  • Changes in the severity of neuropsychiatric symptoms, between HIV-suppressed patients who continue ABC/3TC/DTG and those who switched to TAF/FTC/DRV/c
    • Time Frame: week 4
    • To compare, between the two arms of the study, changes in the percentage and in the severity of neuropsychiatric symptoms compiled using the hospital anxiety and depression scale. The scale includes 14 questions to evaluate the presence of depressive symptoms during the last week. Each question contains four answers with score between 0 and 3 points. To obtain the results of the questionnaire, the researcher must add the score obtained in the 7 questions of anxiety on the one hand and the 7 questions of depression on the other
  • Changes in the severity of neuropsychiatric symptoms potentially associated with the use of ABC/3TC/DTG after switching to TAF/FTC/DRV/c
    • Time Frame: Week 4 and 8 after switching to TAF/FTC/DRV/c
    • To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the ACTG adverse effects scale
  • Changes in the severity of neuropsychiatric symptoms potentially associated with the use of ABC/3TC/DTG after switching to TAF/FTC/DRV/c
    • Time Frame: Week 4 and 8 after switching to TAF/FTC/DRV/c
    • To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the Pittsburg sleep quality index (PSQI)
  • Proportion and severity of neuropsychiatric symptoms potentially associated with the use of ABC/3TC/DTG after switching to TAF/FTC/DRV/c
    • Time Frame: Week 4 and 8 after switching to TAF/FTC/DRV/c
    • To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the hospital anxiety and depression scale.
  • Percentage of virologic failure after switching antiretroviral therapy from ABC/3TC/DTG to TAF/FTC/DRV/c
    • Time Frame: Week 8 after switching to TAF/FTC/DRV/c
    • Virologic failure is defined as the presence of two consecutive HIV viral loads ≥ 50 copies/mL.

Participating in This Clinical Trial

Inclusion Criteria

  • Patient ≥ 18 years of age diagnosed with HIV using conventional serology techniques.
  • Current antiretroviral therapy with ABC/3TC/DTG for at least 4 weeks.
  • HIV viral load < 50 copies/mL for at least 24 weeks prior to signing the consent form (confirmed by two assays at least 12 weeks apart with viremia < 50 copies/mL between both). If the patient has a recent routine blood test available (≤ 4 weeks) that includes determining HIV viral load, these results may be used for the screening visit. If this test is not available, or the test is more than four weeks old, viral load will be determined on the day of screening in order to confirm that the patient meets this criterion.
  • A positive screening test for sleep disorders detected using the sleep quality index (Pittsburgh ).

Exclusion Criteria

  • Determination of at least one HIV viral load ≥ 50 copies/mL in the last 12 weeks.
  • Allergy, intolerance or existence of resistance mutations to any of the components of TAF/FTC/DRV/c.
  • History of active CNS infections.
  • Active psychosis, major depression with psychotic symptoms or autolytic ideation.
  • Dementia or mental retardation.
  • Drug use with a diagnosis of abuse or dependence according to DSM-5 criteria.
  • Illnesses that may interfere with the study procedures.
  • Inability to complete any of the study procedures.
  • Pregnant or nursing women, as well as women of childbearing age who do not agree to use an adequate birth control method.
  • Patient with documented intolerance or hypersensitivity to the study medication, or who has a contraindication to use it, according to the technical data sheet

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 100 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Fundacion SEIMC-GESIDA
  • Collaborator
    • Janssen-Cilag, S.A.
  • Provider of Information About this Clinical Study
    • Sponsor

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.