search
Back to results

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) (DETOX)

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Symtuza® (TAF/FTC/DRV/c)
ABC/3TC/DTG + Symtuza® (TAF/FTC/DRV/c)
Sponsored by
Fundacion SEIMC-GESIDA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital Puerta de Hierro
  • Hospital Univ. 12 de Octubre
  • H. Univ. Príncipe de Asturias
  • Hospital Fundación Jimenez Diaz
  • Hospital Infanta Leonor
  • Hospital Universitario La Paz

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1

Arm 2

Arm Description

Patients who postpone switching from ABC/3TC/DTG to Symtuza® (TAF/FTC/DRV/c) four weeks

Patients who switch from ABC/3TC/DTG to Symtuza® (TAF/FTC/DRV/c) during the baseline visit

Outcomes

Primary Outcome 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
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 Outcome 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
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
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
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
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
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
Virologic failure is defined as the presence of two consecutive HIV viral loads ≥ 50 copies/mL.

Full Information

First Posted
September 8, 2018
Last Updated
June 20, 2022
Sponsor
Fundacion SEIMC-GESIDA
Collaborators
Janssen-Cilag, S.A.
search

1. Study Identification

Unique Protocol Identification Number
NCT03685500
Brief Title
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)
Acronym
DETOX
Official Title
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
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
December 4, 2018 (Actual)
Primary Completion Date
June 25, 2020 (Actual)
Study Completion Date
June 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion SEIMC-GESIDA
Collaborators
Janssen-Cilag, S.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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)
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A phase IV, multicentre, randomised, open-label, pilot clinical trial.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
78 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Active Comparator
Arm Description
Patients who postpone switching from ABC/3TC/DTG to Symtuza® (TAF/FTC/DRV/c) four weeks
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
Patients who switch from ABC/3TC/DTG to Symtuza® (TAF/FTC/DRV/c) during the baseline visit
Intervention Type
Drug
Intervention Name(s)
Symtuza® (TAF/FTC/DRV/c)
Intervention Description
Treatment with TAF/FTC/DRV/c during 8 weeks since randomized
Intervention Type
Drug
Intervention Name(s)
ABC/3TC/DTG + Symtuza® (TAF/FTC/DRV/c)
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
week 4
Secondary Outcome Measure Information:
Title
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
Description
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
Time Frame
week 4
Title
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
Description
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
Time Frame
week 4
Title
Changes in the severity of neuropsychiatric symptoms potentially associated with the use of ABC/3TC/DTG after switching to TAF/FTC/DRV/c
Description
To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the ACTG adverse effects scale
Time Frame
Week 4 and 8 after switching to TAF/FTC/DRV/c
Title
Changes in the severity of neuropsychiatric symptoms potentially associated with the use of ABC/3TC/DTG after switching to TAF/FTC/DRV/c
Description
To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the Pittsburg sleep quality index (PSQI)
Time Frame
Week 4 and 8 after switching to TAF/FTC/DRV/c
Title
Proportion and severity of neuropsychiatric symptoms potentially associated with the use of ABC/3TC/DTG after switching to TAF/FTC/DRV/c
Description
To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the hospital anxiety and depression scale.
Time Frame
Week 4 and 8 after switching to TAF/FTC/DRV/c
Title
Percentage of virologic failure after switching antiretroviral therapy from ABC/3TC/DTG to TAF/FTC/DRV/c
Description
Virologic failure is defined as the presence of two consecutive HIV viral loads ≥ 50 copies/mL.
Time Frame
Week 8 after switching to TAF/FTC/DRV/c

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Hospital Puerta de Hierro
City
Majadahonda
State/Province
Madrid
Country
Spain
Facility Name
Hospital Univ. 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
H. Univ. Príncipe de Asturias
City
Madrid
Country
Spain
Facility Name
Hospital Fundación Jimenez Diaz
City
Madrid
Country
Spain
Facility Name
Hospital Infanta Leonor
City
Madrid
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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)

We'll reach out to this number within 24 hrs