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Switching From Efavirenz/Atripla to Rilpivirine Among Patients With Neurocognitive or Neuropsychological Side Effects (SWEAR)

Primary Purpose

Impaired Cognition, Depression/Anxiety, Poor Quality Sleep

Status
Completed
Phase
Phase 4
Locations
Italy
Study Type
Interventional
Intervention
Immediate switch to TDF/FTC/RPV
Switch to TDF/FTC/RPV after 24 weeks
Sponsored by
Azienda Ospedaliera San Gerardo di Monza
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Impaired Cognition

Eligibility Criteria

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

Inclusion Criteria:

  • Age ≥18 years old and ability to sign informed consent
  • Continuative treatment with TDF/FTC/EFV for ≥180 days
  • HIV-1 RNA viral load < 50 copies/mL in two consecutive determinations (including screening)
  • No history of treatment failure and/or evidence of any mutations associated with resistance to NRTI or NNRTI
  • No contraindication to treatment with study drugs

  • Any one of the following conditions:

    (i) Altered scores in depression, quality of sleep or anxiety tests (ii) Alteration in 1 or more domains as assessed by neuropsychological assessment

Exclusion Criteria:

  • Ongoing treatment or predictable need of treatment with proton pump inhibitors
  • New AIDS defining condition diagnosed within the 21 days prior to screening
  • Previous diagnosis of AIDS dementia complex
  • Current alcohol or substance dependence
  • Major psychiatric disorders
  • Decompensated cirrhosis
  • Plasma creatinine >1.2 mg/dl or estimated glomerular filtration rate <60 ml/min (MDRD formula)
  • AST, ALT or plasma bilirubin >3 times upper limit of normal
  • Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing/food requirements

Sites / Locations

  • Clinic of Infectious Diseases, AO San Gerardo
  • Spedali Civili - University of Brescia
  • Clinica di Malattie Infettive, Ospedale San Martino
  • AO San Paolo - University of Milan
  • Ospedale Amedeo di Savoia - University of Turin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Immediate Switch

Deferred Switch

Arm Description

Immediate switch to TDF/FTC/RPV

Switch to TDF/FTC/RPV after 24 weeks

Outcomes

Primary Outcome Measures

Neuropsychiatric side effects
Proportion of patients with improvement in depression, anxiety or quality of sleep scores, evaluated either as a binary (Yes/No) or on a continuous scale
Neurocognitive side effects
- Proportion of patients with improvement in neurocognitive performances in either one of the 7 domains investigated, evaluated either as a binary (Abnormal/Normal) or on a continuous scale (deficit score)
Composite neuropsychiatric/neurocognitive
Proportion of patients with improvement in either one of the previous binary end-point (composite end-point)

Secondary Outcome Measures

Symptoms
Proportion of patients with self-reported improvement in treatment-related symptoms
Quality of Life
Proportion of patients with self-reported improvement in quality of life
Cognitive failure
Proportion of patients with improvement in Cognitive Failure Questionnaire
Viral suppression
Proportion of patients with HIV-RNA <50 copies/ml after 12 weeks of treatment (ITT-M=F)
Viral failure
Proportion of patients with HIV-RNA <400 copies/ml after 12 weeks (ITT-M=F)
Virological efficacy
Proportion of patients with HIV-RNA <50 copies/ml after 24 weeks (ITT-M=F)
Safety & Tolerability
Proportion of patients discontinuing treatment for intolerance to study drugs or due to side effects

Full Information

First Posted
January 20, 2014
Last Updated
July 2, 2018
Sponsor
Azienda Ospedaliera San Gerardo di Monza
Collaborators
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02042001
Brief Title
Switching From Efavirenz/Atripla to Rilpivirine Among Patients With Neurocognitive or Neuropsychological Side Effects
Acronym
SWEAR
Official Title
A Pilot Randomized Controlled Trial of Switch to Tenofovir Disoproxil Fumarate/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Versus Continue TDF/FTC/Efavirenz (EFV) Treatment Among Virologically Suppressed, HIV-1 Infected Subjects With Mild or Asymptomatic EFV-related Neurocognitive or Neuropsychological Side Effects
Study Type
Interventional

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
July 1, 2015 (Actual)
Primary Completion Date
July 3, 2017 (Actual)
Study Completion Date
January 15, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliera San Gerardo di Monza
Collaborators
Gilead Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Despite long-term use in clinical practice, chronic treatment with efavirenz (EFV) has been associated with persistent central nervous system symptoms or mild or even asymptomatic neurocognitive impairment. Whether switching to rilpivirine (RPV) containing regimen is beneficial among patients who experience mild or asymptomatic neurocognitive/neuropsychiatric adverse events during EFV has not been explored yet. The proposed pilot study will examine whether switching from single tablet regimen TDF/FTC/EFV to single tablet regimen TDF/FTC/RPV is associated with neurocognitive/neuropsychiatric improvement among HIV-infected patients with mild/asymptomatic neurocognitive impairment or neuropsychiatric symptoms during EFV-containing antiretroviral treatment. Patients under stable treatment with TDF/FTC/EFV, confirmed HIV-1 RNA viral load < 50 copies/mL and altered scores in depression, quality of sleep or anxiety tests and/or alteration in 1 or more domains as assessed by neuropsychological assessment, will be randomized to immediate or deferred (24 weeks) switch to TDF/FTC/RPV. Neurocognitive and neuropsychiatric tests will be repeated after 12, 24 and 48 weeks of follow-up and variations will be compared between groups.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Impaired Cognition, Depression/Anxiety, Poor Quality Sleep, Quality of Life, HIV-1 Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Immediate Switch
Arm Type
Experimental
Arm Description
Immediate switch to TDF/FTC/RPV
Arm Title
Deferred Switch
Arm Type
Active Comparator
Arm Description
Switch to TDF/FTC/RPV after 24 weeks
Intervention Type
Drug
Intervention Name(s)
Immediate switch to TDF/FTC/RPV
Other Intervention Name(s)
Eviplera (r)
Intervention Type
Drug
Intervention Name(s)
Switch to TDF/FTC/RPV after 24 weeks
Other Intervention Name(s)
Eviplera(r)
Intervention Description
Patients will continue current EFV-containing regimen up to week 24 and then will be switched to TDF/FTC/RPV
Primary Outcome Measure Information:
Title
Neuropsychiatric side effects
Description
Proportion of patients with improvement in depression, anxiety or quality of sleep scores, evaluated either as a binary (Yes/No) or on a continuous scale
Time Frame
24 weeks
Title
Neurocognitive side effects
Description
- Proportion of patients with improvement in neurocognitive performances in either one of the 7 domains investigated, evaluated either as a binary (Abnormal/Normal) or on a continuous scale (deficit score)
Time Frame
24 weeks
Title
Composite neuropsychiatric/neurocognitive
Description
Proportion of patients with improvement in either one of the previous binary end-point (composite end-point)
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Symptoms
Description
Proportion of patients with self-reported improvement in treatment-related symptoms
Time Frame
24 weeks
Title
Quality of Life
Description
Proportion of patients with self-reported improvement in quality of life
Time Frame
24 weeks
Title
Cognitive failure
Description
Proportion of patients with improvement in Cognitive Failure Questionnaire
Time Frame
24 weeks
Title
Viral suppression
Description
Proportion of patients with HIV-RNA <50 copies/ml after 12 weeks of treatment (ITT-M=F)
Time Frame
12 weeks
Title
Viral failure
Description
Proportion of patients with HIV-RNA <400 copies/ml after 12 weeks (ITT-M=F)
Time Frame
12 weeks
Title
Virological efficacy
Description
Proportion of patients with HIV-RNA <50 copies/ml after 24 weeks (ITT-M=F)
Time Frame
24 weeks
Title
Safety & Tolerability
Description
Proportion of patients discontinuing treatment for intolerance to study drugs or due to side effects
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
Resistance
Description
Number of patients with genotypic resistance at failure
Time Frame
12 & 24 weeks
Title
Immunological response
Description
Change From Baseline in CD4+ and CD8+ T-Lymphocyte Cell Counts at Weeks 12 and 24
Time Frame
12 & 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years old and ability to sign informed consent Continuative treatment with TDF/FTC/EFV for ≥180 days HIV-1 RNA viral load < 50 copies/mL in two consecutive determinations (including screening) No history of treatment failure and/or evidence of any mutations associated with resistance to NRTI or NNRTI No contraindication to treatment with study drugs Any one of the following conditions: (i) Altered scores in depression, quality of sleep or anxiety tests (ii) Alteration in 1 or more domains as assessed by neuropsychological assessment Exclusion Criteria: Ongoing treatment or predictable need of treatment with proton pump inhibitors New AIDS defining condition diagnosed within the 21 days prior to screening Previous diagnosis of AIDS dementia complex Current alcohol or substance dependence Major psychiatric disorders Decompensated cirrhosis Plasma creatinine >1.2 mg/dl or estimated glomerular filtration rate <60 ml/min (MDRD formula) AST, ALT or plasma bilirubin >3 times upper limit of normal Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing/food requirements
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giuseppe Lapadula, MD, PhD
Organizational Affiliation
AO San Gerardo of Monza
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andrea Gori, MD
Organizational Affiliation
AO San Gerardo of Monza
Official's Role
Study Director
Facility Information:
Facility Name
Clinic of Infectious Diseases, AO San Gerardo
City
Monza
State/Province
MB
ZIP/Postal Code
20900
Country
Italy
Facility Name
Spedali Civili - University of Brescia
City
Brescia
Country
Italy
Facility Name
Clinica di Malattie Infettive, Ospedale San Martino
City
Genova
Country
Italy
Facility Name
AO San Paolo - University of Milan
City
Milan
Country
Italy
Facility Name
Ospedale Amedeo di Savoia - University of Turin
City
Torino
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

Switching From Efavirenz/Atripla to Rilpivirine Among Patients With Neurocognitive or Neuropsychological Side Effects

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