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

Quality of Life Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02042001
• Other study ID #: IN-IT-264-1331
• Status: Completed
• Phase: Phase 4
• Start date: July 1, 2015
• Est. completion date: January 15, 2018

Study information

• Verified date: August 2014
• Source: Azienda Ospedaliera San Gerardo di Monza
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: January 15, 2018
• Est. primary completion date: July 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Depression/Anxiety
• HIV-1 Infection
• Impaired Cognition
• Poor Quality Sleep
• Quality of Life

Intervention

Drug:
• Immediate switch to TDF/FTC/RPV

• Switch to TDF/FTC/RPV after 24 weeks
Patients will continue current EFV-containing regimen up to week 24 and then will be switched to TDF/FTC/RPV

Locations

Country	Name	City	State
Italy	Spedali Civili - University of Brescia	Brescia
Italy	Clinica di Malattie Infettive, Ospedale San Martino	Genova
Italy	AO San Paolo - University of Milan	Milan
Italy	Clinic of Infectious Diseases, AO San Gerardo	Monza	MB
Italy	Ospedale Amedeo di Savoia - University of Turin	Torino

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Ospedaliera San Gerardo di Monza	Gilead Sciences

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Resistance	Number of patients with genotypic resistance at failure	12 & 24 weeks
Other	Immunological response	Change From Baseline in CD4+ and CD8+ T-Lymphocyte Cell Counts at Weeks 12 and 24	12 & 24 weeks
Primary	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	24 weeks
Primary	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)	24 weeks
Primary	Composite neuropsychiatric/neurocognitive	Proportion of patients with improvement in either one of the previous binary end-point (composite end-point)	24 weeks
Secondary	Symptoms	Proportion of patients with self-reported improvement in treatment-related symptoms	24 weeks
Secondary	Quality of Life	Proportion of patients with self-reported improvement in quality of life	24 weeks
Secondary	Cognitive failure	Proportion of patients with improvement in Cognitive Failure Questionnaire	24 weeks
Secondary	Viral suppression	Proportion of patients with HIV-RNA <50 copies/ml after 12 weeks of treatment (ITT-M=F)	12 weeks
Secondary	Viral failure	Proportion of patients with HIV-RNA <400 copies/ml after 12 weeks (ITT-M=F)	12 weeks
Secondary	Virological efficacy	Proportion of patients with HIV-RNA <50 copies/ml after 24 weeks (ITT-M=F)	24 weeks
Secondary	Safety & Tolerability	Proportion of patients discontinuing treatment for intolerance to study drugs or due to side effects	24 weeks