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

NCT02042001 | Completed Phase 4 DMC

• 1 other identifier: IN-IT-264-1331
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 5

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.

Conditions

Impaired Cognition; Depression/Anxiety; Poor Quality Sleep; Quality of Life; HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• Composite neuropsychiatric/neurocognitive

  Proportion of patients with improvement in either one of the previous binary end-point (composite end-point)

  24 weeks

Secondary Outcomes (7)

• Symptoms

  24 weeks

• Quality of Life

  24 weeks

• Cognitive failure

  24 weeks

• Viral suppression

  12 weeks

• Viral failure

  12 weeks

Other Outcomes (2)

• Resistance

  12 & 24 weeks

• Immunological response

  12 & 24 weeks

Study Arms (2)

Immediate Switch

EXPERIMENTAL

Immediate switch to TDF/FTC/RPV

Drug: Immediate switch to TDF/FTC/RPV

Deferred Switch

ACTIVE COMPARATOR

Switch to TDF/FTC/RPV after 24 weeks

Drug: Switch to TDF/FTC/RPV after 24 weeks

Interventions

Immediate switch to TDF/FTC/RPV DRUG

Also known as: Eviplera (r)

Immediate Switch

Switch to TDF/FTC/RPV after 24 weeks DRUG

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

Also known as: Eviplera(r)

Deferred Switch

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Ospedaliera San Gerardo di Monza: lead
• Gilead Sciences: collaborator

Study Sites (5)

Clinic of Infectious Diseases, AO San Gerardo

Monza, MB, 20900, Italy

Location

Spedali Civili - University of Brescia

Brescia, Italy

Location

Clinica di Malattie Infettive, Ospedale San Martino

Genova, Italy

Location

AO San Paolo - University of Milan

Milan, Italy

Location

Ospedale Amedeo di Savoia - University of Turin

Torino, Italy

Location

MeSH Terms

Conditions

Cognition Disorders; Depression; Anxiety Disorders

Condition Hierarchy (Ancestors)

Neurocognitive Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Giuseppe Lapadula, MD, PhD

  AO San Gerardo of Monza

  PRINCIPAL INVESTIGATOR

• Andrea Gori, MD

  AO San Gerardo of Monza

  STUDY DIRECTOR

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: M.D. Ph.D

Study Record Dates

• First Submitted: January 20, 2014
• First Posted: January 22, 2014
• Study Start: July 1, 2015
• Primary Completion: July 3, 2017
• Study Completion: January 15, 2018
• Last Updated: July 5, 2018

Record last verified: 2014-08

Locations

IT (5)