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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by Azienda Ospedaliera San Gerardo di Monza
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Giuseppe Lapadula, Azienda Ospedaliera San Gerardo di Monza
ClinicalTrials.gov Identifier:
NCT02042001
First received: January 20, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

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 EFV-based regimen 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 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 (12 weeks) switch to TDF/FTC/RPV. Neurocognitive and neuropsychiatric tests will be repeated after 12 and 24 weeks of follow-up and variations will be compared between groups.


Condition Intervention Phase
Impaired Cognition
Depression/Anxiety
Poor Quality Sleep
Quality of Life
HIV-1 Infection
Drug: Immediate switch to TDF/FTC/RPV
Drug: Switch to TDF/FTC/RPV after 12 weeks
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Randomized Controlled Trial of Switch to Tenofovir Disoproxil Fumarate/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Versus Continue Efavirenz (EFV)-Based Treatment Among Virologically Suppressed, HIV-1 Infected Subjects With Mild or Asymptomatic EFV-related Neurocognitive or Neuropsychological Side Effects

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliera San Gerardo di Monza:

Primary Outcome Measures:
  • Neuropsychiatric side effects [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    - 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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with improvement in either one of the previous binary end-point (composite end-point)


Secondary Outcome Measures:
  • Symptoms [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with self-reported improvement in treatment-related symptoms

  • Quality of Life [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with self-reported improvement in quality of life

  • Cognitive failure [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with improvement in Cognitive Failure Questionnaire

  • Viral suppression [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with HIV-RNA <50 copies/ml after 12 weeks of treatment (ITT-M=F)

  • Viral failure [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with HIV-RNA <400 copies/ml after 12 weeks (ITT-M=F)

  • Virological efficacy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with HIV-RNA <50 copies/ml after 24 weeks (ITT-M=F)

  • Safety & Tolerability [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Proportion of patients discontinuing treatment for intolerance to study drugs or due to side effects


Other Outcome Measures:
  • Resistance [ Time Frame: 12 & 24 weeks ] [ Designated as safety issue: No ]
    Number of patients with genotypic resistance at failure

  • Immunological response [ Time Frame: 12 & 24 weeks ] [ Designated as safety issue: No ]
    Change From Baseline in CD4+ and CD8+ T-Lymphocyte Cell Counts at Weeks 12 and 24


Estimated Enrollment: 90
Study Start Date: April 2014
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Immediate Switch
Immediate switch to TDF/FTC/RPV
Drug: Immediate switch to TDF/FTC/RPV
Other Name: Eviplera (r)
Active Comparator: Deferred Switch
Switch to TDF/FTC/RPV after 12 weeks
Drug: Switch to TDF/FTC/RPV after 12 weeks
Patients will continue current EFV-containing regimen up to week 12 and then will be switched to TDF/FTC/RPV
Other Name: Eviplera(r)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years old and ability to sign informed consent
  • Continuative treatment with EFV in combination with TDF/FTC or abacavir/lamivudine (ABC/3TC) 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02042001

Contacts
Contact: Giuseppe Lapadula, MD, PhD +39 039 233 9320 g.lapadula@hsgerardo.org
Contact: Andrea Gori, MD +39 039 233 9313 andrea.gori@unimib.it

Locations
Italy
Clinic of Infectious Diseases, AO San Gerardo
Monza, MB, Italy, 20900
Clinica di Malattie Infettive, Ospedale San Martino Not yet recruiting
Genova, Italy
Principal Investigator: Antonio Di Biagio         
AO San Paolo - University of Milan Not yet recruiting
Milan, Italy
Principal Investigator: Antonella d'Arminio Monforte, Prof.         
Ospedale San Raffaele - Università Vita-Salute Not yet recruiting
Milan, Italy
Principal Investigator: Antonella Castagna         
Principal Investigator: Adriano Lazzarin, Prof         
Policlinico Gemelli - Catholic University of Rome Not yet recruiting
Roma, Italy
Principal Investigator: Simona Digiambenedetto, MD, PhD         
Ospedale Amedeo di Savoia - University of Turin Not yet recruiting
Torino, Italy
Principal Investigator: Stefano Bonora, MD         
Sponsors and Collaborators
Azienda Ospedaliera San Gerardo di Monza
Gilead Sciences
Investigators
Principal Investigator: Giuseppe Lapadula, MD, PhD AO San Gerardo of Monza
Study Director: Andrea Gori, MD AO San Gerardo of Monza
  More Information

No publications provided

Responsible Party: Giuseppe Lapadula, M.D. Ph.D, Azienda Ospedaliera San Gerardo di Monza
ClinicalTrials.gov Identifier: NCT02042001     History of Changes
Other Study ID Numbers: IN-IT-264-1331
Study First Received: January 20, 2014
Last Updated: January 20, 2014
Health Authority: Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Depression
Behavioral Symptoms

ClinicalTrials.gov processed this record on September 16, 2014