Decrease of Neuropsychiatric Side Effects After Switching From Atripla to Eviplera (DeepSwitch)

Decrease of Neuropsychiatric and Neurocognitive Side Effects Prevalence

The aim of this prospective, open label study is to check for differences in neuropsychiatric and neurocognitive measurements among patients that will be switched from Atripla to Eviplera among 40 patients.

Study Overview

• Status: Terminated
• Conditions: HIV
• Intervention / Treatment: Drug: Tenofovir disoproxil/emtricitabine/rilpivirine; Drug: Tenofovir disoproxil/emtricitabine/efavirenz

Detailed Description

40 patients on Atripla for at least 12 weeks with undetectable HIV-1 viral load will be randomly assigned to one of two groups in a ratio of 1:1: half of the patients will be switched to Eviplera and half will remain on Atripla. Neuropsychiatric symptoms will be evaluated using specific questionnaires (anxiety and depression scales, sleeping quality scale, etc) and neurocognitive functions will be assessed using standard tests (Trail A and B, memory tests, etc). Patient satisfaction will be assessed using a visual analog scale. Treatment efficacy will be evaluated by measuring the rate of patients with HIV vilral load under 50 copies/mL.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to understand and sign a written informed consent form
• Receiving Atripla continuously for >12 weeks preceding the screening visit
• Plasma HIV-1 RNA levels (at least in two measurements) <50 copies/mL for >8 weeks prior to the screening visit and at the screening visit
• Atripla or Truvada + Efavirenz was the first antiretroviral regimen and no HIV-1 RNA > 50 copies/mL measured at two consecutive time points after first achieving HIV RNA <50 copies/mL
• Had a genotype prior to starting study drugs and no known resistance to any of the study drugs
• Normal ECG
• Hepatic transaminase (AST and ALT) <5 X upper limit of normal (ULN)
• Total bilirubin <1.5 mg/dL
• eGFR > 60 mL/min
• Neutrophil count > 1000/mm3, platelets >50,000/mm3. Haemoglobin > 8.5 g/dL
• Age > 18
• Males and Females of childbearing potential must have agreed to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be nonheterosexually active, practice sexual abstinence, or have a vasectomized partner) from screening throughout the duration of the study period and for 60 days following the last dose of study drug.

Exclusion Criteria:

• Subjects with known allergy to one of the study drugs
• AIDS defining event diagnosed within 21 days prior to screening
• Females who are pregnant or breast feeding
• Acute hepatitis diagnosed within 21 days prior to screening
• Subjects receiving drug treatment for HCV or subjects anticipated to receive treatment for HCV during the course of the study
• Implanted defibrillator or pacemaker
• Current alcohol or drug abuse judged by the investigator to potentially interfere with subject adherence
• Participation in another interventional trial
• Ongoing therapy or anticipated need to initiate drugs during the study that are contraindicated or not recommended for use with study drugs (Carbamazepine, Dexamethasone, Esomeprazole, Fosphenytoin, Lansoprazole, Omeprazole, Oxcarbazepine, Pantoprazole, Phenobarbital, Phenytoin, Piperaquine, Primnidone, Rabeprazole, Rifabutin, Rifampin, Rifapentine, St John's Wort
• Any Severe Psychiatric disease that judged by the investigator to potentially interfere with subject adherence to protocol or to drugs or that may interfere with study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eviplera (complera); Tab eviplera QD	Drug: Tenofovir disoproxil/emtricitabine/rilpivirine; Other Names: eviplera, complera
Active Comparator: atripla; Tab Atripla QD	Drug: Tenofovir disoproxil/emtricitabine/efavirenz; Other Names: Atripla

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
depression (questionaire)	PHQ which is a validated questionaire for depression	12 month
anxiety (questionaire)	STAI which is a validated questionaire for anxiety	12 month
sleeping quality (questionaire)	a validated questionaire	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hopkins Verbal Learning Test - Revised (test result in numbers)	a validated test for memory testing	12 month
Satisfaction (scale)	Visual Analogue Scale (VAS)	12 month
viral load (copies/mL)	efficacy of treatment in keeping undetectable viral load	24 month
color trail test - 2 parts (test result in numbers)	a line drawing test which connects points in a certain order. It serves as a general neurocognitive function test	12 month
grooved pegboard test (test result in numbers)	a specific test which serves as a general neurocognitive function test and was validated in HIV patients	12 month
clock drawing test (test result in numbers)	a general test for dementia	12 month
CD4 cell count (number of cells per mm3)	efficacy of treatment in keeping CD4 count from falling after intervention	12 month

Collaborators and Investigators

• Sponsor: Sheba Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): December 21, 2016
• Study Completion (Actual): December 21, 2016

Study Registration Dates

• First Submitted: May 10, 2015
• First Submitted That Met QC Criteria: May 13, 2015
• First Posted (Estimate): May 18, 2015

Study Record Updates

• Last Update Posted (Actual): April 27, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Emtricitabine; Efavirenz; Rilpivirine
• Other Study ID Numbers: SHEBA-14-1462-IL-SMC