This study aims to investigate the effect of switching from Atripla® to Eviplera® on neurocognitive performances (neurocognitive testing) and imaging (functional MRI scanning) in virologically suppressed HIV-infected patients and stable on atripla.
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
- Viral infectious disorders
- Cognitive and attention disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Neurocognitive composite score on 12 weeks after switching from Atripla to
Eviplera corrected for the baseline-level and compared to a controlgroup of
patients on Atripla
Secondary outcome
1) neuronal activity measured by functional MRI on 12 weeks after switching
from Eviplera to Atripla corrected for baseline-level and compared to a control
group of patients on Atripla
2) correlation between changes in NP-score and fMRI-data after 12 weeks of
Eviplera, measured with a reliability coefficient
3) change in SF-36 total score (health-related quality of life) after 12 weeks
of Eviplera
4) change in HADS-score (emotional functioning) and USER-P-score
(participation) after 12 weeks of Eviplera
5) correlation between drug levels and changes in neurocognitive performance
measured by NP-testing and fMRI
6) the usefulness of PROMIS instruments in HIV research
7) the correlation between NFL plasma levels and NP-score
Background summary
Efavirenz, an antiretroviral drug used for the treatment of human
immunodeficiency virus 1 (HIV-1) infections, is known for its neurological and
psychiatric adverse events. Efavirenz is part of Atripla®, a single tablet
regimen (STR), currently the most perscribed antiretroviral drug in the
Netherlands. Recently, a new STR has become available, Eviplera® containing a
successor of Efavirenz, named Rilpivirin. It has been shown in the phase-3 ECHO
and Thrive studies that Atripla® as well as Eviplera® have excellent and
comparable antiretroviral efficacy in naive HIV-infected patients. Furthermore,
data from these studies have shown that Eviplera® was associated with fewer
neurological and psychiatric adverse events than Atripla® over 48 weeks.
However, this was only patient reported adverse events, not neuropsychological
evaluation. Moreover, there might be a bias in these kind of switch studies due
to the fact that those patients who switch will mostly regard their new
combination better than the old one. Contrary, data on the long term impact of
Efavirenz on neuropsychological performance and symptoms are conflicting.
Finally, is there a large goup of patients stable on atripla without
complaints. With newer drugs becoming available and efavirenz becoming generic,
there is disscussion whether to switch those stable patients or to keep them on
efavirenz. To gain more insight and guide this decision, this study will be
performed.
Study objective
This study aims to investigate the effect of switching from Atripla® to
Eviplera® on neurocognitive performances (neurocognitive testing) and imaging
(functional MRI scanning) in virologically suppressed HIV-infected patients and
stable on atripla.
Study design
Randomized Controlled Trial
Intervention
At start of the study patients will be randomly assigned to the intervention
group or the control group. The intervention group will switch to open-label
FTC/RPV/TDF STR (Eviplera®), the control group shall continue with Atripla®. At
baseline and at week 12, a standard set of neuropsychological tests will be
performed together with brain functional magnetic resonance imaging (fMRI) with
the purpose to correlate neurocognitive improvement to functional imaging.
Furthermore, drug levels of both drugs will be measured. Moreover, similar to
routine outpatients care, 2 and 4 weeks after switch, routine laboratory
measurements and outpatients care will be provided to the intervention group.
Study burden and risks
Eviplera is a medicin proven to be safe, and registered for the treatment of
HIV. Like Atripla, it is to be taken once daily. However, unlike Atripla,
Eviplera has to be taken during the meal. This is a change in routine and thus
requires an effort on the patient's side. Both the neuropsychological testing
and the functional MRI-scan are safe procedures with a minimal risk of side
effects. The few venapunctions pose a minimal burden and risk (haematoma's,
local infection). Patients will have to come to the hospital for three visits,
or five when they are in the intervention group. Two study-visits are of longer
duration, approximately three hours (fMRI and neuropsychological testing).
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
- Male, between 25 and 50 years
- HIV-1 RNA < 50 copies/mL on last routine measurement during outpatient clinic
- on EFV/FTC/TDF STR (Atripla) continuously for *6 months preceding the screening visit
- Have a HIV genotype prior to starting cART with EFV/FTC/TDF STR with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y
- Negative TPHA or VDRL < 12 months prior to or at the screening visit
- no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. Neth J Med 2011)
- No subjective neurocognitive complaints in the preceding 12 months
- willingness to take Eviplera together with food according to the manufacturer*s prescriptions.
- Estimated glomerular filtration rate *50 mL/min (Cockcroft-Gault formula) on last routine measurement during outpatient clinic
- able to understand and comply to study procedures and to provide written informed consent
Exclusion criteria
- Insufficient fluency in written and spoken Dutch
- Proven major depression through psychiatric consultation within the past year or on anti-depressant drugs (SSRI or TCA)
- Active or known from medical history past CNS opportunistic infections
- History of proven neurologic disease (e.g. multiple sclerosis, brain tumor, cerebrovasculair event, etc)
- Active psychiatric disorders classified according to the DSM V criteria
- History or evidence of alcohol or drug abuse defined according to DSM V criteria
- TSH not within normal reference values on last routine measurement during outpatient clinic
- Contraindications for undergoing an MRI; a pacemaker or metallic devices/foreign bodies in situ, proven claustrophobia.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-004297-42-NL |
| ClinicalTrials.gov | NCT02308332 |
| CCMO | NL52694.041.15 |