Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03178084 |
| Other study ID # |
MeritRate |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
October 15, 2014 |
| Est. completion date |
March 7, 2017 |
Study information
| Verified date |
June 2017 |
| Source |
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
A low CD4/CD8 ratio is considered a surrogate marker of immunosenescence and is an
independent predictor of non-AIDS-related morbidity and mortality. Given the strong clinical
implications the impact of different regimens on the CD4/CD8 ratio recovery needs to be
analyzed. The MERIT study is a completed a randomized, double-blind, multicenter phase
IIb/III study with an open-label extension phase (240-week follow-up) to assess the efficacy
of zidovudine/lamivudine in combination with maraviroc (MVC) or efavirenz (EFV) in
treatment-naïve patients. Anonymised patient level data of the MERIT trial to compare the
trajectories of the CD4/CD8 ratio of participants treated with maraviroc vs. efavirenz will
be used.
Description:
The Merit study was a randomized, double-blind, active-comparator multicenter, phase IIb/III
study, treatment- naive patients (aged at least 16 years) with R5 HIV-1, and with plasma
viral load (HIV-1 RNA) above 2000 copies/ml, who received MVC 300mg q.d., MVC 300mg b.i.d.,
or EFV 600mg q.d., each in combination with ZDV/3TC 300 mg/150mg b.i.d. Key exclusion
criteria included prior treatment with EFV, ZDV, 3TC, or any antiretroviral for more than 14
days at any time, and evidence of resistance to EFV, ZDV, or 3TC, as indicated by the
presence of at least one nucleoside-associated mutations conferring resistance to ZDV, or
phenotypic resistance to ZDV, at least one mutation conferring resistance to 3TC or
phenotypic resistance to 3TC, or at least one mutation responsible for EFV resistance or
phenotypic resistance to EFV.
Following a planned analysis at week 16, the MVC q.d. arm was discontinued for not meeting
prespecified efficacy criteria, and the study continued with two treatment arms. The sponsor
was unblinded at the 48-week analysis time point, but the investigators and patients remained
blinded until the 96-week analysis. The study was then fully unblinded following the last
patient's 96-week visit, and patients were enrolled in a nominal 3-year open-label phase.
Efficacy and safety data from the 240-week (nominal 5-year) study duration have been recently
published (Cooper D. et al, AIDS 2014).
The longitudinal data of the Merit study (240-week follow-up) will be analysed. The current
long-term follow-up of the MERIT study, the extensive registry of both AIDS and non-AIDS
clinical events and the randomization to a therapeutic intervention including maraviroc, will
allow to evaluate the effects of maraviroc vs. efavirenz on the CD4/CD8 ratio trajectories.
All randomized subjects included in MERIT will be included in this exploratory post hoc
analysis. For the principal objective, longitudinal changes in CD4 and CD8 counts and in the
CD4/CD8 ratio will be assessed using generalized estimating equations. Interaction terms will
be created to assess whether these changes over time differed significantly between treatment
arms. Kaplan-Meier methods will be used to calculate the rates of CD4/CD8 normalization at
0.4 and 1 cut-offs and cumulative probabilities. Cox proportional hazard models will be used
to compare probabilities of CD4/CD8 normalization by treatment arm.
