Effects of Maraviroc vs. Efavirenz on CD4/CD8 Ratio (MeritRate)

September 12, 2023 updated by: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

The Effects of Maraviroc Versus Efavirenz in Combination With Zidovudine/Abacavir on the CD4/CD8 Ratio in Treatment-naïve HIV-infected Individuals

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

721

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

All patients analysed in the Merit trial (Cooper, JAIDS 2010)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID

Maraviroc (UK-427,857) 300 mg once daily added to Zidovudine/Lamivudine (300 mg/150 mg twice daily).

Following a review of the interim analysis data, the DSMB recommended to terminate the UK-427,857 300 mg QD arm based on pre-specified protocol non-inferiority criteria not being met for the QD arm versus efavirenz
Drug: Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID
maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily
Active Comparator: Efavirenz QD + Zidovudine/Lamivudine BID
Efavirenz (600 mg once daily) added to Zidovudine/Lamivudine (300 mg/150 mg twice daily
Drug: Efavirenz QD + Zidovudine/Lamivudine BID
efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily)
Experimental: Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine BID
Maraviroc (UK-427,857) 300 mg twice daily added to Zidovudine/Lamivudine (300 mg/150 mg twice daily)
Drug: Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QD
maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change From Baseline in CD4/CD8 ratio
Time Frame: From baseline to week 120
From baseline to week 120

Secondary Outcome Measures

Outcome Measure
Time Frame
Change From Baseline in CD4/CD8 ratio
Time Frame: From baseline to week 120
From baseline to week 120
Change From Baseline in CD8+ T cells
Time Frame: From baseline to week 120
From baseline to week 120

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 15, 2014

Primary Completion (Actual)

November 5, 2016

Study Completion (Actual)

March 7, 2017

Study Registration Dates

First Submitted

April 7, 2017

First Submitted That Met QC Criteria

June 4, 2017

First Posted (Actual)

June 6, 2017

Study Record Updates

Last Update Posted (Actual)

September 13, 2023

Last Update Submitted That Met QC Criteria

September 12, 2023

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MeritRate

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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