HIV/AIDSPhase 3MeritRateNCT03178084
Effects of Maraviroc vs. Efavirenz on CD4/CD8 Ratio
A Phase 3 study testing Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID, Efavirenz QD + Zidovudine/Lamivudine BID and Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QD in people with HIV/AIDS, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal.
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID, Efavirenz QD + Zidovudine/Lamivudine BID and Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QD
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 721 participants
- Where
- No sites listed yet
- Study dates
- 15 Oct 2014to 7 Mar 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
All patients analysed in the Merit trial (Cooper, JAIDS 2010)
About this study
Official title: 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.
Read the 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.
- Conditions
- HIV/AIDS
- Being tested
- Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID, Efavirenz QD + Zidovudine/Lamivudine BID, Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QD
- Keywords
- HIV, CD4/CD8 ratio, immune recovery, maraviroc, efavirenz
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BIDDrug
maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily
Efavirenz QD + Zidovudine/Lamivudine BIDDrug
efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily)
Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QDDrug
maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily
| Study group | Role | What they receive |
|---|---|---|
| Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID | Experimental | 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 Receives: Drug: Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID |
| Efavirenz QD + Zidovudine/Lamivudine BID | Active comparator | Efavirenz (600 mg once daily) added to Zidovudine/Lamivudine (300 mg/150 mg twice daily Receives: Drug: Efavirenz QD + Zidovudine/Lamivudine BID |
| Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine BID | Experimental | Maraviroc (UK-427,857) 300 mg twice daily added to Zidovudine/Lamivudine (300 mg/150 mg twice daily) Receives: Drug: Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in CD4/CD8 ratio
Measured: From baseline to week 120
Secondary outcomes (2)
Change From Baseline in CD8+ T cells
Measured: From baseline to week 120
Change From Baseline in CD4/CD8 ratio
Measured: From baseline to week 120
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2017
- Study start15 Oct 2014
- Primary completion5 Nov 2016
- Study completion7 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 721 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03178084
- Sponsor's protocol ID
- MeritRate
- Acronym
- MeritRate
- Status last verified
- Jun 2017
- First submitted
- 7 Apr 2017
- Last updated
- 13 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Maraviroc Versus Efavirenz in Combination With Zidovudine/Abacavir on the CD4/CD8 Ratio in Treatment-naïve HIV-infected Individuals
- ClinicalTrials.gov ID
- NCT03178084
- Acronym / sponsor ID
- MeritRate / MeritRate
- Conditions
- HIV/AIDS
- Keywords
- HIV, CD4/CD8 ratio, immune recovery, maraviroc, efavirenz
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 721 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Study start
- 15 Oct 2014 (actual)
- Primary completion
- 5 Nov 2016 (actual)
- Study completion
- 7 Mar 2017 (actual)
- First posted
- 6 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID | Experimental | Drug: Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BIDMaraviroc (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 |
| Efavirenz QD + Zidovudine/Lamivudine BID | Active comparator | Drug: Efavirenz QD + Zidovudine/Lamivudine BIDEfavirenz (600 mg once daily) added to Zidovudine/Lamivudine (300 mg/150 mg twice daily |
| Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine BID | Experimental | Drug: Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QDMaraviroc (UK-427,857) 300 mg twice daily added to Zidovudine/Lamivudine (300 mg/150 mg twice daily) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BIDmaraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily | Drug | Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID |
| Efavirenz QD + Zidovudine/Lamivudine BIDefavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily) | Drug | Efavirenz QD + Zidovudine/Lamivudine BID |
| Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QDmaraviroc (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 BID |
Primary outcome
Change From Baseline in CD4/CD8 ratio
Time frame: From baseline to week 120
2 secondary outcomes
Change From Baseline in CD8+ T cells
Time frame: From baseline to week 120
Change From Baseline in CD4/CD8 ratio
Time frame: From baseline to week 120
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID, Efavirenz QD + Zidovudine/Lamivudine BID and Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QD in people with HIV/AIDS, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in CD4/CD8 ratio (time frame: From baseline to week 120). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.