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HIV InfectionsPhase 3ENCORE1NCT01011413

Safety and Efficacy of Reduced Versus Standard Dose Efavirenz (EFV) Plus Two Nucleotides in Antiretroviral-naïve Adults.

A Phase 3 study testing Efavirenz 600mg and Efavirenz 400mg in people with HIV Infections, run by Kirby Institute at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Clinical data suggests that the standard dose of the anti-HIV medication, efavirenz (EFV), could be reduced without compromising its effectiveness. Lower drug doses could have fewer side effects and would make EFV more affordable. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
HIV Infections
What is being tested?
Efavirenz 600mg and Efavirenz 400mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
636 participants
Where
1 siteAustralia
Study dates
Aug 2011to Aug 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • HIV-1 positive by licensed diagnostic test
  • aged >16 years of age (or minimum age as determined by local regulations or as legal requirements dictate)
  • 50 < cluster of differentiation (CD)4 <500 cells/µL
  • No prior AIDS-defining illness, using the Center for Diseases Control 1993 Case Definition (except pulmonary tuberculosis)
  • HIV RNA ≥1000 copies/mL
  • no prior exposure to antiretroviral therapy (ART) (including short course ART for preventing MTCT)
  • calculated creatinine clearance (CLCr) more than or equal to 50 mL/min (Cockcroft-Gault formula)
  • provision of written informed consent.

Who cannot join

  • the following laboratory values:
  • absolute neutrophil count (ANC) <500 cells/μL
  • hemoglobin <7.0 g/dL
  • platelet count <50,000 cells/μL
  • alanine aminotransferase and/or aspartate aminotransferase >5 x upper limit of normal
  • pregnant women or nursing mothers
Show all 10Show fewer
  • active opportunistic or malignant disease not under adequate control
  • use of immunomodulators within 30 days prior to screening
  • use of any prohibited medications
  • current alcohol or illicit substance use that might adversely affect study participation

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • St Vincent's Hospital

    Sydney, New South Wales, 2010

Other trials in Australia

About this study

Official title: A Randomised, Double-blind, Placebo-controlled, Trial to Compare the Safety and Efficacy of Reduced Dose Versus Standard Dose EFV Plus Two Nucleotides (N(t)RTI) in Antiretroviral-naïve HIV-infected Adults Over 96 Weeks

Clinical data suggests that the standard dose of the anti-HIV medication, efavirenz (EFV), could be reduced without compromising its effectiveness. Lower drug doses could have fewer side effects and would make EFV more affordable. The purpose of this study is to compare the safety and effectiveness, over 96 weeks, of standard (600mg) versus reduced dose (400mg) EFV in controlling HIV as part of initial combination antiretroviral therapy.

Read the detailed description

In this international, multicenter trial, 630 HIV infected patients who have not received any previous treatment for their HIV-infection will be enrolled. Participants will be randomized equally (1:1) to receive Truvada (tenofovir and emtricitabine) with either the standard or reduced dose of EFV. Neither the study doctor nor the participant will know which treatment the participant is receiving. Physical examinations, laboratory analyses and questionnaires will be performed at the 11 study visits at screening, baseline (Week 0), Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96. The primary aim of this study is to compare between treatment groups the proportion of patients with undetectable HIV viral load (HIV RNA < 200 copies/mL) after 48 weeks. Information on immune function, drug adherence, resistance to antiretrovirals, quality of life, mental state and HIV-related conditions will also be collected. Blood samples will be collected for future testing. Interim analyses will be performed when the first 125 participants in each treatment group reach week 24 and when all participants reach week 24. These interim analyses will provide an early check that the reduced dose of EFV suppresses HIV infection as effectively as the standard dose of EFV. A follow-up analysis will be performed when all participants reach week 96.

Conditions
HIV Infections
Being tested
Efavirenz 600mg, Efavirenz 400mg
Keywords
HIV, Antiretroviral Therapy (ART), Efavirenz (EFV), Dose reduction
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Efavirenz 600mgDrug

    Also called Matrix EFV 200mg tablets

    3 x EFV 200 milligram (mg) tablets once daily

  • Efavirenz 400mgDrug

    Also called Matrix EFV 200mg tablets, Matrix EFV 200mg matched placebo tablets.

    2 x EFV 200 milligram (mg) tablets plus 1x matched EFV placebo tablet once daily

Study groups in NCT01011413
Study groupRoleWhat they receive
600 milligram (mg) EfavirenzActive comparatorEligible patients will be centrally randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)
Receives: Drug: Efavirenz 600mg
400mg EfavirenzExperimentalEligible patients will be centrally randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd).
Receives: Drug: Efavirenz 400mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Plasma HIV-1 RNA <200 Copies/mL 48 Weeks After Randomisation

    Percentage of participants in each of the treatment arms with centrally quantified plasma HIV-1 RNA viral load <200 copies/mL 48 weeks after randomisation.

    Measured: 48 weeks

Secondary outcomes (9)

  1. Percentage of Participants With Plasma HIV-1 RNA <400 Copies/mL and <50 Copies/mL at 48 and 96 Weeks After Randomisation

    Percentage of participants in each of the two treatment arms with plasma HIV-1 RNA <400 copies/mL and <50 copies/mL at 48 and 96 weeks after randomisation

    Measured: Baseline and 2 years

  2. Mean Change From Baseline in CD4+ T-cell Count

    Mean change from baseline to week 96 in CD4+ T-cell count/mm3 between the two treatment arms

    Measured: Baseline and 2 years

  3. Clinical Endpoints: Opportunistic Disease or Death, and Serious Non-AIDS-defining Events and Non-AIDS-related Mortality

    Number of participants in each randomised arm diagnosed with a serious non-AIDS defining event, who die from an AIDS-defining event, who die from a non-AIDS-defining event

    Measured: up to 2 years

  4. Change From Baseline in Metabolic Endpoints

    Change from baseline to week 96 in fasted total cholesterol, high density cholesterol and low density cholesterol, and glucose between randomised treatment arms

    Measured: Baseline and 2 years

  5. Adherence: Median Scores of Self-reported Adherence to Randomised Study Medications

    AIDS Clinical Trials Group (ACTG) 7-day adherence questionnaire scores. Maximum value is all pills taken every day; minimum value is no pills taken per day. Higher scores indicate a better outcome.

    Measured: 2 years

  6. Change From Baseline in Fasted Insulin Levels

    Change from baseline to week 96 in fasted insulin levels

    Measured: Baseline and 2 years

  7. Change in Selected Serum Biochemical Parameters

    Change from baseline to week 96 in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels between randomised treatment arms

    Measured: Baseline and 2 years

  8. Change From Baseline in Estimate Creatinine Clearance

    Change from baseline to week 96 in estimate creatinine clearance between randomised treatment arms

    Measured: Baseline and 2 years

  9. Steady-state Efavirenz Concentrations

    Steady-state efavirenz mid-dosing interval plasma concentrations

    Measured: Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2009 (estimated)
  2. Study startAug 2011
  3. Primary completionJun 2013
  4. Study completionAug 2014

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
636 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01011413
Sponsor's protocol ID
NCHECR-ENCORE1
Acronym
ENCORE1
Status last verified
Feb 2020
First submitted
9 Nov 2009
Last updated
21 Feb 2020
Data monitoring committee
Yes

Publications

  • ENCORE1 Study Group. Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial. Lancet. 2014 Apr 26;383(9927):1474-1482. doi: 10.1016/S0140-6736(13)62187-X. Epub 2014 Feb 10.

    PubMed 24522178

  • ENCORE1 Study Group; Carey D, Puls R, Amin J, Losso M, Phanupak P, Foulkes S, Mohapi L, Crabtree-Ramirez B, Jessen H, Kumar S, Winston A, Lee MP, Belloso W, Cooper DA, Emery S. Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study. Lancet Infect Dis. 2015 Jul;15(7):793-802. doi: 10.1016/S1473-3099(15)70060-5. Epub 2015 Apr 12.

    PubMed 25877963

  • Winston A, Amin J, Clarke A, Else L, Amara A, Owen A, Barber T, Jessen H, Avihingsanon A, Chetchotisakd P, Khoo S, Cooper DA, Emery S, Puls R; ENCORE Cerebrospinal Fluid (CSF) Substudy Team; ENCORE Cerebrospinal Fluid CSF Substudy Team. Cerebrospinal fluid exposure of efavirenz and its major metabolites when dosed at 400 mg and 600 mg once daily: a randomized controlled trial. Clin Infect Dis. 2015 Apr 1;60(7):1026-32. doi: 10.1093/cid/ciu976. Epub 2014 Dec 11.

    PubMed 25501988

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Efavirenz 600mg and Efavirenz 400mg in people with HIV Infections, run by Kirby Institute at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. 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 21 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

Yes. Results are posted in the registry (first posted 21 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Plasma HIV-1 RNA <200 Copies/mL 48 Weeks After Randomisation (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01011413, which also lists 3 linked publications.

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 21 Feb 2020.

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