NCT01011413

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
636

participants targeted

Target at P50-P75 for phase_3 hiv-infections

Timeline
Completed

Started Aug 2011

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 9, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 11, 2009

Completed
1.7 years until next milestone

Study Start

First participant enrolled

August 1, 2011

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2013

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2014

Completed
5.6 years until next milestone

Results Posted

Study results publicly available

February 21, 2020

Completed
Last Updated

February 21, 2020

Status Verified

February 1, 2020

Enrollment Period

1.8 years

First QC Date

November 9, 2009

Results QC Date

February 22, 2018

Last Update Submit

February 18, 2020

Conditions

HIV Infections

Keywords

HIVAntiretroviral Therapy (ART)Efavirenz (EFV)Dose reduction

Outcome Measures

Primary Outcomes (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.

    48 weeks

Secondary Outcomes (9)

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

    Baseline and 2 years

  • Mean Change From Baseline in CD4+ T-cell Count

    Baseline and 2 years

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

    up to 2 years

  • Change From Baseline in Metabolic Endpoints

    Baseline and 2 years

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

    2 years

  • +4 more secondary outcomes

Study Arms (2)

600 milligram (mg) Efavirenz

ACTIVE COMPARATOR

Eligible patients will be centrally randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)

Drug: Efavirenz 600mg

400mg Efavirenz

EXPERIMENTAL

Eligible patients will be centrally randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd).

Drug: Efavirenz 400mg

Interventions

Efavirenz 600mgDRUG

3 x EFV 200 milligram (mg) tablets once daily

Also known as: Matrix EFV 200mg tablets
600 milligram (mg) Efavirenz
Efavirenz 400mgDRUG

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

Also known as: Matrix EFV 200mg tablets, Matrix EFV 200mg matched placebo tablets.
400mg Efavirenz

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • \< 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.

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Related Publications (3)

  • 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.

    PMID: 24522178RESULT

  • 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.

    PMID: 25877963RESULT

  • 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.

    PMID: 25501988DERIVED

Related Links

MeSH Terms

Conditions

HIV Infections

Interventions

efavirenz

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Results Point of Contact

Title
Sean Emery
Organization
University of New South Wales
semery@kirby.unsw.edu.au
02 9385 0900

Study Officials

  • David Cooper, Professor

    Kirby Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 9, 2009

First Posted

November 11, 2009

Study Start

August 1, 2011

Primary Completion

June 1, 2013

Study Completion

August 1, 2014

Last Updated

February 21, 2020

Results First Posted

February 21, 2020

Record last verified: 2020-02

Locations

AU(1)