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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01011413




Registration number
NCT01011413
Ethics application status
Date submitted
9/11/2009
Date registered
11/11/2009
Date last updated
21/02/2020

Titles & IDs
Public title
Safety and Efficacy of Reduced Versus Standard Dose Efavirenz (EFV) Plus Two Nucleotides in Antiretroviral-naïve Adults.
Scientific 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
Secondary ID [1] 0 0
NCHECR-ENCORE1
Universal Trial Number (UTN)
Trial acronym
ENCORE1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Efavirenz 600mg
Treatment: Drugs - Efavirenz 400mg

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

Experimental: 400mg Efavirenz - 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).


Treatment: Drugs: Efavirenz 600mg
3 x EFV 200 milligram (mg) tablets once daily

Treatment: Drugs: Efavirenz 400mg
2 x EFV 200 milligram (mg) tablets plus 1x matched EFV placebo tablet once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Plasma HIV-1 RNA <200 Copies/mL 48 Weeks After Randomisation
Timepoint [1] 0 0
48 weeks
Secondary outcome [1] 0 0
Percentage of Participants With Plasma HIV-1 RNA <400 Copies/mL and <50 Copies/mL at 48 and 96 Weeks After Randomisation
Timepoint [1] 0 0
Baseline and 2 years
Secondary outcome [2] 0 0
Mean Change From Baseline in CD4+ T-cell Count
Timepoint [2] 0 0
Baseline and 2 years
Secondary outcome [3] 0 0
Clinical Endpoints: Opportunistic Disease or Death, and Serious Non-AIDS-defining Events and Non-AIDS-related Mortality
Timepoint [3] 0 0
up to 2 years
Secondary outcome [4] 0 0
Change From Baseline in Metabolic Endpoints
Timepoint [4] 0 0
Baseline and 2 years
Secondary outcome [5] 0 0
Adherence: Median Scores of Self-reported Adherence to Randomised Study Medications
Timepoint [5] 0 0
2 years
Secondary outcome [6] 0 0
Change From Baseline in Fasted Insulin Levels
Timepoint [6] 0 0
Baseline and 2 years
Secondary outcome [7] 0 0
Change in Selected Serum Biochemical Parameters
Timepoint [7] 0 0
Baseline and 2 years
Secondary outcome [8] 0 0
Change From Baseline in Estimate Creatinine Clearance
Timepoint [8] 0 0
Baseline and 2 years
Secondary outcome [9] 0 0
Steady-state Efavirenz Concentrations
Timepoint [9] 0 0
Week 4

Eligibility
Key inclusion criteria
* 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.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2014
Sample size
Target
Accrual to date
Final
636
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincent's Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Sydney

Funding & Sponsors
Primary sponsor type
Government body
Name
Kirby Institute
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT01011413
Trial related presentations / 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. Erratum In: Lancet. 2014 Apr 26;383(9927):1464.
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. Erratum In: Lancet Infect Dis. 2015 Jul;15(7):761. doi: 10.1016/S1473-3099(15)00090-0.
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. Erratum In: Clin Infect Dis. 2015 Jul 1;61(1):143. doi: 10.1093/cid/civ348. Avinghsanon, Anchalee [corrected to Avihingsanon, Anchalee].
Public notes

Contacts
Principal investigator
Name 0 0
David Cooper, Professor
Address 0 0
Kirby Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01011413