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Trial registered on ANZCTR


Registration number
ACTRN12610001097033
Ethics application status
Approved
Date submitted
4/02/2010
Date registered
15/12/2010
Date last updated
6/07/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised, double-blind, placebo-controlled, clinical trial to compare the safety and efficacy of reduced dose efavirenz (EFV) with standard dose EFV plus two nucleotide reverse transcriptase inhibitors (N(t)RTI) in antiretroviral-naïve Human Immunodeficiency virus (HIV)-infected individuals over 96 weeks.
Scientific title
A randomised, double-blind, placebo-controlled, clinical trial to compare the safety and efficacy of reduced dose efavirenz (EFV) with standard dose EFV plus two nucleotide reverse transcriptase inhibitors (N(t)RTI) in antiretroviral-naïve Human Immunodeficiency virus (HIV)-infected individuals over 96 weeks.
Secondary ID [1] 253295 0
Encore1
Universal Trial Number (UTN)
Trial acronym
Encore1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV infection 252037 0
Condition category
Condition code
Infection 252227 252227 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
400mg Efavirenz plus 300 mg tenofovir and 200mg emtricitabine for 1 year once daily for each oral tablets
Intervention code [1] 241434 0
Treatment: Drugs
Comparator / control treatment
600mg Efavirenz plus 300 mg tenofovir and 200mg emtricitabine for 1 year once daily oral tablets
Control group
Dose comparison

Outcomes
Primary outcome [1] 253099 0
To compare between treatment groups the proportions of patients with HIV Ribonucleic acid (RNA) <200 copies/mL 96 weeks after randomisation by blood assay
Timepoint [1] 253099 0
2 years after randomisation
Secondary outcome [1] 257964 0
Proportion of patients at 48 weeks with plasma HIV RNA <400 copies/mL and <50 copies/mL through blood assay
Timepoint [1] 257964 0
2 years after randomisation
Secondary outcome [2] 268638 0
Change from baseline in white blood T cell count/microlitre by blood assay.
Timepoint [2] 268638 0
2 years after randomisation
Secondary outcome [3] 268639 0
Rate of opportunistic disease or death by statistical analysis
Timepoint [3] 268639 0
2 years after randomisation
Secondary outcome [4] 268640 0
Cahnge from baseline in fasted lipids (cholesterol, good and bad fats) by fasting blood analysis.
Timepoint [4] 268640 0
2 years after randomisation
Secondary outcome [5] 268641 0
Change from baseline in selected body biochemicals such as sodium, potassium, calcium etc.
Timepoint [5] 268641 0
2 years after randomisation
Secondary outcome [6] 268642 0
self reported adherence to randomised study medications by questionnaires
Timepoint [6] 268642 0
2 years after randomisation
Secondary outcome [7] 268643 0
Change from baseline health status scores by questionnaires
Timepoint [7] 268643 0
2 years after randomisation
Secondary outcome [8] 268644 0
Patterns of genotypic viral resistance from medications
Timepoint [8] 268644 0
2 years after randomisation
Secondary outcome [9] 268645 0
Steady state efavirenz concentrations measured by plasma and dried blood spot sample analysis
Timepoint [9] 268645 0
2 years after randomisation
Secondary outcome [10] 268646 0
Relationship between dried blood spot and plasma samples when measuring viral load and efavirenz concentrations
Timepoint [10] 268646 0
2 years after randomisation

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 < CD4 <350 cells/microlitres or previous aquired immune deficiency syndrome-defining illness
*HIV RNA greater than or equal to 1000 copies/mL
*no prior exposure to antiretrovirals (including short course antiretrovirals for preventing mother to child transmission)
*calculated creatinine clearance (CLCr) must be greater than or equal to 50 mL/min (Cockcroft-Gault formula)
*provision of written informed consent.
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*the following laboratory values:
*absolute neutrophil count (ANC) <500 cells/microlitre
*hemoglobin <7.0 g/dL
*platelet count <50,000 cells/microlitre
*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)
If the participant agreed to participate in the study they will be randomised to receive truvada with either the standard or reduced dose of efavirenz. Which of the two regimens they will receive will be chosen at random by a computer and the doctor has no influence on the treatment chosen for them. Participants will have an equal (1:1) chance of receiving either regimen. This is a double-blind study so neither participant nor the doctor will be aware of which treatment participants are receiving.

Participants will be told which treatment they were given as soon as the final study results are released.

participants are required to attend the clinic on 11 occasions and have one telephone interview over the 96 weeks of the study.

allocation will be done by the study statisticial who will program this to the computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Which of the two regimens participants will receive will be chosen at random by a computer. It will generate a three letter code (usually first letter of the first name and two letters of the last name) and a 5 randomisation number.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 2273 0
Argentina
State/province [1] 2273 0
Country [2] 2274 0
Chile
State/province [2] 2274 0
Country [3] 2275 0
China
State/province [3] 2275 0
Country [4] 2276 0
Germany
State/province [4] 2276 0
Country [5] 2277 0
Hong Kong
State/province [5] 2277 0
Country [6] 2278 0
India
State/province [6] 2278 0
Country [7] 2279 0
Israel
State/province [7] 2279 0
Country [8] 2280 0
Malaysia
State/province [8] 2280 0
Country [9] 2281 0
Mexico
State/province [9] 2281 0
Country [10] 2282 0
Nigeria
State/province [10] 2282 0
Country [11] 2283 0
Singapore
State/province [11] 2283 0
Country [12] 2284 0
South Africa
State/province [12] 2284 0
Country [13] 2285 0
Taiwan, Province Of China
State/province [13] 2285 0
Country [14] 2286 0
Thailand
State/province [14] 2286 0
Country [15] 2287 0
United Kingdom
State/province [15] 2287 0

Funding & Sponsors
Funding source category [1] 256467 0
University
Name [1] 256467 0
University of New South Wales
Address [1] 256467 0
UNSW Sydney NSW 2052
Country [1] 256467 0
Australia
Primary sponsor type
Government body
Name
National Centre for HIV Epidemiology and Clinical Research
Address
45 beach street, Coogee. New South Wales 2034
Country
Australia
Secondary sponsor category [1] 255777 0
None
Name [1] 255777 0
Address [1] 255777 0
Country [1] 255777 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258520 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 258520 0
Level 6, de Lacy Building
St Vincents Hospital
390 Victoria Street,
Darlinghurst NSW 2010
Ethics committee country [1] 258520 0
Australia
Date submitted for ethics approval [1] 258520 0
01/03/2010
Approval date [1] 258520 0
05/05/2010
Ethics approval number [1] 258520 0
10/056

Summary
Brief summary
The recommended dosage for some drugs currently used to treat HIV infection is highly effective but clinical data suggests that the doses could be reduced without compromising their effectiveness. Lower drug doses could have fewer side effects and could be tolerated better, making it easier for people to take and stay on their anti-HIV medication. Dose reduction would also make the drugs cheaper; this would allow more people to be treated and free up money for other important work in the fight against HIV such as education and prevention programs.

Two different regimens containing either the standard dose or a reduced dose of efavirenz will be compared:
I. efavirenz 600mg + truvada (tenofovir and emtricitabine)
II. efavirenz 400mg + truvada (tenofovir and emtricitabine)

Tenofovir, emtricitabine and efavirenz are all licensed as individual drugs for the treatment of HIV disease in many countries around the world. Efavirenz is only licensed at the standard dose of 600mg. Emtricitabine and tenofovir are provided as a fixed dose combination that is not currently licensed in every country involved in this study. A fixed dose combination means that the two drugs are incorporated into one pill.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30403 0
Address 30403 0
Country 30403 0
Phone 30403 0
Fax 30403 0
Email 30403 0
Contact person for public queries
Name 13650 0
Dr. Rebekah Puls
Address 13650 0
45 Beach Street, Coogee, New South Wales, Australia, 2034
Country 13650 0
Australia
Phone 13650 0
+612 9385 0900
Fax 13650 0
+612 9385 0910
Email 13650 0
rpuls@nchecr.unsw.edu.au
Contact person for scientific queries
Name 4578 0
Dr. Mark Boyd
Address 4578 0
45 Beach Street, Coogee, New South Wales, Australia, 2034
Country 4578 0
Australia
Phone 4578 0
+612 9385 0900
Fax 4578 0
+612 9385 0910
Email 4578 0
mboyd@nchecr.unsw.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary