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Trial registered on ANZCTR


Registration number
ACTRN12612001194853
Ethics application status
Approved
Date submitted
21/02/2012
Date registered
13/11/2012
Date last updated
13/11/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Efavirenz (EFV) central nervous system exposure sub-study
Scientific title
The CNS sub-study of a randomised, double-blind, placebo-controlled, clinical trial to compare the safety and efficacy of reduced dose efavirenz (EFV) with standard dose EFV plus 2N(t)RTI in antiretroviral-naive HIV-infected individuals over 96 weeks
Secondary ID [1] 279994 0
NCT01451333 ClinicalTrials.gov
Universal Trial Number (UTN)
Trial acronym
The CNS sub-study for Encore1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV 285902 0
Condition category
Condition code
Infection 286094 286094 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Tenofovir (TDF) (300mg qd (once daily))/emtricitabine (FTC) (200mg qd) + efavirenz(EFV )(600mg qd; 3 x 200mg qd) all oral tablets
Intervention code [1] 284320 0
Treatment: Drugs
Comparator / control treatment
Tenofovir (TDF) (300mg qd(once daily)/emtricitabine(FTC) (200mg qd) + efavirenz(EFV )(400mg qd; 2 x 200mg + 1 x placebo qd) all oral tablets

Placebo - identical taste and appearance without the active ingredients.
Control group
Placebo

Outcomes
Primary outcome [1] 286569 0
The primary endpoint is to describe the CSF exposure of EFV when dosed at 400mg and 600mg daily.

CSF exposure will be assessed from CSF fluid and blood plasma from a special pharmacokinetic laboratory at Liverpook UK.
Timepoint [1] 286569 0
48 weeks
Secondary outcome [1] 296188 0
The relationship between CSF EFV exposure and plasma exposure (CSF:plasma ratio)


CSF exposure will be assessed from CSF fluid and blood plasma from a special pharmacokinetic laboratory at Liverpook UK.
Timepoint [1] 296188 0
48 weeks
Secondary outcome [2] 296189 0
The relationship between CSF EFV exposure and neuropsychiatric side effects (as assessed in main study protocol)


CSF exposure and neuropsychiatric side effects will be assessed from the main study data compared to CSF fuild and blood plasma exposure
Timepoint [2] 296189 0
48 weeks
Secondary outcome [3] 296190 0
CSF HIV RNA measurement after 12 to 24 weeks of study therapy


CSF HIV RNA measurement will be assessed from CSF fluid and blood plasma using ultrasensitive RNA assay at imperial college, UK
Timepoint [3] 296190 0
48 weeks

Eligibility
Key inclusion criteria
All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Existing neurological disease which in the opinion of the
investigator would be a contra-indication to lumbar
puncture examination

CNS opportunistic infections in the past 12 weeks

Bacterial or viral meningitis in the past 12 weeks

Head injury requiring medical assessment in the past 12 weeks

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)
Central randomisation by computer on participants in the Main study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
simple randomisation using a randomisation table created by computer software (ie computerised sequence generation)
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
Completed
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 outside Australia
Country [1] 4156 0
Germany
State/province [1] 4156 0
Country [2] 4157 0
Thailand
State/province [2] 4157 0
Country [3] 4158 0
United Kingdom
State/province [3] 4158 0
London

Funding & Sponsors
Funding source category [1] 284752 0
Self funded/Unfunded
Name [1] 284752 0
Address [1] 284752 0
Country [1] 284752 0
Primary sponsor type
University
Name
Kirby Institute, University of New South Wales
Address
University of New South Wales
Anzac parade, Kensington
NSW 2052
Country
Australia
Secondary sponsor category [1] 283644 0
None
Name [1] 283644 0
Address [1] 283644 0
Country [1] 283644 0
Other collaborator category [1] 260560 0
University
Name [1] 260560 0
Imperial college london
Address [1] 260560 0
Imperial College London
St. Mary's Campus
Winston Churchill Wing
Clinical Trials Centre
Praed Street
London W2 1NY
Country [1] 260560 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286753 0
NRES Committee North West - Greater Manchester West
Ethics committee address [1] 286753 0
NRES Committee London - Fulham
HRA NRES Centre North West
Barlow House 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ
Ethics committee country [1] 286753 0
United Kingdom
Date submitted for ethics approval [1] 286753 0
Approval date [1] 286753 0
14/02/2011
Ethics approval number [1] 286753 0
10/H0711/53

Summary
Brief summary
Persistent HIV replication in the central nervous system (CNS) compartment may put subjects at risk of developing HIV-related brain disease. Important factors associated with the development of HIV-related brain disease include sub-therapeutic concentrations of antiretroviral drugs in the CNS.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33812 0
Address 33812 0
Country 33812 0
Phone 33812 0
Fax 33812 0
Email 33812 0
Contact person for public queries
Name 17059 0
Carlo Dazo
Address 17059 0
University of New South Wales
Anzac parade, Kensington
NSW
2052
Country 17059 0
Australia
Phone 17059 0
+61293850900
Fax 17059 0
Email 17059 0
encore@kirby.unsw.edu.au
Contact person for scientific queries
Name 7987 0
Dr. Rebekah Puls
Address 7987 0
University of New South Wales
Anzac parade, Kensington
NSW
2052
Country 7987 0
Australia
Phone 7987 0
+61293850900
Fax 7987 0
Email 7987 0
encore@kirby.unsw.edu.au

No data has been provided for results reporting
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