The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01448486




Registration number
NCT01448486
Ethics application status
Date submitted
5/10/2011
Date registered
7/10/2011
Date last updated
27/06/2016

Titles & IDs
Public title
A Study of the Neurological Effects of Adding Raltegravir to HAART Regimen in Patients With HIV
Scientific title
A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment
Secondary ID [1] 0 0
IISP 37693
Secondary ID [2] 0 0
11/033
Universal Trial Number (UTN)
Trial acronym
HANDral
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Human Immunodeficiency Virus (HIV) 0 0
HIV Associated Neurocognitive Disorders (HAND) 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)
Neurological 0 0 0 0
Other neurological disorders
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Raltegravir

No Intervention: Standard of Care HAART - Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART).

Experimental: Raltegravir - Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART) with the addition of Raltegravir 400 mg twice daily (BID).


Treatment: Drugs: Raltegravir
Oral raltegravir, 400 mg tablet, twice daily for one year.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Neurocognitive Function - Change in overall neurocognitive performance, defined as a global neurocognitive z-score, over the study time-period (baseline, 6-months, 12-months). To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, SD=1) and 2) the set of individual subtest z-scores were averaged to generate a single composite (global) z-score for each subject. Lower (negative) scores therefore indicate greater levels of cognitive impairment.
Timepoint [1] 0 0
Baseline, 6 months and 12 months
Secondary outcome [1] 0 0
Cerebrospinal Fluid - To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir.
Timepoint [1] 0 0
Baseline and 12 months

Eligibility
Key inclusion criteria
- HIV positive

- On HAART, with plasma HIV viral load < 50 copies/ml for previous 12 months or more

- Able to provide informed consent

- HAND diagnosis, with symptom progression within previous 6 months (while on existing
HAART regimen)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Non-HIV related neurological disorders and active CNS opportunistic infection (as
assessed by full blood count, electrolytes, creatinine, glucose, LFT's, cryptococcal
antigen, VDRL, MRI brain scan and CSF fluid analysis for cell count, protein, glucose,
culture, VDRL and cryptococcal antigen)

- Psychiatric disorders on the psychotic axis

- Current major depression

- Current substance use disorder, or severe substance use disorders within 12 months of
study entry

- Active HCV (detectable HCV RNA)

- History of loss of consciousness > 1 hour

- Non-proficient in English

- Medications known to pharmacologically interact with ARV's

- Currently taking an Integrase Inhibitor

- Pregnancy (as assessed by the urine pregnancy test)

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
NSW,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Sydney
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
3181 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
St Vincent's Hospital, Sydney
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme Corp.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
HIV related cognitive impairment still occurs despite highly active antiretroviral therapy
(HAART). HIV disease affects the brain in 20-40% of patients with advancing HIV disease
leading to varying degrees of cognitive impairment, recently termed HIV associated
neurocognitive disorders (HAND).

HAND may occur in patients who are virally suppressed in both blood and CSF. Patients with
HIV Associated Neurological Disorders (HAND) who are virally suppressed in both their blood
and cerebrospinal fluid (CSF), whilst on a highly active antiretroviral therapy (HAART)
regimen may have significant cognitive improvement with HAART intensification with the
medication Raltegravir; compared to those who remain on their existing regimen.

This study will be a prospective, interventional, randomised and unblinded controlled
clinical trial. The aim of this study will be to determine whether HAART intensification with
the medication Raltegravir, leads to significant improvement in HIV associated neurological
disorders (HAND).

Patients with the recent progression (within 6 months) of HAND (validated by
neuropsychological assessment) on HAART who are virally suppressed (<50 copies per ml) in
blood and CSF will be randomised to have their existing HAART regimen intensified with
raltegravir 400mg twice daily, or not. The control arm will remain on their medication
regimen as prescribed. The target is to enrol 110 patients into the control group, and 110
patients into the Raltegravir intensification group.

Patients will undergo baseline neuropsychological testing, MRI, blood tests, and cerebral
spinal fluid (CSF) tests (via a lumbar puncture). The methods used to determine the
effectiveness of adding Raltegravir, will include further neuropsychological testing at 6
months; and neuropsychological testing, MRI and CSF assessment at 12 months.
Neuropsychological testing completed at 6 and 12 months will be completed by a "blind
assessor", in that they will have no knowledge of which arm (treatment or control) the
participant is enrolled in.

An evaluation (neuropsychological testing) will be performed should the patient deteriorate
during the course of the study, as recognised by the patient's managing physician. The
decision of the Antiretroviral medication regimen to be used in such a case will be
determined by the managing physician. At the end of the study protocol (12 months) the
patient's HAART therapy will be managed by their primary physician.
Trial website
https://clinicaltrials.gov/show/NCT01448486
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bruce J Brew, MBBS, PhD
Address 0 0
St Vincent's Hospital, Sydney
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/show/NCT01448486