Human Immunodeficiency Virus (HIV)Phase 4HANDralNCT01448486

A Study of the Neurological Effects of Adding Raltegravir to HAART Regimen in Patients With HIV

A Phase 4 study testing Raltegravir in people with Human Immunodeficiency Virus (HIV) and HIV Associated Neurocognitive Disorders (HAND), run by St Vincent's Hospital, Sydney at 2 sites in Australia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Human Immunodeficiency Virus (HIV), HIV Associated Neurocognitive Disorders (HAND)
What is being tested?: Raltegravir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 6 participants
Where: 2 sitesAustralia
Study dates: Oct 2011to Oct 2013
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

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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)

Trial locations and contacts

2 sites in 1 country.

Australia2 sites

The Alfred Hospital
Melbourne, Victoria, 3181
St. Vincent's Hospital
Sydney, New South Wales, 2010

Other trials in Australia

About this study

Official title: A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment

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.

Conditions: Human Immunodeficiency Virus (HIV), HIV Associated Neurocognitive Disorders (HAND)
Being tested: Raltegravir
Keywords: HIV, HAND, Human Immunodeficiency Virus, Raltegravir, HIV Associated Neurocognitive Disorders, Neuro-HAART, Neurocognitive, Neurology
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RaltegravirDrug
Also called Isentress
Oral raltegravir, 400 mg tablet, twice daily for one year.

Study groups in NCT01448486
Study group	Role	What they receive
Standard of Care HAART	No intervention	Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART).
Raltegravir	Experimental	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). Receives: Drug: Raltegravir

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, 6 months and 12 months

Secondary outcomes (1)

Cerebrospinal Fluid
To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir.
Measured: Baseline and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2011Oct 2013

First posted7 Oct 2011 (estimated)
Study startOct 2011
Primary completionOct 2013
Study completionOct 2013

Why it stopped: Funding withdrawn based on unacceptably slow recruitment rate.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Human Immunodeficiency Virus (HIV)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01448486
Sponsor's protocol ID: 11/033
Other IDs: IISP 37693
Acronym: HANDral
Status last verified: May 2016
First submitted: 5 Oct 2011
Last updated: 27 Jun 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment
ClinicalTrials.gov ID: NCT01448486
Acronym / sponsor ID: HANDral / 11/033
Conditions: Human Immunodeficiency Virus (HIV), HIV Associated Neurocognitive Disorders (HAND)
Keywords: HIV, HAND, Human Immunodeficiency Virus, Raltegravir, HIV Associated Neurocognitive Disorders, Neuro-HAART, Neurocognitive, Neurology
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Funding withdrawn based on unacceptably slow recruitment rate.
Enrolment: 6 participants (actual)
Lead sponsor: St Vincent's Hospital, SydneyUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: Oct 2011
Primary completion: Oct 2013 (actual)
Study completion: Oct 2013 (actual)
First posted: 7 Oct 2011 (estimated)
Results: Posted 3 Jan 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Standard of Care HAART	No intervention	–Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART).
Raltegravir	Experimental	Drug: RaltegravirParticipants 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).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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)

Key exclusion criteria (10 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RaltegravirAlso: IsentressOral raltegravir, 400 mg tablet, twice daily for one year.	Drug	Raltegravir

Primary outcome

Neurocognitive Function
Time frame: Baseline, 6 months and 12 months
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.

1 secondary outcome

Cerebrospinal Fluid
Time frame: Baseline and 12 months

Results and safety

Results posted to the registry on 3 Jan 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Raltegravir	3	3
Standard of Care HAART	3	3

Primary outcome: Neurocognitive Function

Time frame: Baseline, 6 months and 12 months. Mean (Standard Error). Unit: Global Neurocognitive Z-Score

Measure	Raltegravir n = 3	Standard of Care HAART n = 3
Baseline	-0.83 (0.29)	-0.39 (0.20)
6 months	-0.55 (0.12)	-0.48 (0.45)
12 months	-0.47 (0.46)	-0.54 (0.32)

Population analysed: Study was terminated prematurely with an incomplete study dataset any before any meaningful statistical analysis of the data (including change over the study time-points) could be performed.

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Raltegravir	0 of 3 (0%)	1 of 3 (33.3%)	Not reported
Standard of Care HAART	0 of 3 (0%)	1 of 3 (33.3%)	Not reported

Limitations and caveats (from the sponsor): Early termination leading to incomplete dataset with sample size too small to produce any meaningful statistical analysis.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bruce J Brew, MBBS, PhD principal investigator

St Vincent's Hospital, Sydney

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Raltegravir in people with Human Immunodeficiency Virus (HIV) and HIV Associated Neurocognitive Disorders (HAND), run by St Vincent's Hospital, Sydney at 2 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Neurocognitive Function (time frame: Baseline, 6 months and 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01448486.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2016.