HIV InfectionPhase 4NCT00843713
Effect of Raltegravir on Endothelial Function in HIV-Infected Patients
A Phase 4 study testing raltegravir in people with HIV Infection and Inflammation, run by University of California, San Francisco at 1 site in United States.
Trial summary
Recent studies suggest that HIV patients are at increased risk for cardiovascular events; however, the mechanisms underlying this increased risk remain unclear. Our group was one of the first to demonstrate that HIV infection is independently associated with accelerated atherosclerosis, as measured by carotid… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection, Inflammation, Cardiovascular Disease
- What is being tested?
- raltegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Feb 2014
- 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
- Stable antiretroviral therapy for at least 12 months
- All plasma HIV RNA levels within the past year must be below level of detection (< 50 copies RNA/mL), although isolated single values > 50 but < 200 copies will be allowed.
- Screening plasma HIV RNA levels < 50 copies RNA/mL
- >90% adherence to therapy within the preceding 30 days, as determined by self-report
- Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
- CD4<350 cells/mm3 for at least one year ("immunologic non-responder") or CD4>=350 cells/mm3 for at least one year ("immunologic responder").
Who cannot join
- Ongoing or prior use of any integrase inhibitor or R5 inhibitor.
- Patients who plan to modify existing antiretroviral therapy in the next 24 weeks for any reason
- Serious illness requiring hospitalization or parental antibiotics within preceding 3 months
- Concurrent or recent exposure to any immunomodulatory drugs
- Advanced liver disease or active hepatitis B or C
- Patients with systolic blood pressure <100/70
- Starting or stopping statin therapy during the trial
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94110
About this study
Official title: A Randomized, Controlled Trial Assessing the Effects of Raltegravir Intensification on Endothelial Function in Treated HIV Infection
Recent studies suggest that HIV patients are at increased risk for cardiovascular events; however, the mechanisms underlying this increased risk remain unclear. Our group was one of the first to demonstrate that HIV infection is independently associated with accelerated atherosclerosis, as measured by carotid artery-intima media thickness (IMT), and that HIV-associated inflammation may be driving this accelerated atherosclerosis. The mechanism by which HIV disease independent of any drug-specific toxicity increases the risk of cardiovascular disease during HAART is not known. We hypothesize that even well controlled HIV infection is independently associated with cardiovascular risk and that further decreasing HIV-associated inflammation adding newer antiretroviral agents will also decrease cardiovascular risk.
We will perform a small clinical trial of approximately 50 HIV-infected patients each to study the relationship between HIV infection, inflammation, thrombosis, atherogenic lipoproteins, and measures of atherosclerosis. We propose the following specific aims: Aim 1: To determine the influence of traditional and novel markers of inflammation on endothelial function and IMT progression; Aim 2: To determine if "intensification" with raltegravir in subjects on long-term antiretroviral therapy with clinically undetectable HIV RNA levels will improve endothelial function, and to determine if this effect is mediated by alterations in inflammatory markers, lipoproteins and/or thrombotic factors. For Aim 2, subjects from 2 randomized, double-blind, placebo-controlled raltegravir intensification studies will be asked to co-enroll in this cardiovascular study.
- Conditions
- HIV Infection, Inflammation, Cardiovascular Disease, HIV Infections
- Being tested
- raltegravir, Placebo
- Keywords
- HIV, endothelium, inflammation, Treatment Experienced
- Medical subject headings
- HIV Infections, Inflammation, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
raltegravirDrug
For patients assigned to the raltegravir group, subjects will receive raltegravir 400mg to be taken by mouth twice daily for 24 weeks in addition to taking their current HIV medication
PlaceboDrug
For the patient assigned to the placebo group, subjects will take a matching placebo pill 400mg to be taken by mouth twice daily for 24 weeks in addition to taking their current HIV medication
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | For subjects assigned to the placebo group, patients will take a matching placebo pill of 400 mg by mouth twice daily for 24 weeks in addition to taking their current HIV medication Receives: Drug: Placebo |
| Raltegravir | Active comparator | For subjects assigned to the active comparator group, they will receive raltegravir at 400 mg by mouth twice daily for 24 weeks in addition to continuing to take their current HIV medication Receives: Drug: raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD)
Measurements in the change of brachial artery diameter from pre and post treatment.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2009 (estimated)
- Study startJan 2009
- Primary completionNov 2013
- Study completionFeb 2014
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Priscilla Hsue, University of California, San Francisco
- Investigators
- Priscilla Hsue, MD, Principal investigator, San Francisco General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00843713
- Sponsor's protocol ID
- 1R01HL095130-01
- Status last verified
- Dec 2018
- First submitted
- 12 Feb 2009
- Last updated
- 12 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hatano H, Scherzer R, Wu Y, Harvill K, Maka K, Hoh R, Sinclair E, Palmer S, Martin JN, Busch MP, Deeks SG, Hsue PY. A randomized controlled trial assessing the effects of raltegravir intensification on endothelial function in treated HIV infection. J Acquir Immune Defic Syndr. 2012 Nov 1;61(3):317-25. doi: 10.1097/QAI.0b013e31826e7d0f.
PubMed 22918156
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled Trial Assessing the Effects of Raltegravir Intensification on Endothelial Function in Treated HIV Infection
- ClinicalTrials.gov ID
- NCT00843713
- Acronym / sponsor ID
- 1R01HL095130-01
- Conditions
- HIV Infection, Inflammation, Cardiovascular Disease, HIV Infections
- Keywords
- HIV, endothelium, inflammation, Treatment Experienced
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Merck Sharp & Dohme LLC
- Study start
- Jan 2009
- Primary completion
- Nov 2013 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 13 Feb 2009 (estimated)
- Results
- Posted 10 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent studies suggest that HIV patients are at increased risk for cardiovascular events; however, the mechanisms underlying this increased risk remain unclear. Our group was one of the first to demonstrate that HIV infection is independently associated with accelerated atherosclerosis, as measured by carotid artery-intima media thickness (IMT), and that HIV-associated inflammation may be driving this accelerated atherosclerosis. The mechanism by which HIV disease independent of any drug-specific toxicity increases the risk of cardiovascular disease during HAART is not known. We hypothesize that even well controlled HIV infection is independently associated with cardiovascular risk and that further decreasing HIV-associated inflammation adding newer antiretroviral agents will also decrease cardiovascular risk.
We will perform a small clinical trial of approximately 50 HIV-infected patients each to study the relationship between HIV infection, inflammation, thrombosis, atherogenic lipoproteins, and measures of atherosclerosis. We propose the following specific aims: Aim 1: To determine the influence of traditional and novel markers of inflammation on endothelial function and IMT progression; Aim 2: To determine if "intensification" with raltegravir in subjects on long-term antiretroviral therapy with clinically undetectable HIV RNA levels will improve endothelial function, and to determine if this effect is mediated by alterations in inflammatory markers, lipoproteins and/or thrombotic factors. For Aim 2, subjects from 2 randomized, double-blind, placebo-controlled raltegravir intensification studies will be asked to co-enroll in this cardiovascular study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboFor subjects assigned to the placebo group, patients will take a matching placebo pill of 400 mg by mouth twice daily for 24 weeks in addition to taking their current HIV medication |
| Raltegravir | Active comparator | Drug: raltegravirFor subjects assigned to the active comparator group, they will receive raltegravir at 400 mg by mouth twice daily for 24 weeks in addition to continuing to take their current HIV medication |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Stable antiretroviral therapy for at least 12 months
- All plasma HIV RNA levels within the past year must be below level of detection (< 50 copies RNA/mL), although isolated single values > 50 but < 200 copies will be allowed.
- Screening plasma HIV RNA levels < 50 copies RNA/mL
- >90% adherence to therapy within the preceding 30 days, as determined by self-report
- Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
Key exclusion criteria (7 listed)
- Ongoing or prior use of any integrase inhibitor or R5 inhibitor.
- Patients who plan to modify existing antiretroviral therapy in the next 24 weeks for any reason
- Serious illness requiring hospitalization or parental antibiotics within preceding 3 months
- Concurrent or recent exposure to any immunomodulatory drugs
- Advanced liver disease or active hepatitis B or C
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 |
|---|---|---|
| raltegravirFor patients assigned to the raltegravir group, subjects will receive raltegravir 400mg to be taken by mouth twice daily for 24 weeks in addition to taking their current HIV medication | Drug | Raltegravir |
| PlaceboFor the patient assigned to the placebo group, subjects will take a matching placebo pill 400mg to be taken by mouth twice daily for 24 weeks in addition to taking their current HIV medication | Drug | Placebo |
Primary outcome
Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD)
Time frame: 24 weeks
Measurements in the change of brachial artery diameter from pre and post treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22918156Hatano H, Scherzer R, Wu Y, Harvill K, Maka K, Hoh R, Sinclair E, Palmer S, Martin JN, Busch MP, Deeks SG, Hsue PY. A randomized controlled trial assessing the effects of raltegravir intensification on endothelial function in treated HIV infection. J Acquir Immune Defic Syndr. 2012 Nov 1;61(3):317-25. doi: 10.1097/QAI.0b013e31826e7d0f.
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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.
Priscilla Hsue, MD principal investigator
San Francisco General Hospital
1 site 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 HIV Infection and Inflammation, run by University of California, San Francisco at 1 site in United States.
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 6 inclusion and 7 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: finished, as of the sponsor's last update on 12 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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 10 Jun 2015). 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?
Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD) (time frame: 24 weeks). 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 NCT00843713, which also lists 1 linked publication.
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 12 Dec 2018.