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Effect of Raltegravir on Endothelial Function in HIV-Infected Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Priscilla Hsue, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00843713
First received: February 12, 2009
Last updated: November 7, 2013
Last verified: November 2013

February 12, 2009
November 7, 2013
January 2009
November 2013   (final data collection date for primary outcome measure)
  • endothelial function [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Primary virologic outcome: Increase in 2-LTR circles at weeks 1 or 2 (immunologic responders, n=31) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00843713 on ClinicalTrials.gov Archive Site
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Effect of Raltegravir on Endothelial Function in HIV-Infected Patients
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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.

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Interventional
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Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • HIV Infection
  • Inflammation
  • Cardiovascular Disease
  • HIV Infections
  • Drug: raltegravir
    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
  • Drug: Placebo
    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
  • Placebo Comparator: Placebo
    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
    Intervention: Drug: Placebo
  • Active Comparator: Raltegravir
    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
    Intervention: Drug: raltegravir
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
50
February 2014
November 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Stable antiretroviral therapy for at least 12 months
  2. 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.
  3. Screening plasma HIV RNA levels < 50 copies RNA/mL
  4. >90% adherence to therapy within the preceding 30 days, as determined by self-report
  5. 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.
  6. CD4<350 cells/mm3 for at least one year ("immunologic non-responder") or CD4>=350 cells/mm3 for at least one year ("immunologic responder").

Exclusion Criteria:

  1. Ongoing or prior use of any integrase inhibitor or R5 inhibitor.
  2. Patients who plan to modify existing antiretroviral therapy in the next 24 weeks for any reason
  3. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months
  4. Concurrent or recent exposure to any immunomodulatory drugs
  5. Advanced liver disease or active hepatitis B or C
  6. Patients with systolic blood pressure <100/70
  7. Starting or stopping statin therapy during the trial
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00843713
1R01HL095130-01, 1R01HL095130-01
Yes
Priscilla Hsue, University of California, San Francisco
University of California, San Francisco
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Merck Sharp & Dohme Corp.
Principal Investigator: Priscilla Hsue, MD San Francisco General Hospital
University of California, San Francisco
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP