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Effect of Raltegravir on Endothelial Function in HIV-Infected Patients

Primary Purpose

HIV Infection, Inflammation, Cardiovascular Disease

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
raltegravir
Placebo
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infection focused on measuring HIV, endothelium, inflammation, Treatment Experienced

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, San Francisco

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Raltegravir

Arm Description

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

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

Outcomes

Primary Outcome Measures

Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD)
Measurements in the change of brachial artery diameter from pre and post treatment.

Secondary Outcome Measures

Full Information

First Posted
February 12, 2009
Last Updated
December 10, 2018
Sponsor
University of California, San Francisco
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00843713
Brief Title
Effect of Raltegravir on Endothelial Function in HIV-Infected Patients
Official Title
A Randomized, Controlled Trial Assessing the Effects of Raltegravir Intensification on Endothelial Function in Treated HIV Infection
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Francisco
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection, Inflammation, Cardiovascular Disease, HIV Infections
Keywords
HIV, endothelium, inflammation, Treatment Experienced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Raltegravir
Arm Type
Active Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
raltegravir
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD)
Description
Measurements in the change of brachial artery diameter from pre and post treatment.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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"). Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Priscilla Hsue, MD
Organizational Affiliation
San Francisco General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22918156
Citation
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.
Results Reference
derived

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Effect of Raltegravir on Endothelial Function in HIV-Infected Patients

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