Effect of Raltegravir on Endothelial Function in HIV-Infected Patients

NCT00843713 | Completed Phase 4 Results DMC

• 1 other identifier: 1R01HL095130-01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infection; Inflammation; Cardiovascular Disease; HIV Infections

Keywords

HIV; endothelium; inflammation; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD)

  Measurements in the change of brachial artery diameter from pre and post treatment.

  24 weeks

Study Arms (2)

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

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

Drug: raltegravir

Interventions

raltegravir DRUG

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

Raltegravir

Placebo DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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").

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94110, United States

Location

Related Publications (1)

• 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.

  PMID: 22918156 DERIVED

MeSH Terms

Conditions

HIV Infections; Inflammation; Cardiovascular Diseases

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Priscilla Hsue, MD
• Organization: University of California, San Francisco

Priscilla.Hsue@ucsf.edu

415-206-8257

Study Officials

• Priscilla Hsue, MD

  San Francisco General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 12, 2009
• First Posted: February 13, 2009
• Study Start: January 1, 2009
• Primary Completion: November 1, 2013
• Study Completion: February 1, 2014
• Last Updated: December 12, 2018
• Results First Posted: June 10, 2015

Record last verified: 2018-12

Locations

US (1)