Effect of Raltegravir on Endothelial Function in HIV-Infected Patients

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT00843713
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Merck Sharp & Dohme LLC (Industry)
• Enrollment: 56
• Location: 1
• Arms: 2
• Duration (Months): 61
• Patients Per Site Per Month: 0.9

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection; Inflammation; Cardiovascular Disease; HIV Infections	Drug: raltegravir; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled Trial Assessing the Effects of Raltegravir Intensification on Endothelial Function in Treated HIV Infection
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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	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
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	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

Outcome Measures

Primary Outcome Measures

1. Endothelial Function Measured by Brachial Artery Flow-mediated Dilation(FMD) [24 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94110

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Priscilla Hsue, MD, San Francisco General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Priscilla Hsue, Associate Professor, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00843713
• Other Study ID Numbers: 1R01HL095130-01
• First Posted: Feb 13, 2009
• Last Update Posted: Dec 12, 2018
• Last Verified: Dec 1, 2018

• Keywords provided by Priscilla Hsue, Associate Professor, University of California, San Francisco: HIV; endothelium; inflammation; Treatment Experienced
• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Cardiovascular Diseases; Inflammation; Raltegravir Potassium

Study Results

Participant Flow

Arm/Group Title	Placebo	Raltegravir
Arm/Group 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 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	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 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
Period Title: Overall Study
STARTED	30	26
COMPLETED	30	26
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Raltegravir	Total
Arm/Group 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 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	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 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	Total of all reporting groups
Overall Participants	30	26	56
Age (Years) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [Years]	53	54	53
Sex: Female, Male (Count of Participants)
Female	1 3.3%	2 7.7%	3 5.4%
Male	29 96.7%	24 92.3%	53 94.6%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	19 63.3%	20 76.9%	39 69.6%
African-American	5 16.7%	3 11.5%	8 14.3%
Latino	2 6.7%	1 3.8%	3 5.4%
Other	4 13.3%	2 7.7%	6 10.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Raltegravir
Arm/Group 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 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	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 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
Measure Participants	30	26
Median (Inter-Quartile Range) [millimeters]	3.4	2.9

Adverse Events

Arm/Group Title	Placebo		Raltegravir
Arm/Group 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 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		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 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
All Cause Mortality
	Placebo		Raltegravir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Raltegravir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		1/26 (3.8%)
Hepatobiliary disorders
Hepatocellular Carcinoma	0/30 (0%)		1/26 (3.8%)
Infections and infestations
Infection	1/30 (3.3%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Raltegravir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		1/26 (3.8%)
Hepatobiliary disorders
Hyperbilirubinemia	0/30 (0%)		1/26 (3.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.