Endothelial Function, Lipoproteins, and Inflammation With Low HDL Cholesterol in HIV: ER Niacin Versus Fenofibrate

• Sponsor: AIDS Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01426438
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 99
• Locations: 14
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study is being done with people with HIV infection who have low levels of HDL-C. HDL-C is a type of "good" cholesterol. People with low HDL-C have a higher risk of heart disease and may have problems with how their blood vessels relax. The endothelium is the inner lining of all blood vessels, such as arteries and veins. When the endothelium is not working properly, the blood vessels have trouble expanding properly, which contributes to the development of heart and blood vessel disease.

The main purpose of this study is to see if taking either extended-release niacin or fenofibrate for 24 weeks will help blood vessels work better by improving endothelial function and increasing HDL-C. Niacin and fenofibrate are medications that raise HDL-C. This study will also help determine how safe extended-release niacin and fenofibrate are.

The analysis is an as-treated analysis of participants who completed study treatment and had a week 24 BART scan. Safety analyses include all participants

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: Niacin; Drug: Aspirin; Drug: Fenofibrate	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of HDL-Raising Therapies on Endothelial Function, Lipoproteins, and Inflammation in HIV-infected Subjects With Low HDL Cholesterol: A Phase II Randomized Trial of Extended Release Niacin vs. Fenofibrate
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Extended-release niacin with aspirin	Drug: Niacin; Extended-release niacin will be given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24); Drug: Aspirin; Aspirin 325 mg will be given by mouth in the evening with extended-release niacin through week 24.
Experimental: Arm B: Fenofibrate	Drug: Fenofibrate; Fenofibrate will be administered as 200 mg by mouth once daily for 24 weeks.

Outcome Measures

Primary Outcome Measures

1. Absolute Change in Relative FMD (%) [0 and 24 weeks]

   The absolute change in maximum relative flow mediated dilation (FMD) (%) of the brachial artery from baseline to week 24.

Secondary Outcome Measures

1. Change in Cholesterol [0 and 24 weeks]

   Absolute change in total cholesterol from week 0 to week 24.

2. Change in Triglycerides [0 and 24 weeks]

   Change in Triglycerides (mg/dL) from week 0 to week 24.

3. Men: Change in HDL Cholesterol [0 and 24 weeks]

   Among men, change in HDL Cholesterol (mg/dL) from week 0 to week 24.

4. Women: Change in HDL Cholesterol [0 and 24 weeks]

   Among women, change in HDL cholesterol (mg/dL) from week 0 to week 24.

5. Change in HDL Particles [0 and 24 weeks]

   Change in total HDL particles from week 0 to week 24

6. Change in Non-HDL Cholesterol [0 and 24 weeks]

   Change in non-HDL Cholesterol (mg/dL) from week 0 to week 24.

7. Change in LDL Cholesterol [0 and 24 weeks]

   Change in LDL cholesterol (mg/dL) from week 0 to week 24.

8. Change in Small LDL Particles [0 and 24 weeks]

   Change in Small LDL particles from week 0 to week 24.

9. Change in Large HDL Particles [0 and 24 weeks]

   Change in Large HDL Particles from week 0 to week 24

10. Change in HOMA-IR [0 and 24 weeks]

    Absolute change from week 0 to week 24 in insulin resistance as estimated by HOMA-IR

11. Change in IL-6 [0 and 24 weeks]

    Change in IL-6 from week 0 to week 24

12. Change in C-reactive Protein (CRP) [0 and 24 weeks]

    Change in C-reactive protein from week 0 to week 24.

13. Change in D-Dimer [0 and 24 weeks]

    Change in D-Dimer from week 0 to week 24

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• HIV-1 infection

• Currently on continuous ART for ≥48 weeks.

• CD4+ cell count ≥100/mm3 obtained within 60 days prior to study entry.

• Most recent HIV-1 RNA below the limit of detection using an ultrasensitive licensed or FDA-approved assay obtained within 60 days prior to study entry.

• Certain laboratory values obtained within 60 days prior to study entry (as indicated in the protocol).

• HDL-C ≤ 40 mg/dL for men or ≤ 50 mg/dL for women within 60 days prior to study entry by any local assay.

• Fasting triglycerides 150-800 mg/dL within 60 days prior to study entry, (initially 200-800 mg/dL, amended during study conduct).

• LDL-C < 160 mg/dL within 60 days prior to study entry.

• For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of 15-25 mIU/mL within 60 days prior to entry.

• Female subjects of reproductive potential must agree to use a reliable method of contraception while receiving study drug and for 6 weeks after stopping study drug.

Exclusion Criteria:

• Anticipation of changing ART.

• Intent to initiate or change the dose of lipid-lowering drugs or antihypertensives during study.

• Active acute infection or other serious illness requiring systemic treatment and/or hospitalization until subject either completes or is clinically stable on therapy in the opinion of the site investigator.

• Untreated hypogonadism

• History of physician-diagnosed diabetes mellitus or currently taking glucose-lowering medication, (amended during study conduct to allow well-controlled diabetics who are diet controlled or on stable antidiabetic treatment of metformin, sulfonylurea, meglitinides or alpha-glucosidase inhibitors).

• Hormonal anabolic therapies within 90 days prior to study entry.

• Uncontrolled hypertension within 60 days of study entry.

• Acute symptoms of gout within 60 days prior to study entry.

• Active peptic ulcer disease as defined by a health care professional. Treatment for gastroesophageal reflux disease (GERD) is not exclusionary.

• Documented untreated hypothyroidism per subject's medical records.

• Use of thyroid hormone supplements other than for treatment of hypothyroidism within 30 days prior to entry.

• Active or symptomatic gallbladder disease within 1 year of study entry.

• Active cancer requiring systemic chemotherapy or radiation within 1 year of study entry.

• Lipid-lowering agents within 30 days prior to study entry.

• Use of fish oil with DHA/EPA >1000 mg/day within 30 days prior to entry.

• Niacin or niacin-containing products that contain >100 mg daily within 30 days prior to study entry.

• Use of vitamin E supplements greater than 200 IU/day within 30 days prior to entry.

• Use of vitamin C supplements greater than 250 mg/day within 30 days prior to entry.

• Use of systemic cancer chemotherapy, immunomodulators (e.g., growth factors, immune globulin, interleukins, and interferons) within 90 days prior to study entry.

• Any systemic glucocorticoid above replacement levels, defined as the equivalent of ≥ 7.5 mg of prednisone daily, within 60 days prior to study entry.

• Allergy, sensitivity, or severe intolerance to both aspirin and naproxen (Aleve, Naprosyn).

• Symptomatic pancreatitis with hospitalization.

• Pregnancy or currently breastfeeding.

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

• Currently taking or anticipation of starting medication during the study for hepatitis C including interferon and ribavirin.

• Documented history of macular edema.

• Current severe congestive heart failure (New York Heart Association [NYHA] Class III or IV).

• History of or current diagnosis of coronary artery disease, angina pectoris, myocardial infarction, previous coronary artery intervention (stenting, angioplasty), peripheral arterial disease (claudication, peripheral arterial angioplasty, or peripheral arterial bypass procedure), cerebrovascular disease (stroke or transient ischemic attack with documented carotid or aortic atherosclerosis), or abdominal aortic aneurysm.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS (5801)	Birmingham	Alabama	United States	35294
2	University of Southern California (1201)	Los Angeles	California	United States	90033-1079
3	UCLA CARE Center CRS (601)	Los Angeles	California	United States	90095
4	Harbor-UCLA Med. Ctr. CRS (603)	Torrance	California	United States	90502
5	University of Colorado Hospital CRS (6101)	Aurora	Colorado	United States	80045
6	Northwestern University CRS (2701)	Chicago	Illinois	United States	60611
7	New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)	Newark	New Jersey	United States	07103
8	NY Univ. HIV/AIDS CRS (401)	New York	New York	United States	10016
9	Unc Aids Crs (3201)	Chapel Hill	North Carolina	United States	27516
10	Duke Univ. Med. Ctr. Adult CRS (1601)	Durham	North Carolina	United States	27710
11	Moses H. Cone Memorial Hospital CRS (3203)	Greensboro	North Carolina	United States	27401
12	Univ. of Cincinnati CRS (2401)	Cincinnati	Ohio	United States	45267
13	Case CRS (2501)	Cleveland	Ohio	United States	44106
14	University of Washington AIDS CRS (1401)	Seattle	Washington	United States	98104

Sponsors and Collaborators

• AIDS Clinical Trials Group
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Michael P Dube, MD, University of Southern California
• Study Chair: James H Stein, MD, University of Wisconsin School of Medicine and Public Health (Northwestern University CRS)

Study Documents (Full-Text)

None provided.

More Information

Publications

• International Conference on Harmonisation. E2A: Clinical Safety Data Management : Definitions and Standards for Expedited Reporting. Website: http://www.ich.org/products/guidelines/efficacy/efficacy-single/article/clinical-safety-data-management-definitions-and-standards-for-expedited-reporting.html. Accessed May 24, 2011.

• Responsible Party: AIDS Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT01426438
• Other Study ID Numbers: ACTG A5293; 1U01AI068636
• First Posted: Aug 31, 2011
• Last Update Posted: Feb 3, 2016
• Last Verified: Jan 1, 2016

• Additional relevant MeSH terms: Inflammation; Aspirin; Niacin; Fenofibrate

Study Results

Participant Flow

Recruitment Details	A5293 opened to accrual under protocol version 1.0 on November 8, 2011. The first participant was enrolled on January 10, 2012. Accrual to the study closed on April 24, 2013, with a total of 99 participants enrolled from 11 sites within the US.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Period Title: Overall Study
STARTED	50	49
COMPLETED	35	39
NOT COMPLETED	15	10

Baseline Characteristics

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate	Total
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.	Total of all reporting groups
Overall Participants	35	39	74
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	35 100%	39 100%	74 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	46	45	45
Sex: Female, Male (Count of Participants)
Female	8 22.9%	9 23.1%	17 23%
Male	27 77.1%	30 76.9%	57 77%
Race/Ethnicity, Customized (participants) [Number]
White, non-Hispanic	15 42.9%	15 38.5%	30 40.5%
Black, non-Hispanic	5 14.3%	6 15.4%	11 14.9%
Hispanic, regardless of race	15 42.9%	17 43.6%	32 43.2%
American Indian, Alaskan Native	0 0%	1 2.6%	1 1.4%
Region of Enrollment (participants) [Number]
United States	35 100%	39 100%	74 100%
Current Smoker (participants) [Number]
Yes	10 28.6%	16 41%	26 35.1%
No	25 71.4%	23 59%	48 64.9%
10 year Coronary Heart Disease (CHD) risk (10yr Framingham CHD risk (%)) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [10yr Framingham CHD risk (%)]	3	3	3
Relative FMD (%) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [%]	4.38	3.93	4.21
Baseline Cholesterol (mg/dL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mg/dL]	185	184	184
Triglycerides (mg/dL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mg/dL]	254	206	232
High Density Lipoprotein (HDL)-Cholesterol (participants) [Number]
Very low HDL-C (< 30 mg/dL (Men)/< 40 mg/dL (W))	10 28.6%	12 30.8%	22 29.7%
Low HDL-C (30-40 mg/dL (Men)/40-50 mg/dL (Women))	25 71.4%	27 69.2%	52 70.3%
Men: HDL Cholesterol (mg/dL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mg/dL]	32	36	33
Women: HDL Cholesterol (mg/dL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mg/dL]	37	38	38
HDL Particles (nmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [nmol/L]	31.8	30.2	31.3
Non-HDL Cholesterol (mg/dL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mg/dL]	150	153	150
Low Density Lipoprotein (LDL) Cholesterol (mg/dL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mg/dL]	103	101	103
Small LDL Particles (nmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [nmol/L]	1018	1052	1022
Large HDL Particles (nmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [nmol/L]	2.1	2.6	2.5
HOMA-IR (Homeostatic model assessment - Insulin Resistance) (HOMA IR Score) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [HOMA IR Score]	2.5	3.2	3.1
Interleukin(IL)-6 (pg/ml) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [pg/ml]	1.1	1.5	1.3
C-reactive protein (ug/ml) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ug/ml]	1.9	1.5	1.7
D-Dimer (ug/ml) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ug/ml]	0.30	0.25	0.29

Outcome Measures

1. Primary Outcome

Title	Absolute Change in Relative FMD (%)
Description	The absolute change in maximum relative flow mediated dilation (FMD) (%) of the brachial artery from baseline to week 24.
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	35	39
Median (Inter-Quartile Range) [% FMD]	0.60	0.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Extended-release Niacin With Aspirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Sign test
	Comments	Stratified exact Wilcoxon signed rank test. Stratified by screening HDL-C level and statin use within 90 days prior to study entry.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B: Fenofibrate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Sign test
	Comments	Stratified exact Wilcoxon signed rank test. Stratified by screening HDL-C level and statin use within 90 days prior to study entry.

2. Secondary Outcome

Title	Change in Cholesterol
Description	Absolute change in total cholesterol from week 0 to week 24.
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan and had lipid panels at weeks 0 and 24.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	34	39
Median (Inter-Quartile Range) [mg/dL]	-9	-2

3. Secondary Outcome

Title	Change in Triglycerides
Description	Change in Triglycerides (mg/dL) from week 0 to week 24.
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	34	39
Median (Inter-Quartile Range) [mg/dL]	-65	-54

4. Secondary Outcome

Title	Men: Change in HDL Cholesterol
Description	Among men, change in HDL Cholesterol (mg/dL) from week 0 to week 24.
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

Men in the as-treated analysis population, limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	27	30
Median (Inter-Quartile Range) [mg/dL]	3	6.5

5. Secondary Outcome

Title	Women: Change in HDL Cholesterol
Description	Among women, change in HDL cholesterol (mg/dL) from week 0 to week 24.
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

Women in the as-treated analysis population, limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	7	9
Median (Inter-Quartile Range) [mg/dL]	16	8

6. Secondary Outcome

Title	Change in HDL Particles
Description	Change in total HDL particles from week 0 to week 24
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	35	39
Median (Inter-Quartile Range) [nmol/L]	-1.7	4.3

7. Secondary Outcome

Title	Change in Non-HDL Cholesterol
Description	Change in non-HDL Cholesterol (mg/dL) from week 0 to week 24.
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	34	39
Median (Inter-Quartile Range) [mg/dL]	-17	-4

8. Secondary Outcome

Title	Change in LDL Cholesterol
Description	Change in LDL cholesterol (mg/dL) from week 0 to week 24.
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	27	35
Median (Inter-Quartile Range) [mg/dL]	-1	7

9. Secondary Outcome

Title	Change in Small LDL Particles
Description	Change in Small LDL particles from week 0 to week 24.
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	35	39
Median (Inter-Quartile Range) [nmol/L]	-176	-119

10. Secondary Outcome

Title	Change in Large HDL Particles
Description	Change in Large HDL Particles from week 0 to week 24
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	35	39
Median (Inter-Quartile Range) [nmol/L]	0.9	-0.3

11. Secondary Outcome

Title	Change in HOMA-IR
Description	Absolute change from week 0 to week 24 in insulin resistance as estimated by HOMA-IR
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	34	35
Median (Inter-Quartile Range) [HOMA IR Score]	1.3	0.3

12. Secondary Outcome

Title	Change in IL-6
Description	Change in IL-6 from week 0 to week 24
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	32	33
Median (Inter-Quartile Range) [pg/ml]	0.1	0.2

13. Secondary Outcome

Title	Change in C-reactive Protein (CRP)
Description	Change in C-reactive protein from week 0 to week 24.
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	35	39
Median (Inter-Quartile Range) [ug/ml]	-0.6	0.7

14. Secondary Outcome

Title	Change in D-Dimer
Description	Change in D-Dimer from week 0 to week 24
Time Frame	0 and 24 weeks

Outcome Measure Data

Analysis Population Description

This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.

Arm/Group Title	Arm A: Extended-release Niacin With Aspirin	Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.	Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
Measure Participants	35	39
Median (Inter-Quartile Range) [ug/ml]	0.06	0.06

Adverse Events

Time Frame	Adverse event data were collected from randomization to the date the participant went off study.
Adverse Event Reporting Description	Grade≥2 nausea, vomiting diarrhea, ulcers, abnormal bleeding/bruising, and lab values. Other Grade≥3 signs/symptoms and all s/sx or labs that lead to a change in study treatment regardless of grade. Diagnoses per ACTG criteria for clinical events & diseases. See DAIDS Table for Grading the Severity of Adult and pediatric AEs, V1.0.
Arm/Group Title	Arm A: Extended-release Niacin With Aspirin		Arm B: Fenofibrate
Arm/Group Description	Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24) Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24.		Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks.
All Cause Mortality
	Arm A: Extended-release Niacin With Aspirin		Arm B: Fenofibrate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A: Extended-release Niacin With Aspirin		Arm B: Fenofibrate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/50 (2%)		0/49 (0%)
Gastrointestinal disorders
Pancreatitis	1/50 (2%)		0/49 (0%)
Other (Not Including Serious) Adverse Events
	Arm A: Extended-release Niacin With Aspirin		Arm B: Fenofibrate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/50 (94%)		34/49 (69.4%)
Gastrointestinal disorders
Abdominal pain	3/50 (6%)		1/49 (2%)
Diarrhoea	3/50 (6%)		0/49 (0%)
Nausea	7/50 (14%)		2/49 (4.1%)
Vomiting	4/50 (8%)		1/49 (2%)
General disorders
Fatigue	3/50 (6%)		0/49 (0%)
Investigations
Alanine aminotransferase increased	8/50 (16%)		7/49 (14.3%)
Aspartate aminotransferase increased	10/50 (20%)		4/49 (8.2%)
Blood alkaline phosphatase increased	7/50 (14%)		0/49 (0%)
Blood bilirubin increased	17/50 (34%)		8/49 (16.3%)
Blood cholesterol increased	11/50 (22%)		12/49 (24.5%)
Blood creatinine increased	1/50 (2%)		8/49 (16.3%)
Blood glucose decreased	1/50 (2%)		5/49 (10.2%)
Blood glucose increased	13/50 (26%)		6/49 (12.2%)
Blood phosphorus decreased	2/50 (4%)		4/49 (8.2%)
Blood triglycerides increased	2/50 (4%)		3/49 (6.1%)
Blood uric acid increased	9/50 (18%)		1/49 (2%)
Low density lipoprotein increased	5/50 (10%)		5/49 (10.2%)
Musculoskeletal and connective tissue disorders
Myalgia	5/50 (10%)		3/49 (6.1%)
Pain in extremity	4/50 (8%)		2/49 (4.1%)
Nervous system disorders
Paraesthesia	3/50 (6%)		0/49 (0%)
Skin and subcutaneous tissue disorders
Pruritus generalised	3/50 (6%)		0/49 (0%)
Vascular disorders
Flushing	15/50 (30%)		0/49 (0%)

Limitations/Caveats

[Not Specified]

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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.