Cardiovascular Prevention for Persons With HIV

• Sponsor: Hennepin Healthcare Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00982189
• Collaborator: American Heart Association (Other)
• Enrollment: 37
• Location: 1
• Arms: 4
• Duration (Months): 19.9
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

This study is funded by the American Heart Association. The goal of this research is to prevent early cardiovascular damage before symptoms develop for persons with HIV infection. Evidence suggests that taking low doses of blood pressure and cholesterol medication reduces risk for heart disease in persons who are at increased risk (such as the case with HIV infection).

Participants who are taking HIV treatment with an 'undetectable' viral load, and who do NOT need treatment for high blood pressure or cholesterol may be eligible to enroll. Participants will take a low dose cholesterol medication (or placebo) and a low dose of a blood pressure medication (or a placebo), and will be seen at 3 study visits over 4 months.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection; Cardiovascular Disease Risk	Drug: Pravastatin; Drug: Lisinopril	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Cardiovascular Disease Risk Reduction for Persons With HIV Infection: a Polypill Pilot Study
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lisinopril Lisinopril 10mg once daily	Drug: Lisinopril; Participants randomized to take lisinopril (active) or matching placebo pill once daily
Placebo Comparator: Lisinopril Placebo Placebo pill (matched to lisinopril) once daily	Drug: Lisinopril; Participants randomized to take lisinopril (active) or matching placebo pill once daily
Experimental: Pravastatin Pravastatin 20mg once daily	Drug: Pravastatin; Participants randomized to take pravastatin (active) or matching placebo pill once daily
Placebo Comparator: Pravastatin placebo Placebo pill (matched to pravastatin) once daily	Drug: Pravastatin; Participants randomized to take pravastatin (active) or matching placebo pill once daily

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Stated (by Self-report) That They Had Side Effects [4 months]

   Participants were asked at each visit if they had any side effects to study medication. They provided a yes or no answer, and if yes they specified what the side effect was.

2. Number of Participants Who Took >90% of Their Doses (by Pill Count) [4 months]

   The number of pills missing from study medication bottles was counted by study nurses at the completion of the study. The proportion of pills taken divided by the number of days the participant was enrolled in the study was calculated, and multiplied by 100, to generate the '% of doses taken'

3. Change From Baseline to Month 4 in the Framingham Risk Score (FRS) [Change from baseline to 4 months]

   The Framingham Risk Score is calculated by a published algorithm that predicts a patients risk of having a coronary heart disease event in the next 10 years. The measures that are considering in predicting this risk are: age, blood pressure, cholesterol (both total cholesterol and high-density lipoprotein cholesterol), smoking status, and use of medication to treat hypertension. This risk score can be estimated using an online calculator (http://hp2010.nhlbihin.net/atpiii/calculator.asp)

Secondary Outcome Measures

1. Changes in Blood Pressure [change from baseline to 4 months]

   Blood pressure was assessed by standard clinical methods (i.e., the same way it is measured during a routine clinic visit)

2. Changes in Blood Lipids [change from baseline to 4 months]

   Blood lipids include routine cholesterol measurements that are monitored in clinical practice. They are measured in blood after a blood draw is performed. The specific measurements include: a) total cholesterol, b) low-density lipoprotein cholesterol, c) high-density lipoprotein cholesterol, and d) triglycerides

3. Changes in Small Artery Elasticity [change from baseline to 4 months]

   Small artery elasticity is a measure of vascular function, estimated through analysis of the blood pressure waveform. A sensor is placed on wrist over the radial pulse. The blood pressure waveform of the pulse is recorded and analyzed the elasticity, or compliance, of the small (and large) vasculature. Impaired artery elasticity, or increased stiffness, is an early sign of vascular disease that predicts risk for future cardiovascular events.

4. Changes hsCRP (C-reactive Protein) [change from baseline to 4 months]

   This biomarker represents systemic inflammation within in the body.

5. Changes IL-6 (Interleukin-6) [change from baseline to 4 months]

   This biomarker represents systemic inflammation within in the body.

6. Changes TNFa (Tumor Necrosis Factor Alpha) [change from baseline to 4 months]

   This biomarker represents systemic inflammation within in the body.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV Infection with viral load 'undetectable' while taking antiretroviral therapy

• Age ≥40

• Framingham risk score (FRS) ≥5%, or ≥3% with ≥5 years of exposure to antiretroviral therapy

Exclusion Criteria:

• Known cardiovascular disease or Framingham risk score (FRS) ≥20%

• Blood pressure ≥140/90

• LDL cholesterol ≥160 (with FRS <10%), or ≥130 (with FRS 10-20%)

• Currently taking, or has a medication contraindication to take, a 'statin', an ACE inhibitor, or an angiotensin receptor blocker medication

• Cirrhosis or plasma ALT/AST levels >2x upper limit of normal

• Chronic kidney disease and a creatinine >2.0mg/dL

• Triglycerides >500mg/dL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415

Sponsors and Collaborators

• Hennepin Healthcare Research Institute
• American Heart Association

Investigators

• Principal Investigator: Jason Baker, MD, Hennepin Faculty Associates

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hennepin Healthcare Research Institute
• ClinicalTrials.gov Identifier: NCT00982189
• Other Study ID Numbers: PCC-003
• First Posted: Sep 23, 2009
• Last Update Posted: Nov 22, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Hennepin Healthcare Research Institute: treatment experienced
• Additional relevant MeSH terms: Infections; HIV Infections; Acquired Immunodeficiency Syndrome; Cardiovascular Diseases; Lisinopril; Pravastatin

Study Results

Participant Flow

Arm/Group Title	Lisinopril/P-placebo	L-placebo/Pravastatin	Lisinopril/Pravastatin	L-placebo/P-placebo
Arm/Group Description	Lisinopril 10mg and placebo (matched to pravastatin) once daily	Placebo pill (matched to lisinopril) and Pravastatin 20mg once daily	Lisinopril 10mg and Pravastatin 20mg once daily	Placebo pill (matched to pravastatin) and placebo pill (matched to lisinopril) once daily
Period Title: Overall Study
STARTED	10	9	9	9
COMPLETED	10	9	9	9
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Lisinopril/P-placebo	L-placebo/Pravastatin	Lisinopril/Pravastatin	L-placebo/P-placebo	Total
Arm/Group Description	Lisinopril 10mg and placebo (matched to pravastatin) once daily	Placebo pill (matched to lisinopril) and Pravastatin 20mg once daily	Lisinopril 10mg and Pravastatin 20mg once daily	Placebo pill (matched to pravastatin) and placebo pill (matched to lisinopril) once daily	Total of all reporting groups
Overall Participants	10	9	9	9	37
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	9 100%	9 100%	9 100%	37 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (8)	47 (12)	48 (4)	45 (7)	48 (7)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 11.1%	0 0%	0 0%	1 2.7%
Male	10 100%	8 88.9%	9 100%	9 100%	36 97.3%
Region of Enrollment (participants) [Number]
United States	10 100%	9 100%	9 100%	9 100%	37 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Stated (by Self-report) That They Had Side Effects
Description	Participants were asked at each visit if they had any side effects to study medication. They provided a yes or no answer, and if yes they specified what the side effect was.
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

Number of participants who stated (by self-report) that they had side effects

Arm/Group Title	Lisinopril/P-placebo	L-placebo/Pravastatin	Lisinopril/Pravastatin	L-placebo/P-placebo
Arm/Group Description	Lisinopril 10mg and placebo (matched to pravastatin) once daily	Placebo pill (matched to lisinopril) and Pravastatin 20mg once daily	Lisinopril 10mg and Pravastatin 20mg once daily	Placebo pill (matched to pravastatin) and placebo pill (matched to lisinopril) once daily
Measure Participants	10	9	9	9
Number [participants]	1 10%	0 0%	2 22.2%	1 11.1%

2. Primary Outcome

Title	Number of Participants Who Took >90% of Their Doses (by Pill Count)
Description	The number of pills missing from study medication bottles was counted by study nurses at the completion of the study. The proportion of pills taken divided by the number of days the participant was enrolled in the study was calculated, and multiplied by 100, to generate the '% of doses taken'
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

Number of participants who took >90% of their doses (by pill count)were studied. All participants who returned unused medications at end of the study were included for these analyses

Arm/Group Title	Lisinopril/P-placebo	L-placebo/Pravastatin	Lisinopril/Pravastatin	L-placebo/P-placebo
Arm/Group Description	Lisinopril 10mg and placebo (matched to pravastatin) once daily	Placebo pill (matched to lisinopril) and Pravastatin 20mg once daily	Lisinopril 10mg and Pravastatin 20mg once daily	Placebo pill (matched to pravastatin) and placebo pill (matched to lisinopril) once daily
Measure Participants	4	7	8	6
Number [participants]	2 20%	7 77.8%	5 55.6%	6 66.7%

3. Primary Outcome

Title	Change From Baseline to Month 4 in the Framingham Risk Score (FRS)
Description	The Framingham Risk Score is calculated by a published algorithm that predicts a patients risk of having a coronary heart disease event in the next 10 years. The measures that are considering in predicting this risk are: age, blood pressure, cholesterol (both total cholesterol and high-density lipoprotein cholesterol), smoking status, and use of medication to treat hypertension. This risk score can be estimated using an online calculator (http://hp2010.nhlbihin.net/atpiii/calculator.asp)
Time Frame	Change from baseline to 4 months

Outcome Measure Data

Analysis Population Description

All participants had Framingham risk score (FRS) estimated at baseline and month 4. The change from baseline to month 4 was calculated as the outcome.

Arm/Group Title	Lisinopril/P-placebo	L-placebo/Pravastatin	Lisinopril/Pravastatin	L-placebo/P-placebo
Arm/Group Description	Lisinopril 10mg and placebo (matched to pravastatin) once daily	Placebo pill (matched to lisinopril) and Pravastatin 20mg once daily	Lisinopril 10mg and Pravastatin 20mg once daily	Placebo pill (matched to pravastatin) and placebo pill (matched to lisinopril) once daily
Measure Participants	10	9	9	9
Median (Inter-Quartile Range) [Percent probability of CHD event in 10yr]	-1.6	-0.7	-1.5	-0.3

4. Secondary Outcome

Title	Changes in Blood Pressure
Description	Blood pressure was assessed by standard clinical methods (i.e., the same way it is measured during a routine clinic visit)
Time Frame	change from baseline to 4 months

Outcome Measure Data

Analysis Population Description

n=17 Lisinopril vs. n=17 L-placebo The outcome is analyzed as the 'main effect' for lisinopril versus placebo, as standard for factorial study designs. Since lisinopril, but not pravastatin, influences blood pressure, the analysis defines Lisinopril and L-placebo groups by pooling across pravastatin groups (i.e., P-placebo + Pravastatin groups).

Arm/Group Title	Lisinopril/L-placebo Treatment Effect
Arm/Group Description	Lisinopril vs. Lisinopril-placebo (regardless of Pravastatin status)
Measure Participants	34
Systolic BP	-1.8
Diastolic BP	-3.3

5. Secondary Outcome

Title	Changes in Blood Lipids
Description	Blood lipids include routine cholesterol measurements that are monitored in clinical practice. They are measured in blood after a blood draw is performed. The specific measurements include: a) total cholesterol, b) low-density lipoprotein cholesterol, c) high-density lipoprotein cholesterol, and d) triglycerides
Time Frame	change from baseline to 4 months

Outcome Measure Data

Analysis Population Description

n = 18 Pravastatin vs. n = 16 P-placebo The outcome is analyzed as the 'main effect' for pravastatin versus placebo, as standard for factorial study designs. Since pravastatin, but not lisinopril, influences cholesterol, the analysis defines Pravastatin and P-placebo groups by pooling across lisinopril groups (i.e., L-placebo + Lisinopril group).

Arm/Group Title	Pravastatin/P-placebo Treatment Effect
Arm/Group Description	Pravastatin vs. Pravastatin-placebo (regardless of Lisinopril status)
Measure Participants	34
Total Cholesterol	-1.75
LDL-C	-0.62
HDL-C	0.97

6. Secondary Outcome

Title	Changes in Small Artery Elasticity
Description	Small artery elasticity is a measure of vascular function, estimated through analysis of the blood pressure waveform. A sensor is placed on wrist over the radial pulse. The blood pressure waveform of the pulse is recorded and analyzed the elasticity, or compliance, of the small (and large) vasculature. Impaired artery elasticity, or increased stiffness, is an early sign of vascular disease that predicts risk for future cardiovascular events.
Time Frame	change from baseline to 4 months

Outcome Measure Data

Analysis Population Description

Analysis presents the baseline-to-month4 difference between Lisinopril versus L-placebo groups; n=17 Lisinopril vs. n=17 L-placebo Our hypothesis for this secondary outcome was the 'main effect' for Lisinopril versus placebo would reduce inflammation. There was no interaction, so analyses define Lisinopril and L-placebo groups as for outcome #4

Arm/Group Title	Lisinopril/L-placebo Treatment Effect
Arm/Group Description	Lisinopril vs. Lisinopril-placebo (regardless of Pravastatin status)
Measure Participants	34
Mean (Standard Error) [mL/mmHgx100]	0.02 (0.75)

7. Secondary Outcome

Title	Changes hsCRP (C-reactive Protein)
Description	This biomarker represents systemic inflammation within in the body.
Time Frame	change from baseline to 4 months

Outcome Measure Data

Analysis Population Description

Analysis presents the baseline-to-month4 difference between Lisinopril versus L-placebo groups; n=17 Lisinopril vs. n=17 L-placebo Our hypothesis for this secondary outcome was the 'main effect' for Lisinopril versus placebo would reduce inflammation. There was no interaction, so analyses define Lisinopril and L-placebo groups as for outcome #4

Arm/Group Title	Lisinopril/L-placebo Treatment Effect
Arm/Group Description	Lisinopril vs. Lisinopril-placebo (regardless of Pravastatin status)
Measure Participants	34
Geometric Mean (Standard Error) [mcg/mL]	-1.00 (0.40)

8. Secondary Outcome

Title	Changes IL-6 (Interleukin-6)
Description	This biomarker represents systemic inflammation within in the body.
Time Frame	change from baseline to 4 months

Outcome Measure Data

Analysis Population Description

Analysis presents the baseline-to-month4 difference between Lisinopril versus L-placebo groups; n=17 Lisinopril vs. n=17 L-placebo Our hypothesis for this secondary outcome was the 'main effect' for Lisinopril versus placebo would reduce inflammation. There was no interaction, so analyses define Lisinopril and L-placebo groups as for outcome #4

Arm/Group Title	Lisinopril/L-placebo Treatment Effect
Arm/Group Description	Lisinopril vs. Lisinopril-placebo (regardless of Pravastatin status)
Measure Participants	34
Geometric Mean (Standard Error) [pg/mL]	-0.33 (0.24)

9. Secondary Outcome

Title	Changes TNFa (Tumor Necrosis Factor Alpha)
Description	This biomarker represents systemic inflammation within in the body.
Time Frame	change from baseline to 4 months

Outcome Measure Data

Analysis Population Description

Analysis presents the baseline-to-month4 difference between Lisinopril versus L-placebo groups; n=17 Lisinopril vs. n=17 L-placebo Our hypothesis for this secondary outcome was the 'main effect' for Lisinopril versus placebo would reduce inflammation. There was no interaction, so analyses define Lisinopril and L-placebo groups as for outcome #4

Arm/Group Title	Lisinopril/L-placebo Treatment Effect
Arm/Group Description	Lisinopril vs. Lisinopril-placebo (regardless of Pravastatin status)
Measure Participants	34
Geometric Mean (Standard Error) [pg/mL]	-0.14 (0.10)

Adverse Events

Arm/Group Title	Lisinopril/P-placebo		L-placebo/Pravastatin		Lisinopril/Pravastatin		L-placebo/P-placebo
Arm/Group Description	Lisinopril 10mg and placebo (matched to pravastatin) once daily		Placebo pill (matched to lisinopril) and Pravastatin 20mg once daily		Lisinopril 10mg and Pravastatin 20mg once daily		Placebo pill (matched to pravastatin) and placebo pill (matched to lisinopril) once daily
All Cause Mortality
	Lisinopril/P-placebo		L-placebo/Pravastatin		Lisinopril/Pravastatin		L-placebo/P-placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lisinopril/P-placebo		L-placebo/Pravastatin		Lisinopril/Pravastatin		L-placebo/P-placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)		0/9 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Lisinopril/P-placebo		L-placebo/Pravastatin		Lisinopril/Pravastatin		L-placebo/P-placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)

Limitations/Caveats

Study was small with limited power to detect differences.

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.