Trial Outcomes & Findings for Effects of Eplerenone on Cardiovascular Disease in HIV (MIRACLE HIV Study) (NCT NCT02740179)

Results Overview

Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by coronary flow reserve measured via cardiac positron emission tomography. Coronary flow reserve is given by the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

40 participants

Primary outcome timeframe

12 Months

Results posted on

2023-06-06

Participant Flow

Participant milestones

Participant milestones
Measure	Eplerenone Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Overall Study STARTED	20	20
Overall Study COMPLETED	14	19
Overall Study NOT COMPLETED	6	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effects of Eplerenone on Cardiovascular Disease in HIV (MIRACLE HIV Study)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eplerenone n=20 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=20 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Total n=40 Participants Total of all reporting groups
Age, Continuous	53 years STANDARD_DEVIATION 7 • n=5 Participants	56 years STANDARD_DEVIATION 6 • n=7 Participants	55 years STANDARD_DEVIATION 7 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by coronary flow reserve measured via cardiac positron emission tomography. Coronary flow reserve is given by the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest.

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Myocardial Perfusion by PET	0.01 unitless Standard Deviation 0.64	-0.07 unitless Standard Deviation 0.48

PRIMARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by myocardial blood flow measured via cardiac magnetic resonance imaging

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Myocardial Perfusion by MRI	0.09 mL/min/g Standard Deviation 0.56	-0.53 mL/min/g Standard Deviation 0.68

PRIMARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in myocardial inflammation measured by extracellular mass index (a measure of the inflammation within the heart) via cardiac magnetic resonance imaging

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Myocardial Inflammation	0.9 g/m^2 Interval -2.3 to 4.3	-0.7 g/m^2 Interval -2.2 to -0.1

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in coronary plaque measured via coronary computed tomography angiogram assessed by coronary calcium score Scale: minimum 0 to maximum no limit, higher score indicates more plaque

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Coronary Plaque	0 score on a scale Interval 0.0 to 6.0	5 score on a scale Interval 0.0 to 41.0

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in serum hs-cTnT

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Markers of Vascular Dysfunction	0.00 ng/L Interval -0.13 to 0.0	0.00 ng/L Interval 0.0 to 0.74

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in plasma hsIL-6

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Markers of Systemic Inflammation hsIL-6	-0.8 pg/mL Interval -1.8 to 0.4	0.2 pg/mL Interval -0.5 to 2.2

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in plasma hsCRP

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Markers of Systemic Inflammation hsCRP	189 ng/mL Interval -3841.0 to 718.0	591 ng/mL Interval -261.0 to 2346.0

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in plasma MCP-1

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Markers of Immune Activation MCP-1	285 pg/mL Interval 49.0 to 365.0	292 pg/mL Interval 241.0 to 352.0

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in plasma sCD163

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Markers of Immune Activation sCD163	-275 ng/mL Interval -384.0 to -11.0	-160 ng/mL Interval -304.0 to 100.0

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in serum NT-proBNP

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Markers of Subclinical Injury	19.4 ng/L Interval 6.6 to 41.0	2.8 ng/L Interval -25.6 to 63.5

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in myocardial fibrosis measured by T1 (a signal intensity that measures fibrosis) via cardiac magnetic resonance imaging

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Markers of Fibrosis	25 ms Interval 5.0 to 74.0	1 ms Interval -50.0 to 85.0

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available as part of a substudy.

Percentage change (value at 12 months minus value at baseline) in target to background ratio (a measure of arterial inflammation) of the index vessel measured via positron emission tomography/computed tomography

Outcome measures

Outcome measures
Measure	Eplerenone n=13 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=13 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Arterial Inflammation	-12.4 percentage change Interval -21.9 to -2.6	5.1 percentage change Interval -1.6 to 11.0

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available as part of a substudy.

Change (value at 12 months minus value at baseline) in plasma LpPLA2

Outcome measures

Outcome measures
Measure	Eplerenone n=13 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=13 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Markers of Arterial Inflammation	3.0 ng/mL Interval -6.6 to 25.0	2.6 ng/mL Interval -10.1 to 9.5

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in left ventricular mass on cardiac magnetic resonance imaging

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Assessment of Cardiac Structure by Left Ventricular Mass on Cardiac Imaging	1 g Interval -25.0 to 26.0	9 g Interval -3.0 to 17.0

SECONDARY outcome

Timeframe: 12 Months

Population: Analyses performed on data available

Change (value at 12 months minus value at baseline) in global circumferential strain (GCS) on cardiac magnetic resonance imaging

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Assessment of Cardiac Systolic Function Via Cardiac Imaging	-1.3 percentage GCS Interval -2.9 to 1.0	2.3 percentage GCS Interval -0.4 to 4.1

SECONDARY outcome

Timeframe: 12 Months

Change (value at 12 months minus value at baseline) in left ventricular end diastolic volume on cardiac magnetic resonance imaging

Outcome measures

Outcome measures
Measure	Eplerenone n=14 Participants Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=19 Participants Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Assessment of Cardiac Diastolic Function Via Cardiac Imaging	-13 mL Standard Deviation 28	10 mL Standard Deviation 26

Adverse Events

Eplerenone

Serious events: 1 serious events

Other events: 12 other events

Deaths: 1 deaths

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Eplerenone n=20 participants at risk Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=20 participants at risk Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Social circumstances Medical condition leading to death	5.0% 1/20 • 12 Months	0.00% 0/20 • 12 Months

Other adverse events

Other adverse events
Measure	Eplerenone n=20 participants at risk Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity	Placebo n=20 participants at risk Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity
Cardiac disorders Dizziness	20.0% 4/20 • 12 Months	0.00% 0/20 • 12 Months
Gastrointestinal disorders Gastrointestinal Symptoms	20.0% 4/20 • 12 Months	15.0% 3/20 • 12 Months
Skin and subcutaneous tissue disorders Rash	15.0% 3/20 • 12 Months	5.0% 1/20 • 12 Months
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	15.0% 3/20 • 12 Months	5.0% 1/20 • 12 Months
Infections and infestations Other Infection	25.0% 5/20 • 12 Months	30.0% 6/20 • 12 Months
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	15.0% 3/20 • 12 Months	20.0% 4/20 • 12 Months
Cardiac disorders Cardiovascular Symptoms	10.0% 2/20 • 12 Months	15.0% 3/20 • 12 Months
Injury, poisoning and procedural complications Injuries	10.0% 2/20 • 12 Months	15.0% 3/20 • 12 Months
Respiratory, thoracic and mediastinal disorders Other Respiratory Symptoms	5.0% 1/20 • 12 Months	10.0% 2/20 • 12 Months
Renal and urinary disorders Urinary Volume Increase	10.0% 2/20 • 12 Months	0.00% 0/20 • 12 Months
Surgical and medical procedures Underwent Non-Cardiac Elective Procedure	5.0% 1/20 • 12 Months	25.0% 5/20 • 12 Months

Additional Information

Dr. Steven K. Grinspoon

Massachusetts General Hospital

Phone: 617-724-9109

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place