Effects of Eplerenone on Cardiovascular Disease in HIV (MIRACLE HIV Study)
Mineralocorticoid Receptor Antagonism for Cardiovascular Health in HIV--The MIRACLE HIV Study
1 other identifier
interventional
40
1 country
1
Brief Summary
HIV-infected individuals treated with antiretroviral medications are living longer, but have an increased risk of heart disease when compared to non-HIV-infected individuals. A hormone called aldosterone, which regulates blood pressure and sodium balance, is elevated in the HIV population in association with with increased belly fat and altered glucose metabolism. Elevations in aldosterone hormone may also be associated with abnormal blood flow, inflammation, and coronary plaque in the heart. This study is being conducted to evaluate whether therapies to reduce the actions of aldosterone may decrease the burden and progression of heart disease in the HIV population.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable hiv
Started Jan 2017
Longer than P75 for not_applicable hiv
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 7, 2016
CompletedFirst Posted
Study publicly available on registry
April 15, 2016
CompletedStudy Start
First participant enrolled
January 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 17, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 17, 2022
CompletedResults Posted
Study results publicly available
June 2, 2023
CompletedJune 6, 2023
June 1, 2023
5.2 years
April 7, 2016
March 16, 2023
June 2, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Myocardial Perfusion by PET
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.
12 Months
Myocardial Perfusion by MRI
Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by myocardial blood flow measured via cardiac magnetic resonance imaging
12 Months
Myocardial Inflammation
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
12 Months
Secondary Outcomes (13)
Coronary Plaque
12 Months
Markers of Vascular Dysfunction
12 Months
Markers of Systemic Inflammation hsIL-6
12 Months
Markers of Systemic Inflammation hsCRP
12 Months
Markers of Immune Activation MCP-1
12 Months
- +8 more secondary outcomes
Study Arms (2)
Eplerenone
EXPERIMENTALEplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months
Placebo
PLACEBO COMPARATORPlacebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months
Interventions
Eligibility Criteria
You may qualify if:
- Ages 40-65 years
- Antiretroviral use (ART) \>12 months and HIV viral load \<100 copies/mL
- VAT\> 110cm2
You may not qualify if:
- Antihypertensive use including, ACE Inhibitor, ARB, MR blockade, diuretic, potassium (K) supplementation; or BP\>140/90 mmHg. Stable use (\>3 months) of beta-blockers or calcium channel blockers (CCB) (except verapamil) is allowed.
- Unstable statin use \<12 months. Stable use (\>12 months) is allowed.
- Use of full dose ritonavir, nelfinavir, clarithromycin, and other strong inhibitors of CYP3A4, as well as CYP3A4 inducers.
- Continuous oral steroid use (equivalent to prednisone \> 5 mg daily) within the last 3 months.
- Uncontrolled diabetes requiring insulin and/or HbA1c \> 7.5%.
- Creatinine (Cr) \> 1.5 mg/dL or estimated GFR\<60 mL/min/1.73m2.
- K \> 5.5 mEq/L.
- Hemoglobin \< 10 g/dL.
- Known liver disease or ALT \>3x ULN.
- History of congestive heart failure, stroke, myocardial infarction, or known coronary artery disease.
- Pregnant, actively seeking pregnancy or breastfeeding.
- Estrogen, progestin derivative, or other sex steroid use within last 3 months. Stable physiologic testosterone replacement (\> 3 months) is acceptable.
- Current bacterial or other infections.
- Active substance abuse.
- Significant radiation exposure over the course of the year prior to randomization (e.g., radiation therapy, PCI, catheter ablation of arrhythmia) within 12 months of randomization.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Related Publications (6)
Srinivasa S, Fitch KV, Wong K, Torriani M, Mayhew C, Stanley T, Lo J, Adler GK, Grinspoon SK. RAAS Activation Is Associated With Visceral Adiposity and Insulin Resistance Among HIV-infected Patients. J Clin Endocrinol Metab. 2015 Aug;100(8):2873-82. doi: 10.1210/jc.2015-1461. Epub 2015 Jun 18.
PMID: 26086328BACKGROUNDWalpert AR, Gupta M, Dunderdale CN, Haptu HH, Manandhar M, deFilippi CR, Burdo TH, Lee H, Kwong RY, Srinivasa S. Exploring the PREVENT HF score and myocardial function among persons with HIV. AIDS. 2025 Sep 1;39(11):1592-1597. doi: 10.1097/QAD.0000000000004252. Epub 2025 Jun 4.
PMID: 40478895DERIVEDSrinivasa S, Walpert AR, Huck D, Thomas TS, Dunderdale CN, Lee H, Dicarli MF, Adler GK, Grinspoon SK. Coronary Microvascular Dysfunction Is Present Among Well-Treated Asymptomatic Persons With HIV and Similar to Those With Diabetes. Open Forum Infect Dis. 2024 Apr 26;11(5):ofae234. doi: 10.1093/ofid/ofae234. eCollection 2024 May.
PMID: 38813261DERIVEDSrinivasa S, Abohashem S, Walpert AR, Dunderdale CN, Iyengar S, Shen G, Jerosch-Herold M, deFilippi CR, Robbins GK, Lee H, Kwong RY, Adler GK, Tawakol A, Grinspoon SK. Mineralocorticoid Receptor Antagonism by Eplerenone and Arterial Inflammation in HIV: The MIRABELLA HIV Study. JAMA Cardiol. 2024 Feb 1;9(2):189-194. doi: 10.1001/jamacardio.2023.4578.
PMID: 38090987DERIVEDThomas TS, Dunderdale C, Lu MT, Walpert AR, Shen G, Young MCH, Torriani M, Chu JT, Haptu HH, Manandhar M, Wurcel A, Adler GK, Grinspoon SK, Srinivasa S. Visceral Adiposity Index as a Measure of Cardiovascular Disease in Persons With Human Immunodeficiency Virus. Open Forum Infect Dis. 2023 Jul 24;10(8):ofad398. doi: 10.1093/ofid/ofad398. eCollection 2023 Aug.
PMID: 37559752DERIVEDSrinivasa S, Walpert AR, Thomas TS, Huck DM, Jerosch-Herold M, Islam S, Lu MT, Burdo TH, deFilippi CR, Dunderdale CN, Feldpausch M, Iyengar S, Shen G, Baak S, Torriani M, Robbins GK, Lee H, Kwong R, DiCarli M, Adler GK, Grinspoon SK. Randomized Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Myocardial Perfusion and Function Among Persons With Human Immunodeficiency Virus (HIV)-Results From the MIRACLE HIV Study. Clin Infect Dis. 2023 Oct 13;77(8):1166-1175. doi: 10.1093/cid/ciad310.
PMID: 37243345DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Steven K. Grinspoon
- Organization
- Massachusetts General Hospital
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- not applicable
- 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
- Professor of Medicine
Study Record Dates
First Submitted
April 7, 2016
First Posted
April 15, 2016
Study Start
January 1, 2017
Primary Completion
March 17, 2022
Study Completion
March 17, 2022
Last Updated
June 6, 2023
Results First Posted
June 2, 2023
Record last verified: 2023-06