Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure
ATHENA-HF
Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy - HF (ATHENA-HF)
2 other identifiers
interventional
360
1 country
22
Brief Summary
The primary objective of this study is to test the hypothesis that high-dose spironolactone will lead to greater proportional reduction in NT-proBNP levels from randomization to 96 hours over standard of care.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 heart-failure
Started Dec 2014
22 active sites
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
September 3, 2014
CompletedFirst Posted
Study publicly available on registry
September 9, 2014
CompletedStudy Start
First participant enrolled
December 30, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 12, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
June 6, 2016
CompletedResults Posted
Study results publicly available
May 17, 2017
CompletedJune 14, 2017
May 1, 2017
1.3 years
September 3, 2014
April 7, 2017
May 22, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
96 Hour Change in NT-proBNP
The Core Laboratory at Vermont will determine NT-proBNP levels for calculation of the endpoint from samples obtained at randomization and 96 hours respectively. NT-proBNP was converted to log scale.
Randomization to 96 hours
Secondary Outcomes (9)
96 Hour Change in Clinical Congestion Score
Randomization through 96 hours
96 Hour Change in Dyspnea Likert Score
Randomization through 96 hours
96 Hour Change in Serum Creatinine
Randomization through 96 hours
96 Hour Net Fluid Output
Randomization through 96 hours
96 Hour Change in Body Weight
Randomization through 96 hours or earlier discharge
- +4 more secondary outcomes
Other Outcomes (1)
Day 60 Mortality
60 days post randomization
Study Arms (2)
Spironolactone
ACTIVE COMPARATORSpironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours
Placebo
PLACEBO COMPARATORPlacebo 25mg or 100mg orally, once daily while in the hospital for 96 hours
Interventions
Patients receiving no MRA at home will receive spironolactone 100 mg (4x25 mg capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will be randomized to receive spironolactone 25 mg (1x25 mg capsules) or 100 mg (4x25 mg capsules) in hospital for 96 hours. The patients who are randomized to 25 mg spironolactone will also receive 75 mg placebo (3x25 mg capsules) in order to maintain blinding.
Patients receiving no MRA at home will receive 100 mg placebo (4x25 mg capsules) once daily for 96 hours. Patients who are randomized to 25 mg spironolactone will also receive 75 mg placebo (3x25 mg capsules) in order to maintain blinding.
Eligibility Criteria
You may qualify if:
- Male or female patient ≥21 years old
- Admitted to hospital for AHF with at least 1 symptom (dyspnea, orthopnea, or fatigue) and 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography) of congestion
- Patient must be randomized within 24 hours of first IV diuretic dose administered for the current episode of decompensation (regardless of where the diuretic was given e.g. office, ED, ambulance, hospital etc.)
- Estimated GFR of ≥30 mL/min/1.73m2 determined by the MDRD equation
- Serum K+ ≤5.0 mmol/L at enrollment
- NT-proBNP ≥1000 pg/mL or BNP ≥250 pg/mL, measured within 24h from randomization
- Not on MRA or on low-dose spironolactone (12.5 mg or 25 mg daily) at baseline
You may not qualify if:
- Taking eplerenone or \>25 mg spironolactone at baseline
- eGFR \< 30 ml/min/1.73m2
- Systolic blood pressure \<90 mmHg
- Hemodynamically significant arrhythmias or defibrillator shock within 1 week
- Acute coronary syndrome currently suspected or within the past 4 weeks
- Severe liver disease (ALT or AST \>3 x normal, alkaline phosphatase or bilirubin \>2x normal)
- Active infection (current use of oral or IV antimicrobial agents)
- Active gastrointestinal bleeding
- Active malignancy other than non-melanoma skin cancers
- Current or planned mechanical circulatory support within 30 days
- Post cardiac transplant or listed for transplant and expected to receive one within 30 days
- Current inotrope use
- Complex congenital heart disease
- Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade
- Previous adverse reaction to MRAs
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Duke Universitylead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
Study Sites (22)
Emory University School of Medicine
Atlanta, Georgia, 30322, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Boston VA Healtcare System
West Roxbury, Massachusetts, 02132, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Washington University
St Louis, Missouri, 63110, United States
Saint Louis University Hospital
St Louis, Missouri, 63117, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Duke University
Durham, North Carolina, 27705, United States
Southeastern Regional Medical Center
Lumberton, North Carolina, 28358, United States
University Hospitals - Case Medical Center
Cleveland, Ohio, 44106, United States
Metro Health System
Cleveland, Ohio, 44109, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Lancaster General Hospital
Lancaster, Pennsylvania, 17603, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Jefferson Medical College
Philadelphia, Pennsylvania, 19107, United States
Michael Debakey VA Medical Center
Houston, Texas, 77030, United States
University of Utah School of Medicine
Salt Lake City, Utah, 84132, United States
Utah VA Medical Center
Salt Lake City, Utah, 84132, United States
The University of Vermont- Fletcher Allen Health Care
Burlington, Vermont, 05401, United States
Related Publications (4)
Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.
PMID: 33107592DERIVEDGreene SJ, Felker GM, Giczewska A, Kalogeropoulos AP, Ambrosy AP, Chakraborty H, DeVore AD, Fudim M, McNulty SE, Mentz RJ, Vaduganathan M, Hernandez AF, Butler J. Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial. Can J Cardiol. 2019 Sep;35(9):1097-1105. doi: 10.1016/j.cjca.2019.01.022. Epub 2019 Feb 7.
PMID: 31230825DERIVEDButler J, Anstrom KJ, Felker GM, Givertz MM, Kalogeropoulos AP, Konstam MA, Mann DL, Margulies KB, McNulty SE, Mentz RJ, Redfield MM, Tang WHW, Whellan DJ, Shah M, Desvigne-Nickens P, Hernandez AF, Braunwald E; National Heart Lung and Blood Institute Heart Failure Clinical Research Network. Efficacy and Safety of Spironolactone in Acute Heart Failure: The ATHENA-HF Randomized Clinical Trial. JAMA Cardiol. 2017 Sep 1;2(9):950-958. doi: 10.1001/jamacardio.2017.2198.
PMID: 28700781DERIVEDButler J, Hernandez AF, Anstrom KJ, Kalogeropoulos A, Redfield MM, Konstam MA, Tang WH, Felker GM, Shah MR, Braunwald E. Rationale and Design of the ATHENA-HF Trial: Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure. JACC Heart Fail. 2016 Sep;4(9):726-35. doi: 10.1016/j.jchf.2016.06.003. Epub 2016 Aug 10.
PMID: 27522631DERIVED
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adrian Hernandez, MD
- Organization
- Duke Clinical Research Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Adrian Hernandez, MD
Duke University Health Systems
- STUDY CHAIR
Eugene Braunwald, MD
Harvard University
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 3, 2014
First Posted
September 9, 2014
Study Start
December 30, 2014
Primary Completion
April 12, 2016
Study Completion
June 6, 2016
Last Updated
June 14, 2017
Results First Posted
May 17, 2017
Record last verified: 2017-05
Data Sharing
- IPD Sharing
- Will not share