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Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure (ATHENA-HF)

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ClinicalTrials.gov Identifier: NCT02235077
Recruitment Status : Completed
First Posted : September 9, 2014
Results First Posted : May 17, 2017
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Duke University

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.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Spironolactone Drug: Placebo Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy - HF (ATHENA-HF)
Actual Study Start Date : December 30, 2014
Actual Primary Completion Date : April 12, 2016
Actual Study Completion Date : June 6, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Spironolactone
Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours
Drug: Spironolactone

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.

Other Name: aldactone

Placebo Comparator: Placebo
Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours
Drug: Placebo

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.





Primary Outcome Measures :
  1. 96 Hour Change in NT-proBNP [ Time Frame: Randomization to 96 hours ]
    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.


Secondary Outcome Measures :
  1. 96 Hour Change in Clinical Congestion Score [ Time Frame: Randomization through 96 hours ]
    Clinical congestion score will be assessed at randomization, 96 hours, and at discharge. Scale consisted of sum of six signs and symptoms of congestion, each scored 0-3. Zero indicates no sign/symptom and 3 indicates worst case of sign/symptom. Score range 0-18 with 18 being worst score.

  2. 96 Hour Change in Dyspnea Likert Score [ Time Frame: Randomization through 96 hours ]
    Dyspnea relief via 7-point Likert scale will be assessed at randomization, 96 hours, and at discharge. The Likert score was defined as 1=markedly improved, 2=moderately improved, 3=minimally improved; 4=no change, 5=minimally worse, 6=moderately worse, and 7=markedly worse as compared with the degree of dyspnea present at randomization.

  3. 96 Hour Change in Serum Creatinine [ Time Frame: Randomization through 96 hours ]
    Renal function via serum creatinine, will be assessed at randomization and daily through 96 hours

  4. 96 Hour Net Fluid Output [ Time Frame: Randomization through 96 hours ]
    Fluid intake and urine output will be assessed daily while in hospital through 96 hours. Net fluid output (output minus input) through 96 hours is reported.

  5. 96 Hour Change in Body Weight [ Time Frame: Randomization through 96 hours or earlier discharge ]
    Baseline body weight assessment will be completed, and changes in weight documented daily through 96 hours or earlier discharge

  6. 96 Hour Change in Serum Potassium Levels [ Time Frame: Baseline, 96 hours ]
    Change in serum potassium levels at 96 hours as compared to baseline.

  7. Change in Loop Diuretics Requirements From Baseline to 30 Days [ Time Frame: Randomization through Day 30 ]
    Medications will be reviewed to assess loop diuretic dose requirements through Day 30 following randomization

  8. Presence of Outpatient Worsening Heart Failure Symptoms Through Day 30 [ Time Frame: Hospital discharge through Day 30 ]
    Outpatient worsening heart failure symptoms will be assessed from discharge through Day 30

  9. 96 Hour Change in Dyspnea Visual Analog Scale [ Time Frame: Randomization to 96 hours ]
    Dyspnea visual analog scale change from randomization to 96 hours. Scale range 0-100 with 100 being the best possible score.


Other Outcome Measures:
  1. Day 60 Mortality [ Time Frame: 60 days post randomization ]
    All participants will be contacted by telephone at 60 days, +/- 3 days post randomization to assess vital status (death).



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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Taking eplerenone or >25 mg spironolactone at baseline
  • eGFR < 30 ml/min/1.73m2
  • Serum K+ >5.0 mmol/L. If a repeat measurement within the enrollment window is <5.0, the patient can be considered for inclusion.
  • 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
  • Enrollment in another randomized clinical trial during index hospitalization

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02235077


Locations
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Boston VA Healtcare System
West Roxbury, Massachusetts, United States, 02132
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
Saint Louis University Hospital
Saint Louis, Missouri, United States, 63117
United States, New York
Stony Brook University Medical Center
Stony Brook, New York, United States, 11794
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
Southeastern Regional Medical Center
Lumberton, North Carolina, United States, 28358
United States, Ohio
University Hospitals - Case Medical Center
Cleveland, Ohio, United States, 44106
Metro Health System
Cleveland, Ohio, United States, 44109
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Lancaster General Hospital
Lancaster, Pennsylvania, United States, 17603
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Jefferson Medical College
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Michael Debakey VA Medical Center
Houston, Texas, United States, 77030
United States, Utah
University of Utah School of Medicine
Salt Lake City, Utah, United States, 84132
Utah VA Medical Center
Salt Lake City, Utah, United States, 84132
United States, Vermont
The University of Vermont- Fletcher Allen Health Care
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Duke University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Adrian Hernandez, MD Duke University Health Systems
Study Chair: Eugene Braunwald, MD Harvard University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02235077     History of Changes
Other Study ID Numbers: Pro00057090
5U01HL084904 ( U.S. NIH Grant/Contract )
First Posted: September 9, 2014    Key Record Dates
Results First Posted: May 17, 2017
Last Update Posted: June 14, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Duke University:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Spironolactone
Aldactone

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents