Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction

About the Study

Currently Recruiting: Participants

Study Drug/Intervention: Spirnolactone or eplerepnone

Anticipated Sample Size: 650 in the U.S. but may stop at 450

Study Timeline: This study is expected to conclude in December 2023.

ClinicalTrials.gov ID: NCT02901184



A 1:1 randomized, interventional, multicenter, safety/efficacy, parallel assignment, open-label treatment study conducted in the US and Sweden.

  • Intervention arm: Treatment with spironolactone/ eplerenone combined with usual care.
  • Control arm: Usual care alone.


Study Objectives

To conduct a registry-based randomized clinical trial (RRCT) to assess whether the initiation of spironolactone or eplerenone plus standard care compared to standard care alone improves outcomes in patients with heart failure with preserved ejection fraction (HFpEF).

Inclusion & Exclusion Criteria

Inclusion Criteria:

  1. Written informed consent
  2. Age >50 years
  3. Stable heart failure defined by symptoms and signs of heart failure as judged by local investigator. Patients may be enrolled as an outpatient or in-hospital at, or close to, the time of hospital discharge.
  4. Most recent left ventricular ejection fraction (LVEF) >40%
  5. Elevated natriuretic peptide levels, as defined by any of the following:
    1. most recent NT-proBNP >300 ng/L (or BNP>100 pg/mL) in sinus rhythm at the time of blood sampling; adjustments may be made for BMI according to table 3.
    2. most recent NT-proBNP >750 ng/L (or BNP >250 pg/mL) in atrial fibrillation at the time of blood sampling; adjustments may be made for BMI according to table 3.
    3. NT-proBNP >1200 ng/L (or BNP >400 pg/mL) within the last 12 months even if most recent value is lower.
  6. Regular use of loop diuretics, defined as daily or most days of the week
  7. NYHA Class II-IV


Exclusion Criteria:

  1. Previously enrolled in this study
  2. Known EF <40% ever
  3. Current absolute indication or contraindication for MRA in the judgment of the investigator. In the absence of absolute indication, patients currently treated with an MRA may have the MRA discontinued and then be included in the trial, according to investigator’s judgment
  4. Known chronic liver disease
  5. Probable alternative explanations for symptoms such as:
    1. Known primary cardiomyopathy that is hypertrophic with obstruction, constrictive, restrictive, infiltrative, or congenital (hypertrophic without current obstruction and other primary cardiomyopathies are allowed)
    2. Primary valve disease (to exclude a patient, the valve disease must be primary AND the primary cause of the symptoms)
    3. Significant chronic pulmonary disease defined by requirement for home O2
    4. Symptomatic anemia, defined as hemoglobin <10 g/dL (100 g/L) and this is the likely cause of the symptoms
    5. Right-sided HF not due to left-sided HF
  6. Heart transplant or LVAD recipient
  7. Presence of cardiac resynchronization therapy (CRT) device
  8. Systolic blood pressure <90 or >160 mm Hg at screening
  9. K >5.0 mmol/L (non-hemolysis sample*; most recent, not older than 30 days)
  10. eGFR by MDRD <30 ml/min/1.73m2 (most recent, not older than 30 days)
  11. Current dialysis
  12. Current lithium use
  13. Actual or potential for pregnancy
  14. Participation in another interventional clinical trial where a mineralocorticoid receptor antagonist is studied. Co-enrollment in trials and observational studies of other medical and device interventions is permitted
  15. Not suitable in the opinion of the Investigator due to severe or terminal comorbidity with poor prognosis, or characteristics that may interfere with adherence to trial protocol

*All K values in the trial refer to non-hemolysis samples. If hemolysis, blood test needs to be repeated.

Study Timeline

Duration of Study Participation

12 months at their site, then every 6 month contact for follow-up for up to 6 years


Study Follow-Up

After 12 months on study, patients are contacted via the DCRI Call Center every 6 months.

Additional Information

Current Sites

  • University of Texas Health and Science Center, San Antonio, TX
  • University of Cincinnati, Cincinnati, OH
  • University of Michigan, Ann Arbor, MI
  • Stern Cardiovascular, Germantown, TN
  • VA Medical Center, Memphis, TN
  • Ochsner Clinic, New Orleans, LA
  • Franciscan Health, Indianapolis, IN
  • Duke Health, Durham, NC
  • Northwell Health, Manhasset, NY

Sponsor/Funding Support

  • Sponsor: Uppsala Clinical Research Center (UCR), Uppsala University Hospital, Uppsala, Sweden
  • Funding: NHLBI; The Swedish Heart-Lung Foundation (Grant numbers 20150063, 20160562); The Swedish Research Council (Grant number 2017-00521); The Erling Persson Family Foundation (Grant number 20160928)

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