Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: Spironolactone; Placebo
Intervention description: 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.
Intervention MeSH terms: Spironolactone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 360.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Heart Failure; Heart Diseases; Cardiovascular Diseases; Spironolactone; Aldactone

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.
    

Eligibility 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