Table 3.

IRONOUT HF Inclusion and Exclusion Criteria

Inclusion Criteria
1. Age ≥18 years
2. Previous clinical diagnosis of heart failure with current NYHA Class II-IV symptoms, LVEF≤0.40
within 2 years prior to consent, and ≥3 months after a major change in cardiac status (i.e. CABG or
CRT).
3. Serum ferritin between 15–100 ng/ml or serum ferritin between 100–299 ng/ml with transferrin
saturation <20%
4. Hemoglobin 9.0–15.0 g/dL (males), 9.0–13.5 (females) at time of enrollment
5. Evidence-based medical therapy for HF (including beta-blocker and ACE-inhibitor/ARB unless
previously deemed intolerant and diuretics as necessary) with ≤100% change in dose for 30 days
prior to randomization. Changes in diuretic dose guided by a patient-directed flexible dosing
program are considered stable medical therapy
6. Willingness to provide informed consent

Exclusion Criteria
1. Presence of a neuromuscular, orthopedic or other non-cardiac condition that prevents the patient
from exercise testing on a cycle/treadmill ergometer and/or inability to achieve an RER ≥ 1.0 on
screening/baseline CPET
2. Severe renal dysfunction (eGFR< 20 ml/min/1.73m²)
3. Severe liver disease (ALT or AST > 3x normal, alkaline phosphatase or bilirubin >2x normal)
4. Gastrointestinal conditions known to impair Fe absorption (i.e. inflammatory bowel disease)
5. Known active infection as defined by current use of oral or intravenous antimicrobial agents
6. Documented active gastrointestinal bleeding
7. Active malignancy other than non-melanoma skin cancers
8. Anemia with known cause other than Iron deficiency or chronic disease
9. Fe overload disorders (i.e. hemochromatosis or hemosiderosis)
10. History of erythropoietin, IV or oral Fe therapy, or blood transfusion in previous 3 months.
11. Current ventricular assist device
12. Anticipated cardiac transplantation within the next 4 months
13. Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive
pericarditis or tamponade
14. Previous adverse reaction to study drug or other oral Fe preparation
15. Known or anticipated pregnancy in the next 4 months