Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure
Condition: Chronic Heart Failure
MeSH terms: Heart Failure
Intervention: Polysaccharide Iron Complex 150 mg; Placebo (for Polysaccharide Iron Complex)
Intervention description: Oral Iron; Sugar capsule designed to mimic Polysaccharide Iron Complex.
Intervention MeSH terms: Iron
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 225.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine if oral iron (Fe) polysaccharide is superior to
      oral placebo in improving functional capacity as measured by change in peak VO2 (oxygen
      uptake) by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with
      HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.

      Hypothesis: In a broad population of HFrEF patients with Fe deficiency, compared to oral
      placebo, therapy with oral Fe polysaccharide will be associated with improvement in
      functional capacity at 16 weeks as assessed by CPET.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age >18 years

          2. Previous clinical diagnosis of heart failure with current New York Heart Association
             (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 9.0-13.5 g/dL (males), 9-13.5 (females) at time of enrollment

          5. Stable 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

             a. 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 bicycle/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 Fe 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