Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Trial to Assess the Effects of Iron Supplementation in Heart Failure Patients With Anemia: The IRON-HF Study
Brief Summary: Anemia has been demonstrated to be a common finding in patients with heart failure (HF). Previous studies in hospitalized patients with HF have found a prevalence of anemia ranging from 15% to 63%. More importantly, anemic patients with HF have increased morbidity and mortality. The mechanisms underlying anemia in HF are multifactorial, involving mild to moderate forms of anemia of chronic disease and ferropenic anemia. The clinical impact of iron supplementation in HF patients who have a relatively preserved renal function and either chronic disease anemia, ferropenic anemia or both remains largely unknown. The route of iron administration that could be most clinically effective is also unclear. Thus, the primary aim of the IRON-HF study is to assess the effects of iron supplementation alone (IV or PO) on parameters of functional capacity in HF patients with anemia with decreased availability of iron.


Options:
A: Inclusion Criteria:

* ≥21 years of age and have signed written informed consent
* Stable symptomatic CHF; NYHA III/IV and left ventricular ejection fraction (LVEF) ≤40%, or if NYHA II then LVEF must be ≤35%, as assessed within last 6 months using echocardiographic or magnetic resonance imaging techniques.
* On optimal conventional therapy for at least 4 weeks prior to recruitment and without dose changes for at least 2 weeks.
* Peak VO2 ≤ 18 ml/kg/min on modified Naughton protocol cardiopulmonary exercise testing.
* Mean of the 2 screening Hb concentrations (week-2 and week-1) \< 12.5 g/dl (anaemic group, 50% of study population) or 12.5-14.0 g/dl (non-anaemic group, 50% of study population).
* Ferritin \<100 µg/l or 100-300 µg/l with TSAT \<20%.
* Normal red cell folate and vitamin B12 status (according to local lab reference range).
* Resting blood pressure ≤160/100 mmHg.

Exclusion Criteria:

* History of acquired iron overload; known haemochromatosis or first relatives with haemochromatosis; and allergic disorders (asthma, eczema, and anaphylactic reactions).
* Known hypersensitivity to parental iron preparations.
* Known active infection, bleeding, malignancy and haemolytic anaemia.
* History of chronic liver disease and/or alanine transaminase (ALT) or aspartate transaminase (AST) \>3 times the upper limit of the normal range; chronic lung disease; myelodysplastic disorder; and known HIV/AIDS disease.
* Recipient of immunosuppressive therapy or renal dialysis.
* History of erythropoietin, IV or oral iron therapy, and blood transfusion in previous 30 days.
* Unstable angina pectoris, as judged by the investigator; severe uncorrected valvular disease or left ventricular outflow obstruction; obstructive cardiomyopathy; uncontrolled fast atrial fibrillation or flutter (heart rate \>110 beats per minute \[bpm\]); uncontrolled symptomatic brady- or tachyarrhythmias.
* Musculoskeletal limitation that, in the judgement of the investigator, would impair cardiopulmonary exercise testing.
* Pregnant or breast-feeding
* Inability to comprehend study protocol
* Parallel participation in another clinical trial
B: Inclusion Criteria:

* 18 years of age or older;
* Outpatients followed at a HF Clinic in a tertiary care Hospital with clinical diagnosis of HF for at least 3 months before study entry;
* NYHA functional class II to IV, who are able to perform ergospirometry;
* Documentation of LVEF \< 40% within the last 6 months;
* Adequate baseline therapy for HF based on patient's functional class (β-blockers, ACE inhibitors irrespective of functional class except if contra-indications, digoxin, spironolactone if NYHA class III or IV);
* Stable baseline HF therapy with same doses of medications and no intent to increase doses for the following 3 months;
* Hemoglobin ≤ 12 g/dl and \> 9 g/dl;
* Transferrin saturation \< 20% and ferritin \< 500 µg/L;
* Ability to provide written informed consent.

Exclusion Criteria:

* Any clinically overt bleeding: gastrointestinal bleeding, hypermenorrhea, history of peptic ulcer without evidence of healing or inflammatory intestinal diseases;
* Uncorrected hypothyroidism;
* Other inflammatory, neoplastic or infectious disease;
* Serum creatinine \> 1,5 mg/dl;
* Previous intolerance to oral elemental iron compounds;
* HF due to alcoholic cardiomyopathy, current regular drinker of alcoholic beverages or HF due to peripartum cardiomyopathy;
* Recent admission for decompensated HF (last month)
* Recent myocardial revascularization procedures (last 3 months);
* Recent ACS, stroke or TIA (last 3 months);
* Active or metastatic neoplastic disease with life expectancy of less than a year;
* Patients in heart transplantation list;
* Patients that had participated in any other clinical trial or study within the last month;
* Pregnant or lactating women;
* Pre-menopausal women that are not using any effective method of contraception;
* Patients using prohibited medications or that have not yet accomplished the wash-out period;
* Patients currently participating in cardiovascular rehabilitation programs.
C: Inclusion Criteria:

* Iron deficient subjects with stable chronic heart failure (CHF) (NYHA II-III) on optimal background therapy for CHF
* Reduced left ventricular ejection fraction
* Capable of completing 6 minute walk test
* At least 18 years of age and with written informed consent prior to any study specific procedures

Exclusion Criteria:

* Erythropoietin stimulating agent (ESA) use, IV iron therapy and/or blood transfusion in previous 6 weeks prior to randomisation
* Exercise training program(s) in the 3 months prior to screening or planned in the next 6 months
* Chronic liver disease and/or elevated liver enzymes
* Vitamin B12 and/or serum folate deficiency
* Subject is not using adequate contraceptive precautions during the study
* Body weight ≤ 35 kg
* No other significant cardiac or general disorders that would compromise the ability to give informed consent and/or comply with study procedures
D: Inclusion Criteria:

* Age 18 to 100
* To be receiving intravenous iron

Exclusion Criteria:

* Age \< 18
* Hemodialysis
* Previous exposure to intravenous iron
* Unable to provide written consent

Answer: B