Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised Controlled Study to Assess the Acute and Chronic Effects of Intravenous Iron Supplementation in Anaemic and Non-Anaemic Iron Deficient Patients With Chronic Heart Failure
Brief Summary: This is a two-center, randomised, single-blind (physician), prospective, controlled study to assess the acute (8 weeks) and chronic (16 weeks) effects of intravenous (IV) iron sucrose supplementation in anaemic and non-anaemic iron deficient patients with chronic heart failure (CHF).

The hypotheses are:

* Treatment of anaemic and non-anaemic iron-deficient CHF patients with IV iron sucrose improves exercise capacity as measured by peak VO2.
* IV iron sucrose is safe and well tolerated in subjects with moderate to severe CHF.


Options:
A: Inclusion Criteria:

* Iron deficient subjects with stable chronic heart failure (CHF) (NYHA II-III) on optimal background therapy for CHF
* Reduced exercise capacity
* Reduced left ventricular ejection fraction
* 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
* No other significant cardiac or general disorder that would compromise participation in the study
B: Inclusion Criteria:

* Signed informed consent prior to study specific procedures.
* Premenopausal, regularly menstruating women.
* Age ≥18 years.
* Body weight between 50 and 90 kg.
* Haemoglobin ≥115 g/L.
* Iron deficiency at screening defined as follows:
* S-ferritin level \<50 ng/mL, AND, TfS \<20%, OR,
* S-ferritin level \<15 ng/mL.
* Serum C-reactive protein:
* \<5 mg/L if not on oral contraception, OR,
* \<20 mg/L if use of oral contraception.
* Minimum total score of 5 on the Piper Fatigue Scale (PFS) (mean of items 2 to 23).
* Negative pregnancy test (serum human chorionic gonadotropin (hCG) at screening.
* Normal levels of vitamin B12 and folic acid at screening.
* Adequate contraception during the study period and for 1 month following study completion.
* Availability and willingness to complete all study visits and procedures per protocol.

Exclusion Criteria:

* Haemoglobin level \<115 g/L.
* Haemoglobinopathy.
* Haemochromatose.
* Major depressive disorder based on Patient Health Questionnaire (PHQ-9) (5 items with scores ≥2; one of which corresponds to question number 1 or 2).
* Any active or unstable concurrent medical condition (e.g., cancer, renal dysfunction, liver dysfunction (aspartate aminotransferase (AST); alanine aminotransferase (ALT) \>3-fold upper limit), angina (Class IV).
* Known human immunodeficiency virus/acquired immunodeficiency syndrome, hepatitis B virus or hepatitis C virus infection.
* Chronic inflammatory disease (e.g., rheumatoid arthritis; inflammatory bowel disease).
* Documented history of clinically significant level of sleep apnoea defined as 5 or more episodes per hour of any type of apnoea.
* Intake of concurrent medications that could interfere with physical or mental performance (e.g., antidepressive, antihistamines, narcotic or any chemotherapeutic agents known to cause drowsiness).
* Important recent weight loss (\>10% within the past month).
* Body weight \<50 kg or \>90 kg.
* Thyroid dysfunction, thyroid stimulating hormone \>4 μU/mL.
* Intake of iron preparations 4 weeks prior to screening.
* Use of gestagens e.g., Implanon, Mirena, Depo-Provera for menstruation repression (see Section 7.7, Prohibited Therapy or Concomitant Treatment, page 35).
* Known hypersensitivity to FCM or to any other iron preparation.
* Pregnancy (positive hCG test at screening) or breast feeding.
* Participation in any other interventional trial within 4 weeks prior to screening.
* Inability to fully comprehend and/or perform study procedures or provide written consent in the Investigator's opinion.
* Subject is not using adequate contraceptive precautions during the study and for up to 1 month after the last dose of the study medication. A highly effective method of birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomised partner.
* Subject previously has entered this study.
* Subject will not be available for follow-up assessments.
C: 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
D: 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

Answer: C