Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure

• Change in cardiopulmonary exercise duration from baseline to week 18
• Change in distance walked during 6 minute walk test from baseline to end of repletion phase in treatment group or week 8 in control group, and week 18
• Change in left ventricular (LV) systolic and diastolic dimensions, and function from baseline to week 18
• Change in symptom status (New York Heart Association [NYHA] class, Minnesota Living with Heart Failure Questionnaire [MLHFQ], visual analogue fatigue scale) from baseline to week 1,week 8, and week 18
• Change in haematological and biochemical indices (Hb, Hct, iron status, N-BNP, cytokines and oxidative stress) from baseline to week 18
• Number and incidence of adverse events
• Changes in liver function tests and renal function tests
• Changes in vital parameters

• Change in cardiopulmonary exercise duration from baseline to week 18
• Change in distance walked during 6 minute walk test from baseline to end of repletion phase in treatment group or week 8 in control group, and week 18
• Change in LV systolic and diastolic dimensions, and function from baseline to week 18
• Change in symptom status (NYHA class, MLHFQ, visual analogue fatigue scale) from baseline to week 1,week 8, and week 18
• Change in haematological and biochemical indices (Hb, Hct, iron status, N-BNP, cytokines and oxidative stress) from baseline to week 18.
• Number and incidence of adverse events; changes in liver function tests and renal function tests; changes in vital parameters

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.

Study Phase and Design:

Prospective two-centre, randomized, controlled, open-label, observer-blinded, parallel-group study

Primary Objective:

To evaluate the effect of intravenous (IV) iron supplementation on exercise tolerance, as determined by peak VO2.

Secondary Objectives:

• To evaluate the effects of IV iron supplementation on exercise duration, left ventricular (LV) structure and function, symptom status (NYHA class, Minnesota Living with Heart Failure Questionnaire [MLHFQ], and subjective fatigue score), and haematological and biochemical (haemoglobin [Hb], haematocrit [Hct], iron status, N-BNP, cytokines and oxidative stress) indices.
• To evaluate the safety profile of IV iron in subjects with moderate to severe CHF.

Sample Size:

42 subjects (28 IV iron, 14 placebo); 50% anaemic and 50% non-anaemic

• Chronic Heart Failure
• Heart Diseases
• Anemia, Iron-Deficiency

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

• Wexham Park Hospital
• 4th Military Hospital, Poland