A two-center, randomised, single-blind (physician), prospective, controlled study to assess the acute (8 weeks) and chronic (16 weeks) effects of intravenous Iron sucrose supplementation in anaemic and non-anaemic iron deficient patients with chronic heart failure

Hypotheses: (1)Treatment of anaemic and non-anaemic iron-deficient CHF patients with IV iron sucrose improves exercise capacity as measured by peak VO2. (2)IV iron sucrose is safe and well tolerated in subjects with moderate to severe CHF.

Condition	Intervention	Phase
Chronic Heart Failure Anaemia Iron Deficiency	Drug: Venofer (intravenous iron sucrose)	Phase I Phase II

Further Study Details: 

Primary Outcomes: Change in peak VO2 from baseline to week 18
Secondary Outcomes: 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
Expected Total Enrollment:  42

Study Phase & 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

Ages Eligible for Study:  30 Years   -   95 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• ≥21 years of age and have signed written informed consent
• Stable symptomatic CHF; NYHA III/IV and 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 g/l or 100-300 g/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 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00125996

Darlington O Okonko, BSc, MRCP      02073518700    D.OKONKO@IC.AC.UK

Poland, Wroclaw
      4th Military Clinical Hospital, Weigla 5,  Wroclaw,  50981,  Poland; Recruiting
United Kingdom, Berkshire
      Wexham Park Hospital, Wexham Park, Slough,  Berkshire,  SL2 4HL,  United Kingdom; Recruiting

Study chairs or principal investigators

Philip A Poole-Wilson, MD,FRCP,  Principal Investigator,  NHLI, Imperial College School of Medicine   

Study ID Numbers:  FERRIC-HF; FERRIC-Hef1; RD010; 131/03L
Last Updated:  August 1, 2005
Record first received:  August 1, 2005
ClinicalTrials.gov Identifier:  NCT00125996
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
ClinicalTrials.gov processed this record on 2005-08-02