Clinical trial NCT00125996: Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure
Official 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Chronic Heart Failure
Heart Diseases
Anemia, Iron-Deficiency
Keywords: ANAEMIA
Iron Deficiency
Lead sponsor: National Heart and Lung Institute
Sponsor class: OTHER
Collaborators: name: Wexham Park Hospital
name: 4th Military Clinical Hospital with Polyclinic, Poland
First posted: 2005-08-02
Enrollment: 42
Sex: ALL
Minimum age (years): 30
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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

Eligibility criteria: 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

Primary outcomes:
measure: Change in peak VO2 from baseline to week 18
Secondary outcomes:
measure: Change in cardiopulmonary exercise duration from baseline to week 18
measure: 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
measure: Change in left ventricular (LV) systolic and diastolic dimensions, and function from baseline to week 18
measure: 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
measure: Change in haematological and biochemical indices (Hb, Hct, iron status, N-BNP, cytokines and oxidative stress) from baseline to week 18
measure: Number and incidence of adverse events
measure: Changes in liver function tests and renal function tests
measure: Changes in vital parameters
Other outcomes:
Locations:
city: Weigla 5
country: Poland
facility: 4th Military Clinical Hospital
state: Wroclaw
city: Wexham Park, Slough
country: United Kingdom
facility: Wexham Park Hospital
state: Berkshire
Study officials:
affiliation: NHLI, Imperial College School of Medicine
name: Philip A Poole-Wilson, MD,FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Roughton M, Foldes G, Thum T, Majda J, Banasiak W, Missouris CG, Poole-Wilson PA, Anker SD, Ponikowski P. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial. J Am Coll Cardiol. 2008 Jan 15;51(2):103-12. doi: 10.1016/j.jacc.2007.09.036.