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

Phase 1
Conditions
Chronic Heart Failure
Heart Diseases
Anemia, Iron-Deficiency
Registration Number
NCT00125996
Lead Sponsor
National Heart and Lung Institute
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

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
42
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Change in peak VO2 from baseline to week 18
Secondary Outcome Measures
NameTimeMethod
Change in cardiopulmonary exercise duration from baseline to 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 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

Trial Locations

Locations (2)

Wexham Park Hospital

🇬🇧

Wexham Park, Slough, Berkshire, United Kingdom

4th Military Clinical Hospital

🇵🇱

Weigla 5, Wroclaw, Poland

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