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

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

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 Overview

• Status: Unknown
• Conditions: Heart Diseases; Anemia, Iron-Deficiency; Chronic Heart Failure
• Intervention / Treatment: Drug: Venofer (intravenous iron sucrose)

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

• Study Type: Interventional
• Enrollment: 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Darlington O Okonko, BSc, MRCP; Phone Number: 02073518700; Email: D.OKONKO@IC.AC.UK

Study Locations

• Poland
  • Wroclaw
    • Weigla 5, Wroclaw, Poland, 50981
      • Recruiting
      • 4th Military Clinical Hospital
      • Contact: Piotr Ponikowski, MD PHD; Phone Number: (48) 717660250; Email: piotrponikowski@hotmail.com
      • Principal Investigator: Piotr Ponikowski, MD PHD
• United Kingdom
  • Berkshire
    • Wexham Park, Slough, Berkshire, United Kingdom, SL2 4HL
      • Recruiting
      • Wexham Park Hospital
      • Contact: Constantinous Missouris, MD; Phone Number: (44)01753 634680; Email: cmissouris@btopenworld.com
      • Contact: Amit K Mandall, MRCP; Phone Number: (44)01753 634680; Email: akjm@mac.com
      • Principal Investigator: Constantinous Missouris, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 93 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Change in peak VO2 from baseline to week 18

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

• Sponsor: National Heart and Lung Institute
• Collaborators: Wexham Park Hospital; 4th Military Hospital
• Investigators: Principal Investigator: Philip A Poole-Wilson, MD,FRCP, NHLI, Imperial College School of Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Study Completion: February 1, 2006

Study Registration Dates

• First Submitted: August 1, 2005
• First Submitted That Met QC Criteria: August 1, 2005
• First Posted (Estimate): August 2, 2005

Study Record Updates

• Last Update Posted (Estimate): August 17, 2005
• Last Update Submitted That Met QC Criteria: August 16, 2005
• Last Verified: January 1, 2005

More Information

Terms related to this study

• Keywords: Iron Deficiency; ANAEMIA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Heart Failure; Heart Diseases; Anemia, Iron-Deficiency; Hematinics; Ferric Oxide, Saccharated
• Other Study ID Numbers: FERRIC-HF; FERRIC-Hef1; RD010; 131/03L