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

Primary Purpose

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

Status
Unknown status
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Venofer (intravenous iron sucrose)
Sponsored by
National Heart and Lung Institute
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Heart Failure focused on measuring ANAEMIA, Iron Deficiency

Eligibility Criteria

30 Years - 95 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • 4th Military Clinical HospitalRecruiting
  • Wexham Park HospitalRecruiting

Outcomes

Primary Outcome Measures

Change in peak VO2 from baseline to week 18

Secondary Outcome Measures

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

Full Information

First Posted
August 1, 2005
Last Updated
August 16, 2005
Sponsor
National Heart and Lung Institute
Collaborators
Wexham Park Hospital, 4th Military Clinical Hospital with Polyclinic, Poland
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1. Study Identification

Unique Protocol Identification Number
NCT00125996
Brief Title
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

2. Study Status

Record Verification Date
January 2005
Overall Recruitment Status
Unknown status
Study Start Date
July 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 2006 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Heart and Lung Institute
Collaborators
Wexham Park Hospital, 4th Military Clinical Hospital with Polyclinic, Poland

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Heart Failure, Heart Diseases, Anemia, Iron-Deficiency
Keywords
ANAEMIA, Iron Deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Single
Allocation
Randomized
Enrollment
42 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Venofer (intravenous iron sucrose)
Primary Outcome Measure Information:
Title
Change in peak VO2 from baseline to week 18
Secondary Outcome Measure Information:
Title
Change in cardiopulmonary exercise duration from baseline to week 18
Title
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
Title
Change in left ventricular (LV) systolic and diastolic dimensions, and function from baseline to week 18
Title
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
Title
Change in haematological and biochemical indices (Hb, Hct, iron status, N-BNP, cytokines and oxidative stress) from baseline to week 18
Title
Number and incidence of adverse events
Title
Changes in liver function tests and renal function tests
Title
Changes in vital parameters

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Darlington O Okonko, BSc, MRCP
Phone
02073518700
Email
D.OKONKO@IC.AC.UK
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philip A Poole-Wilson, MD,FRCP
Organizational Affiliation
NHLI, Imperial College School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
4th Military Clinical Hospital
City
Weigla 5
State/Province
Wroclaw
ZIP/Postal Code
50981
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Piotr Ponikowski, MD PHD
Phone
(48) 717660250
Email
piotrponikowski@hotmail.com
First Name & Middle Initial & Last Name & Degree
Piotr Ponikowski, MD PHD
Facility Name
Wexham Park Hospital
City
Wexham Park, Slough
State/Province
Berkshire
ZIP/Postal Code
SL2 4HL
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Constantinous Missouris, MD
Phone
(44)01753 634680
Email
cmissouris@btopenworld.com
First Name & Middle Initial & Last Name & Degree
Amit K Mandall, MRCP
Phone
(44)01753 634680
Email
akjm@mac.com
First Name & Middle Initial & Last Name & Degree
Constantinous Missouris, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
18191732
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.
Results Reference
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Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure

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