Condition category
Circulatory System
Date applied
28/11/2016
Date assigned
15/12/2016
Last edited
04/01/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Chronic heart failure (CHF) is a long-term condition where the heart has become weakened and isn’t able to pump blood around the body effectively. Chronic heart failure (CHF) is a very common problem. Despite improvements in treatment, many patients suffer limiting symptoms of shortness of breath and fatigue (extreme tiredness). Many patients with CHF have iron deficiency, meaning that the iron levels in their blood are too low or they are unable to utilise iron properly. This is associated with poor health outcomes, as iron is vital for the transport of oxygen around the body by red blood cells. The aim of this study is to find out whether treating iron-deficient CHF patients with intravenous (through a vein) iron is an effective way of reducing death due to circulatory system problems, and hospitalisation due to heart failure.

Who can participate?
Adults with chronic heart failure and iron deficiency.

What does the study involve?
Participants are randomly allocated to one of two groups. On the formal study visit, those in the first group receive iron through a trip at an individual dosage calculated from their height, weight and current iron levels. This takes around 15-30 minutes and participants need to stay in the clinic for around 30 minutes before going home. The whole visit takes between 1.5-2 hours. Those in the second group do not receive any iron and have blood tests at the formal study visit only. This takes between 1-1.5 hours. For those in both groups, subsequent study visits are arranged at 4 weeks and then three times a year for the rest of the study (between 2.5 and 4.5 years). At these follow up visits, participants undergo a clinical assessment (including checking weight, blood pressure and pulse) and are asked about their symptoms, medication and any medical problems since the last visit as well as completing a quality of life questionnaire.

What are the possible benefits and risks of participating?
If the iron treatment is successful and iron deficiency improves or is completely resolved, participants may feel better. There is no guarantee that a benefit will be felt by participants however. Nevertheless, results from this study may provide information which will help us to treat heart failure patients with iron deficiency more successfully in the future. Participants may experience side effects related to the iron therapy but these are rare. Initial screening tests may reveal a medical problem which may mean the participant can’t be entered into the study. Blood sampling is a part of this study and may cause minor discomfort and bruising.

Where is the study run from?
Queen Alexandra Hospital (lead site) and around 64 other NHS hospitals (UK)

When is the study starting and how long is it expected to run for?
August 2016 to February 2021

Who is funding the study?
1. British Heart Foundation (UK)
2. Pharmacosmos UK Ltd. (UK)

Who is the main contact?
Ms Elizabeth Thomson
elizabeth.thomson@glasgow.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Ms Elizabeth Thomson

ORCID ID

Contact details

Institute of Health and Wellbeing
College of Medical
Veterinary and Life Sciences
Robertson Centre for Biostatistics
University of Glasgow
Boyd Orr Building
Level 11
Glasgow
G12 8QQ
United Kingdom
+44 (0)141 330 4744
elizabeth.thomson@glasgow.ac.uk

Additional identifiers

EudraCT number

2015-004196-73

ClinicalTrials.gov number

NCT02642562

Protocol/serial number

31982

Study information

Scientific title

Effectiveness of intravenous iron treatment vs standard care in patients with heart failure and iron deficiency: a randomised, open-label multicentre trial (IRONMAN)

Acronym

IRONMAN

Study hypothesis

The aim of this study is to establish in patients with chronic heart failure and iron deficiency whether treatment with intravenous iron is effective in reducing death due to cardiovascular problems, and hospitalisation due to heart failure.

Ethics approval

East Midlands - Leicester South Research Ethics Committee, 25/02/2016, ref: 15/EM/0551

Study design

Randomised; Interventional; Design type: Not Specified, Not Specified

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cardiovascular disease, Primary sub-specialty: Other; UKCRC code/ Disease: Cardiovascular/ Other and unspecified disorders of the circulatory system

Intervention

Participants are randomised to one of two groups. All participants will be involved in the study for an average of 3 years (event driven trial, expected maximum 4.5 years, minimum 2.5 years – anticipated 2 years recruitment and a projected further 2 years of treatments/assessments, and a further closeout visit giving a range of projected patient participation of 2.5 – 4.5 years). All participants will be seen at 4 weeks and then every 4 months for study duration.

Intervention arm: Participants will receive an injection at the first formal study visit. The iron (iron isomaltoside 1000) is given intravenously as an infusion over 15-30 minutes and the dosage that is required is calculated according to participant weight and blood tests (calculated by electronic case record form, eCRF). The participant will then need to stay in the clinic for another 30 minutes before going home. This whole visit will take around 1.5 to 2 hours. Subsequent study visits will be arranged at around 4 weeks and then every 4 months (that is three times a year) until the study finishes. Blood will be tested at, or before, each study visit. At each visit there will be a clinical assessment (including checking weight, blood pressure, pulse) and the research team will ask about symptoms, medication and any medical problems since the last visit. A quality of life questionnaire will be completed (a second questionnaire and a walking test for 6 minutes will be offered at two further time points during the study). Each visit will last around 1 hour.
An iron infusion will only be required if iron levels are found to be low; on average we expect this to be around once a year (this will vary between participants – some needing it more often and others less often). The iron injection (Monofer®) will normally be given at a separate appointment although it may sometimes be possible for this to be given on the same day as the study visit. It is anticipated that participants will be in the clinic for around 1.5 to 2 hours for each iron injection.

Standard arm: Participants will not receive the intervention (intravenous iron). Blood will be tested at the formal study visit. This visit will take approximately 1 – 1.5 hours. Subsequent study visits will be arranged at convenient times at around 4 weeks and then every 4 months (that is three times a year) until the study finishes. Blood will be tested at, or before, each study visit. At each visit there will be a clinical assessment (including checking weight, blood pressure, pulse) and the research team will ask about symptoms, medication and any medical problems since the last visit. A quality of life questionnaire will be completed (a second questionnaire and a walking test for 6 minutes will be offered at two further time points during the study). Each visit will last around 1 hour.

Intervention type

Other

Phase

Phase IV

Drug names

Primary outcome measures

Cardiovascular CV mortality or hospitalisation for worsening heart failure is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average).

Secondary outcome measures

1. CV mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)
2. Hospitalisation for worsening heart failure (analysis will include first and recurrent hospitalisations) and is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)
3. All-cause mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)
4. CV mortality or first hospitalisation for major CV event (stroke, myocardial infarction [MI], heart failure). Days dead or hospitalised is assessed through review of case notes and reporting of patient, relative, carer or clinician at 2.5 years of follow up.
5. Physical domain of Quality of Life (QoL) - this will be the difference between groups at 4 months and also at 20 months. Minnesota Living with Heart Failure and EQ-5D are used at these time points to measure QoL.
6. Overall QoL assessment - this will be the difference between groups at 4 months and also at 20 months Minnesota Living with Heart Failure and EQ-5D are used at these time points to measure QoL.
7. Combined all-cause mortality or first all-cause unplanned hospitalization is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)
8. Days dead or hospitalised at 2.5 years (minimum duration of follow-up) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)
9. Quality-adjusted days alive and out of hospital at 2.5 years ) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)
10. CV hospitalisation (first event) ) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)
11. All-cause hospitalisation (first event) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)
12. Death due to sepsis is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)
13. Hospitalisation primarily for infection is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average)

Overall trial start date

08/07/2015

Overall trial end date

28/02/2021

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age ≥18 years
2. LVEF <45% within the last 6 months using any conventional imaging modality
3. New York Heart Association (NYHA) class II – IV
4. Iron deficient defined as a TSAT<20% and/or ferritin >100ug/L
5. Evidence of being in a higher risk heart failure group:
5.1. Current (with intention to discharge in next 48 hours) or recent (within 6 months) hospitalisation for heart failure, or
5.2. Outpatients with NTproBNP >250 ng/L in sinus rhythm or >1,000 ng/L in atrial fibrillation (or BNP of > 75 pg/mL or 300 pg/mL, respectively)
6. Able and willing to provide informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 1300; UK Sample Size: 1300

Participant exclusion criteria

1. Haematological criteria: ferritin >400ug/L; haemoglobin <9.0 or >13 g/dL in women or >14g/dL in men; (B12 or folate deficiency should be corrected but do not exclude the patient)
2. MDRD estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2
3. Chronic defined need for IV iron therapy
4. Likely to need or already receiving erythropoiesis stimulating agents (ESA)
5. Planned cardiac surgery or revascularisation or cardiac device implantation; within 3 months of a primary diagnosis of type 1 myocardial infarction (excluding small troponin elevations in the context of heart failure admissions), cerebrovascular accident (CVA), major CV surgery or percutaneous coronary intervention (PCI), cardiac device implantation or blood transfusion; on active cardiac transplant list; left ventricular assist device implanted
6. Any of the following comorbidities: active infection (if the patient is suffering from a significant ongoing infection as judged by the investigator recruitment should be postponed until the infection has passed or is controlled by antibiotics), other disease with life expectancy of <2 years, active clinically relevant bleeding in the investigators opinion, known or suspected gastrointestinal malignancy
7. Pregnancy or women of childbearing potential (i.e. continuing menstrual cycle) not using effective contraception
8. Contraindication to IV iron in the investigator’s opinion according to current approved Summary of Product Characteristics: hypersensitivity to the active substance, to Monofer® or any of its excipients (water for injections, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment)); known serious hypersensitivity to other parenteral iron products; noniron deficiency anaemia (e.g. haemolytic anaemia); iron overload or disturbances in utilisation of iron (e.g. haemochromatosis, haemosiderosis); decompensated liver cirrhosis and hepatitis
9. Participation in another intervention study involving a drug or device within the past 90 days (coenrolment In observational studies is permitted)

Recruitment start date

25/08/2016

Recruitment end date

31/08/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Queen Alexandra Hospital
Portsmouth Hospitals NHS Trust Southwick Hill Road Cosham
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Glasgow Royal Infirmary
84 Castle Street
Glasgow
G4 0ET
United Kingdom

Trial participating centre

Golden Jubilee National Hospital
Agamemnon Street
Clydebank
G81 4DY
United Kingdom

Trial participating centre

Queen Elizabeth University Hospital
1345 Govan Road, Govan
Glasgow
G51 4TF
United Kingdom

Trial participating centre

Salford Royal Hospital
Stott Lane
Salford
M6 8HD
United Kingdom

Trial participating centre

Glenfield Hospital
University of Leicester Clinical Science Wing
Leicester
LE3 9QP
United Kingdom

Trial participating centre

Royal Sussex County Hosptial
Eastern Road
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Great Western Hospital
Marlborough Road
Swindon
SN3 6BB
United Kingdom

Trial participating centre

Ninewells Hospital and Medical School
Division of Cardiovascular & Diabetes Medicine Mailbox 2
Dundee
DD1 9SY
United Kingdom

Trial participating centre

Basingstoke and North Hampshire Hospital
Aldermaston Rd
Basingstoke
RG24 9NA
United Kingdom

Trial participating centre

Raigmore Hospital
Old Perth Road
Inverness
IV2 3UJ
United Kingdom

Trial participating centre

Aintree University Hospital
Longmoor Lane
Liverpool
L9 7AL
United Kingdom

Sponsor information

Organisation

University of Glasgow

Sponsor details

University Avenue
Glasgow
G12 8QQ
United Kingdom
+44 141 232 1798
Debra.Stuart@glasgow.ac.uk

Sponsor type

University/education

Website

Organisation

NHS Greater Glasgow & Clyde Research and Development

Sponsor details

Management Office
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SJ
United Kingdom
+44 141 232 1813
maureen.travers@ggc.scot.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

British Heart Foundation

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Funder name

Pharmacosmos UK Ltd.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The study protocol and a description of the recruitment experience and participant baseline characteristics will be published before study completion. On completion of the trial, the database will be locked and analysed by staff of the Robertson Centre for Biostatistics, University of Glasgow. A final study report will be prepared and the results will be published in a major medical journal in January 2021.

IPD Sharing plan:
The data sharing plans for the current study are not fully formulated and will be made available at a later date. However they will be based on the following strategy:
The study database will be held at the Robertson Centre for Biostatistics University of Glasgow. After planned publications have been completed, the study Publications Committee will review applications for additional data analyses, data access, collaborative analyses (eg meta-analyses and pooling projects). In considering these requests, the Publications Committee will take into account the cost of meeting requests, the scientific validity of the requests, overlap with other requests, other legal and ethical issues, patient consent issues and information governance issues.

Intention to publish date

31/01/2021

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes