Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency: IRONMAN (IRONMAN)

October 27, 2022 updated by: Paul Kalra, University of Glasgow

Effectiveness of Intravenous Iron Treatment vs Standard Care in Patients With Heart Failure and Iron Deficiency: a Randomised, Open-label Multicentre Trial (IRONMAN)

This study will address whether the additional use of Intravenous (IV) iron on top of standard care will improve the outlook for patients with heart failure and iron deficiency. One group of participants will receive treatment with iron injections and the other group will not receive any iron injections.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Chronic heart failure (CHF) is a very common medical problem. Despite improvements in treatment, many patients suffer limiting symptoms of shortness of breath and fatigue. Hospitalisation for CHF is common and life expectancy reduced. Many patients with CHF have a deficiency of iron (low iron levels or cannot use iron properly), and this is associated with poorer outcomes. Some small research studies have suggested that giving patients intravenous iron improves symptoms in the short term. It is unknown, however, whether correcting iron deficiency is beneficial to patients with CHF in the long term and whether it improves life expectancy and keeps them out of hospital. This study will help us answer these key questions.

This study will address whether the additional use of Intravenous (IV) iron on top of standard care will improve the outlook for patients with heart failure and iron deficiency. One group of participants will receive treatment with iron injections and the other group will not receive any iron injections.

The study will take place in about 70 secondary care sites (hospitals) across the UK. Participants will be recruited over a period of about five years and will be followed up for a minimum of three months (average duration of about four years per participant). After the initial visits, participants will be seen every four months.

Study Type

Interventional

Enrollment (Anticipated)

1160

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Aberdeen, United Kingdom
        • Aberdeen Royal Infirmary
      • Airdrie, United Kingdom
        • University Hospital Monklands
      • Antrim, United Kingdom
        • Antrim Area Hospital
      • Ashington, United Kingdom
        • Wansbeck General Hospital
      • Barnet, United Kingdom
        • Barnet Hospital
      • Basildon, United Kingdom
        • Basildon University Hospital
      • Basingstoke, United Kingdom
        • Basingstoke And North Hampshire Hospital
      • Belfast, United Kingdom
        • Royal Victoria Hospital
      • Blackpool, United Kingdom
        • Blackpool Victoria Hospital
      • Bournemouth, United Kingdom
        • Royal Bournemouth Hospital
      • Bradford, United Kingdom
        • Bradford Royal Infirmary
      • Bridgend, United Kingdom
        • Princess of Wales Hospital
      • Brighton, United Kingdom
        • Royal Sussex County Hospital
      • Bristol, United Kingdom
        • Bristol Royal Infirmary
      • Chelmsford, United Kingdom
        • Broomfield Hospital
      • Chesterfield, United Kingdom
        • Chesterfield Royal Hospital
      • Chichester, United Kingdom
        • St. Richard's Hospital
      • Coventry, United Kingdom
        • University Hospital Coventry
      • Croydon, United Kingdom
        • Croydon University Hospital
      • Darlington, United Kingdom
        • Darlington Memorial Hospital
      • Doncaster, United Kingdom
        • Doncaster Royal Infirmary
      • Dundee, United Kingdom
        • Ninewells Hospital
      • Dundonald, United Kingdom
        • Ulster Hospital
      • Eastbourne, United Kingdom
        • Eastbourne District General Hospital
      • Edinburgh, United Kingdom
        • Royal Infirmary of Edinburgh
      • Exeter, United Kingdom
        • Royal Devon and Exeter Hospital
      • Glasgow, United Kingdom
        • Glasgow Royal Infirmary
      • Glasgow, United Kingdom
        • Queen Elizabeth University Hospital
      • Glasgow, United Kingdom
        • Golden Jubilee National Hospital
      • Harefield, United Kingdom
        • Harefield Hospital
      • High Wycombe, United Kingdom
        • Wycombe General Hospital
      • Hull, United Kingdom
        • Castle Hill Hospital
      • Inverness, United Kingdom
        • Raigmore Hospital
      • Isleworth, United Kingdom
        • West Middlesex University Hospital
      • Kilmarnock, United Kingdom
        • University Hospital Crosshouse
      • Kingston upon Thames, United Kingdom
        • Kingston Hospital
      • Kirkcaldy, United Kingdom
        • Victoria Hospital
      • Larbert, United Kingdom
        • Forth Valley Royal Hospital
      • Leicester, United Kingdom
        • Glenfield Hospital
      • Liverpool, United Kingdom
        • Aintree University Hospital
      • Liverpool, United Kingdom
        • Liverpool Heart and Chest Hospital
      • Llandough, United Kingdom
        • University Hospital Llandough
      • Llantrisant, United Kingdom
        • Royal Glamorgan Hospital
      • London, United Kingdom
        • University College London Hospital
      • London, United Kingdom
        • North Middlesex University Hospital
      • London, United Kingdom
        • King's College Hospital
      • London, United Kingdom
        • St. Bartholomew's Hospital
      • London, United Kingdom
        • Guy's and St. Thomas' Hospital
      • London, United Kingdom
        • Hammersmith Hospital (Imperial College)
      • Manchester, United Kingdom
        • Manchester Royal Infirmary
      • Manchester, United Kingdom
        • Wythenshawe Hospital
      • Newport, United Kingdom
        • Royal Gwent Hospital
      • Nottingham, United Kingdom
        • Nottingham University Hospital
      • Oldham, United Kingdom
        • Royal Oldham Hospital
      • Oxford, United Kingdom
        • John Radcliffe Hospital
      • Paisley, United Kingdom
        • Royal Alexandra Hospital
      • Poole, United Kingdom
        • Poole Hospital
      • Portsmouth, United Kingdom
        • Queen Alexandra Hospital
      • Salford, United Kingdom
        • Salford Royal Hospital
      • Salisbury, United Kingdom
        • Salisbury District Hospital
      • Sheffield, United Kingdom
        • Northern General Hospital
      • Southampton, United Kingdom
        • University Hospital Southampton
      • Southend, United Kingdom
        • Southend University Hospital
      • Stoke-on-Trent, United Kingdom
        • Royal Stoke University Hospital
      • Sunderland, United Kingdom
        • City Hospitals Sunderland
      • Swansea, United Kingdom
        • Morriston Hospital
      • Swindon, United Kingdom
        • Great Western Hospital
      • Tooting, United Kingdom
        • St. George's Hospital
      • Torquay, United Kingdom
        • Torbay Hospital
      • Truro, United Kingdom
        • Royal Cornwall Hospital
      • Watford, United Kingdom
        • Watford General Hospital
      • Wolverhampton, United Kingdom
        • New Cross Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  1. Age ≥18 years
  2. LVEF ≤45% within the prior two years using any conventional imaging modality (this should be the most recent assessment of LVEF)
  3. New York Heart Association (NYHA) class II - IV
  4. Iron deficient - defined as TSAT <20% and/or ferritin <100 ug/L
  5. Evidence of being in a higher risk HF group: (a) Current (with the expectation that patient will survive to discharge) or recent (within 6 months) hospitalisation for HF, OR (b) Out-patients with NT-proBNP >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

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/CKD-EPI estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2
  3. Already planned to receive IV iron
  4. Likely to need or already receiving erythropoiesis stimulating agents (ESA)
  5. Any of the following apply: (a) planned cardiac surgery or revascularisation; (b) within 3 months of any of the following: 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), or blood transfusion; (c) on active cardiac transplant list; (d) 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 investigator's opinion, known or suspected gastro-intestinal malignancy
  7. Pregnancy, women of childbearing potential (i.e. continuing menstrual cycle) not using effective contraception (see Appendix 3) or breast-feeding women
  8. Contra-indication 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; non-iron deficiency anaemia (e.g. haemolytic anaemia); iron overload or disturbances in utilisation of iron (e.g. haemochromatosis, haemosiderosis); decompensated liver disease.
  9. Participation in another intervention study involving a drug or device within the past 90 days (co-enrolment in observational studies is permitted)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard care
Participants in this arm will receive their usual care
Experimental: Standard care plus IV iron infusion

Iron to be administered as iron (III) isomaltoside 1000 / ferric derisomaltose.

Infused over a minimum of 15 mins for doses up to and including 1000mg, and a minimum of 30 mins for doses >1000mg

Where Hb ≥10 g/dL, dosage according to body weight is as follows:

Body weight <50 kg: 20 mg/kg; Body weight 50 to <70 kg: 1000 mg; Body weight ≥70 kg: 20 mg/kg up to a maximum of 1500 mg.

Where Hb <10 g/dL, dosage according to body weight is as follows:

Body weight <50 kg: 20 mg/kg; Body weight 50 to <70 kg: 20 mg/kg; Body weight ≥70 kg: 20 mg/kg up to a maximum of 2000 mg.
Drug: Ferric Derisomaltose
Other Names:
  • Monofer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
CV mortality or hospitalisation for worsening heart failure (analysis will include first and recurrent hospitalisations)
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited

Secondary Outcome Measures

Outcome Measure
Time Frame
Hospitalisation for worsening heart failure (recurrent events)
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited
CV hospitalisation (first event)
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited
CV death or hospitalisation for heart failure analysed as time to first event
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited
Overall Score from Minnesota Living with Heart Failure
Time Frame: At 4 months
At 4 months
Cardiovascular mortality
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited
Overall EQ-5D VAS
Time Frame: At 4 months
At 4 months
Overall EQ-5D index
Time Frame: At 4 months
At 4 months
CV mortality or hospitalisation for major CV event (stroke, MI, heart failure) (first event)
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited
All-cause mortality
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited
All-cause hospitalisation (first event)
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited
Combined all-cause mortality or first all-cause unplanned hospitalisation
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited
Physical domain of QoL (Minnesota Living With Heart Failure)
Time Frame: At 4 months
At 4 months
Physical domain of QoL (Minnesota Living With Heart Failure)
Time Frame: At 20 months
At 20 months
Overall EQ-5D VAS
Time Frame: At 20 months
At 20 months
Overall EQ-5D index
Time Frame: At 20 months
At 20 months
Overall Score from Minnesota Living With Heart Failure
Time Frame: At 20 months
At 20 months
Days dead or hospitalised
Time Frame: At 36 months
At 36 months
Quality-adjusted days alive and out of hospital
Time Frame: At 12 months
At 12 months
6 minute walk test
Time Frame: At 4 months
At 4 months
6 minute walk test
Time Frame: At 20 months
At 20 months
Death due to infection
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited
Hospitalisation primarily for infection (first event)
Time Frame: Minimum of 3 months follow-up from last patient recruited
Minimum of 3 months follow-up from last patient recruited

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Glasgow

Collaborators

Pharmacosmos A/S
British Heart Foundation
NHS Greater Glasgow and Clyde

Investigators

  • Study Chair: Nicholas Boon, Chair of Steering Committee (Retired)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2016

Primary Completion (Actual)

August 26, 2022

Study Completion (Actual)

August 26, 2022

Study Registration Dates

First Submitted

December 24, 2015

First Submitted That Met QC Criteria

December 29, 2015

First Posted (Estimate)

December 30, 2015

Study Record Updates

Last Update Posted (Actual)

October 28, 2022

Last Update Submitted That Met QC Criteria

October 27, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GN15CA190

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Applications for data access will be considered when analysis of the main pre-specified endpoints, sub-groups and sub-studies, and other sub-analyses have been completed.

IPD Sharing Time Frame

Applications for access will be considered when analysis of the main pre-specified endpoints, sub-groups and sub-studies, and other sub-analyses have been completed.

IPD Sharing Access Criteria

Applications for access will be reviewed by the study Steering Committee.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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