NCT02642562

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,160

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Aug 2016

Longer than P75 for phase_4

Geographic Reach
1 country

72 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 24, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 30, 2015

Completed
7 months until next milestone

Study Start

First participant enrolled

August 1, 2016

Completed
6.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 26, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 26, 2022

Completed
Last Updated

October 28, 2022

Status Verified

October 1, 2022

Enrollment Period

6.1 years

First QC Date

December 24, 2015

Last Update Submit

October 27, 2022

Conditions

Keywords

Intravenous ironPROBE design

Outcome Measures

Primary Outcomes (1)

  • CV mortality or hospitalisation for worsening heart failure (analysis will include first and recurrent hospitalisations)

    Minimum of 3 months follow-up from last patient recruited

Secondary Outcomes (22)

  • Hospitalisation for worsening heart failure (recurrent events)

    Minimum of 3 months follow-up from last patient recruited

  • CV hospitalisation (first event)

    Minimum of 3 months follow-up from last patient recruited

  • CV death or hospitalisation for heart failure analysed as time to first event

    Minimum of 3 months follow-up from last patient recruited

  • Overall Score from Minnesota Living with Heart Failure

    At 4 months

  • Cardiovascular mortality

    Minimum of 3 months follow-up from last patient recruited

  • +17 more secondary outcomes

Study Arms (2)

Standard care

NO INTERVENTION

Participants in this arm will receive their usual care

Standard care plus IV iron infusion

EXPERIMENTAL

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

Interventions

Also known as: Monofer
Standard care plus IV iron infusion

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 years
  • LVEF ≤45% within the prior two years using any conventional imaging modality (this should be the most recent assessment of LVEF)
  • New York Heart Association (NYHA) class II - IV
  • Iron deficient - defined as TSAT \<20% and/or ferritin \<100 ug/L
  • 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)
  • Able and willing to provide informed consent

You may not qualify if:

  • 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)
  • MDRD/CKD-EPI estimated glomerular filtration rate (eGFR) \<15ml/min/1.73m2
  • Already planned to receive IV iron
  • Likely to need or already receiving erythropoiesis stimulating agents (ESA)
  • 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.
  • 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
  • Pregnancy, women of childbearing potential (i.e. continuing menstrual cycle) not using effective contraception (see Appendix 3) or breast-feeding women
  • 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.
  • Participation in another intervention study involving a drug or device within the past 90 days (co-enrolment in observational studies is permitted)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (72)

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

University Hospital Monklands

Airdrie, United Kingdom

Location

Antrim Area Hospital

Antrim, United Kingdom

Location

Wansbeck General Hospital

Ashington, United Kingdom

Location

Barnet Hospital

Barnet, United Kingdom

Location

Basildon University Hospital

Basildon, United Kingdom

Location

Basingstoke and North Hampshire Hospital

Basingstoke, United Kingdom

Location

Royal Victoria Hospital

Belfast, United Kingdom

Location

Blackpool Victoria Hospital

Blackpool, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Bradford Royal Infirmary

Bradford, United Kingdom

Location

Princess of Wales Hospital

Bridgend, United Kingdom

Location

Royal Sussex County Hospital

Brighton, United Kingdom

Location

Bristol Royal Infirmary

Bristol, United Kingdom

Location

Broomfield Hospital

Chelmsford, United Kingdom

Location

Chesterfield Royal Hospital

Chesterfield, United Kingdom

Location

St. Richard's Hospital

Chichester, United Kingdom

Location

University Hospital Coventry

Coventry, United Kingdom

Location

Croydon University Hospital

Croydon, United Kingdom

Location

Darlington Memorial Hospital

Darlington, United Kingdom

Location

Doncaster Royal Infirmary

Doncaster, United Kingdom

Location

Ninewells Hospital

Dundee, United Kingdom

Location

Ulster Hospital

Dundonald, United Kingdom

Location

Eastbourne District General Hospital

Eastbourne, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, United Kingdom

Location

Golden Jubilee National Hospital

Glasgow, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

Harefield Hospital

Harefield, United Kingdom

Location

Wycombe General Hospital

High Wycombe, United Kingdom

Location

Castle Hill Hospital

Hull, United Kingdom

Location

Raigmore Hospital

Inverness, United Kingdom

Location

West Middlesex University Hospital

Isleworth, United Kingdom

Location

University Hospital Crosshouse

Kilmarnock, United Kingdom

Location

Kingston Hospital

Kingston upon Thames, United Kingdom

Location

Victoria Hospital

Kirkcaldy, United Kingdom

Location

Forth Valley Royal Hospital

Larbert, United Kingdom

Location

Glenfield Hospital

Leicester, United Kingdom

Location

Aintree University Hospital

Liverpool, United Kingdom

Location

Liverpool Heart and Chest Hospital

Liverpool, United Kingdom

Location

University Hospital Llandough

Llandough, United Kingdom

Location

Royal Glamorgan Hospital

Llantrisant, United Kingdom

Location

Guy's and St. Thomas' Hospital

London, United Kingdom

Location

Hammersmith Hospital (Imperial College)

London, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

North Middlesex University Hospital

London, United Kingdom

Location

St. Bartholomew's Hospital

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

Manchester Royal Infirmary

Manchester, United Kingdom

Location

Wythenshawe Hospital

Manchester, United Kingdom

Location

Royal Gwent Hospital

Newport, United Kingdom

Location

Nottingham University Hospital

Nottingham, United Kingdom

Location

Royal Oldham Hospital

Oldham, United Kingdom

Location

John Radcliffe Hospital

Oxford, United Kingdom

Location

Royal Alexandra Hospital

Paisley, United Kingdom

Location

Poole Hospital

Poole, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, United Kingdom

Location

Salford Royal Hospital

Salford, United Kingdom

Location

Salisbury District Hospital

Salisbury, United Kingdom

Location

Northern General Hospital

Sheffield, United Kingdom

Location

University Hospital Southampton

Southampton, United Kingdom

Location

Southend University Hospital

Southend, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, United Kingdom

Location

City Hospitals Sunderland

Sunderland, United Kingdom

Location

Morriston Hospital

Swansea, United Kingdom

Location

Great Western Hospital

Swindon, United Kingdom

Location

St. George's Hospital

Tooting, United Kingdom

Location

Torbay Hospital

Torquay, United Kingdom

Location

Royal Cornwall Hospital

Truro, United Kingdom

Location

Watford General Hospital

Watford, United Kingdom

Location

New Cross Hospital

Wolverhampton, United Kingdom

Location

Related Publications (5)

  • Sze S, Squire I, Kalra PR, Cleland JG, Petrie MC, Kalra PA, Ahmed F, Banerjee P, Boos CJ, Chapman C, Cowburn PJ, Dixon L, Duckett S, Lane R, Foley P, Lang NN, Lyons K, Ray R, Schiff R, Thomson EA, Robertson M, Ford I; IRONMAN Study group. Age-stratified effects of intravenous ferric derisomaltose in heart failure with iron deficiency: insights from the IRONMAN trial. Heart. 2025 Jun 13;111(13):634-641. doi: 10.1136/heartjnl-2024-324908.

  • Foley PW, Kalra PR, Cleland JGF, Petrie MC, Kalra PA, Squire I, Campbell P, Chapman C, Donnelly P, Graham F, Hannah A, Lang NN, Matthews I, Leslie SJ, Pellicori P, Piper S, Ray R, Savage HO, Spencer C, Walsh J, Wong YK, Ford I; on behalf of the IRONMAN Study Group. Effect of correcting iron deficiency on the risk of serious infection in heart failure: Insights from the IRONMAN trial. Eur J Heart Fail. 2025 Jan;27(1):166-173. doi: 10.1002/ejhf.3504. Epub 2024 Oct 25.

  • Cleland JGF, Pellicori P, Graham FJ, Lane R, Petrie MC, Ahmed F, Squire IB, Ludman A, Japp A, Al-Mohammad A, Clark AL, Szwejkowski B, Critoph C, Chong V, Schiff R, Nageh T, Glover J, McMurray JJV, Thomson EA, Robertson M, Ford I, Kalra PA, Kalra PR; IRONMAN Study Group. Adjudication of Hospitalizations and Deaths in the IRONMAN Trial of Intravenous Iron for Heart Failure. J Am Coll Cardiol. 2024 Oct 29;84(18):1704-1717. doi: 10.1016/j.jacc.2024.08.052.

  • Kalra PR, Cleland JGF, Petrie MC, Thomson EA, Kalra PA, Squire IB, Ahmed FZ, Al-Mohammad A, Cowburn PJ, Foley PWX, Graham FJ, Japp AG, Lane RE, Lang NN, Ludman AJ, Macdougall IC, Pellicori P, Ray R, Robertson M, Seed A, Ford I; IRONMAN Study Group. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet. 2022 Dec 17;400(10369):2199-2209. doi: 10.1016/S0140-6736(22)02083-9. Epub 2022 Nov 5.

  • Kalra PR, Cleland JG, Petrie MC, Ahmed FZ, Foley PW, Kalra PA, Lang NN, Lane RE, Macdougall IC, Pellicori P, Pope MTB, Robertson M, Squire IB, Thomson EA, Ford I. Rationale and design of a randomised trial of intravenous iron in patients with heart failure. Heart. 2022 Nov 24;108(24):1979-1985. doi: 10.1136/heartjnl-2022-321304.

MeSH Terms

Conditions

Iron DeficienciesVentricular Dysfunction, Left

Interventions

ferric derisomaltose

Condition Hierarchy (Ancestors)

Iron Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesVentricular DysfunctionHeart DiseasesCardiovascular Diseases

Study Officials

  • Nicholas Boon

    Chair of Steering Committee (Retired)

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief Investigator

Study Record Dates

First Submitted

December 24, 2015

First Posted

December 30, 2015

Study Start

August 1, 2016

Primary Completion

August 26, 2022

Study Completion

August 26, 2022

Last Updated

October 28, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP
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.
Access Criteria
Applications for access will be reviewed by the study Steering Committee.

Locations