Heart failure - IRONMAN

The clinical question

Many people with heart failure also lack iron in their blood, which is linked to more severe symptoms, like poorer exercise capacity and an increased risk of being admitted to hospital or even dying. Several short term studies had shown that giving iron injections through a vein to heart failure patients improved their quality of life and ability to exercise. But would regularly supplementing iron in this way help improve the health of people with heart failure in the longer term? The IRONMAN clinical trial led by Professor Paul Kalra from Portsmouth Hospitals University NHS Trust with Trial Director Professor Ian Ford from the University of Glasgow tested this out.

What did the study involve?

From 2016 to 2021, IRONMAN recruited 1137 people with heart failure and low iron levels from 70 hospitals in the United Kingdom. People volunteering for the trial had blood taken to establish if their iron levels were low. If blood tests showed that they were iron deficient, they were invited to participate. Participants were randomly assigned to either:

• Have regular injections of iron through a vein as well as their normal heart failure treatments. Participants visited the hospital every four months where they had their iron levels measured. If their levels were low, iron was given through an intravenous drip over 30 minutes and they stayed for 30 minutes afterwards for observation.
• Continue their usual heart failure treatment.

The investigators were asked to check that everyone in the trial received the best possible heart failure care recommended by national guidelines.

All participants were invited to have four monthly hospital visits, where they had blood tests, a physical examination, and were asked about their health and whether they’d been admitted to hospital for any reason. There is a theoretical possibility that intravenous iron may increase the risk of infection, so the research team checked whether participants had experienced an infection or were admitted to hospital or died because of an infection. Participant outcomes were also tracked using routine electronic health care records.

What did the study show?

• People in the study were followed-up for an average of 2.7 years. Most of the people in the iron group (78 per cent) received just one or two intravenous iron infusions during this time.
• The risk of being hospitalised for heart failure or dying from a heart related cause was 18 per cent lower in the group given iron infusions compared with usual care.
• People who received iron infusions also reported a better quality of life at four months.
• There was no difference between the groups in the number of infections causing hospitalisation or death.
• The trial was severely affected by the Covid-19 pandemic. Many participants were unable or unwilling to attend research visits to have their iron levels checked, so it is likely that some people missed out on receiving an iron infusion, potentially diluting the benefit seen from iron.
• Because of this, the researchers also looked at the data from the 1063 people who were part of the trial before 31 March 2020 and whose treatment wouldn’t have been as affected by the pandemic. This analysis showed an even stronger benefit of iron infusions over usual care.

Why is the study important?

The IRONMAN trial showed for the first time that regular intravenous iron infusions benefitted a broad range of people with heart failure and iron deficiency in the longer term, and that the treatment was safe.

Professor Kalra reflected on the challenges of progressing the trial during the Covid-19 pandemic when he presented the results of IRONMAN at the 2022 American Heart Association Meeting: ‘We (the whole trial team), and our patients, were very pleased that we were able to complete the trial, despite the pandemic. We are grateful for the commitment of everyone who was involved in the trial.

He continued: “Despite great advances in treatment and care in recent decades, many people with heart failure still have symptoms that impact their daily lives and rates of hospital admissions remain high. We’ve shown that an infusion of iron (that’s takes around 60 minutes), repeated when needed, can correct iron deficiency for people with heart failure and help improve their wellbeing and keep them out of hospital."

Study details

Effectiveness of intravenous iron treatment vs standard care in patients with heart failure and iron deficiency: a randomised, open-label multicentre trial (IRON-MAN) 
Award reference: CS/15/1/31175
Principal Investigator: Professor Paul Kalra, University of Glasgow
Trial registration number: NCT02642562

Publication details

Kalra PR, Cleland JGF, Petrie MC, et al. 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.