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

Chronic Heart Failure Clinical Trial

— IRONMAN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02642562
• Other study ID #: GN15CA190
• Status: Completed
• Phase: Phase 4
• Start date: August 2016
• Est. completion date: August 26, 2022

Study information

• Verified date: October 2022
• Source: University of Glasgow
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1160
• Est. completion date: August 26, 2022
• Est. primary completion date: August 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Chronic Heart Failure
• Heart Failure
• Iron Deficiency
• Left Ventricular Systolic Dysfunction

Intervention

Drug:
• Ferric Derisomaltose

Locations

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

Sponsors (4)

Lead Sponsor	Collaborator
University of Glasgow	British Heart Foundation, NHS Greater Glasgow and Clyde, Pharmacosmos A/S

Country where clinical trial is conducted

United Kingdom, 

Outcome

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