IRONHEART: Intravenous Iron in Non-ischaemic Heart Failure (IRONHEART)

Immediate Effects of Intravenous Iron Therapy in Patients With Systolic Heart Failure and Iron Deficiency as Evaluated by Cardiac Magnetic Resonance Imaging: An Observational Prospective Study

The aim of this study is to observe the effect of intravenous ferric derisomaltose in participants with non-ischaemic heart failure (LVEF<40%), iron deficiency (TSATS<20%) and established on heart failure therapy including Sodium-glucose cotransporter 2 inhibitors (SGLT2i). Participants will undergo baseline laboratory blood tests, cardiac magnetic resonance imaging (cMRI), six-minute walk test, musculoskeletal function test and Kansas City Cardiomyopathy Questionnaire (KCCQ). These investigations will be repeated at 24 hours and 30 days after the administration of intravenous ferric derisomaltose.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Iron Deficiencies
• Intervention / Treatment: Drug: Ferric derisomaltose

Detailed Description

Heart failure is a neuro-endocrine syndrome in which patients report symptoms of breathlessness and lethargy accompanied with signs of fluid overload.

Iron deficiency is very common in heart failure, affecting up to 50% of patients. Its presence in this population is associated with worsening symptoms and increased risk of death. Human clinical trials have shown that administering intravenous iron improves quality of life and exercise tolerance. The European Society Guidelines gives a 1A class recommendation for intravenous iron replacement in symptomatic heart failure patients.

Iron is an essential micro-nutrient required in mitochondrial metabolism, handling of reactive oxygen species and cellular metabolism. Heart failure leads to a pro inflammatory state, resulting in reduced gastrointestinal absorption, and inhibition of iron mobilisation. Mouse models have shown reversal of cardiac fibrosis, cardiac remodelling, and reduction in the pro inflammatory state when treated with intravenous iron. Similarly iron deficient human cardiomyocytes show adverse remodelling and altered function reversed with iron repletion.

The investigators aim to recruit 16 participants with non-ischaemic heart failure, established on optimal medical therapy, including SGLT2i therapy, for four weeks prior to the start of the trial. Initial baseline investigations will include: cMRI, six-minute walk test, hand grip strength test, laboratory blood tests and a KCCQ-12. Intravenous ferric derisomaltose will be given as standard of care. These investigations will be repeated at 24 hours and at 30 days after the administration of intravenous ferric derisomaltose.

The study aims to observe changes pre and post administration of intravenous derisomaltose in the following:

• Changes in cardiac function and parametric measurements (T1/T2) as assessed by cardiac magnetic resonance imaging.
• Changes in high sensitivity troponin, N Terminal pro-Brain Natriuretic Peptide (NT pro-BNP) and serum phosphate levels.
• Changes in the submaximal exercise test (six-minute walk) and musculoskeletal function test (hand grip test).
• Changes in heart failure symptoms as assessed by KCCQ Questionnaire.

• Study Type: Observational
• Enrollment (Estimated): 16

Contacts and Locations

• Study Contact: Name: Rachael Pulham; Phone Number: +442381205044; Email: sponsor@uhs.nhs.uk
• Study Contact Backup: Name: Flett; Phone Number: +442381205906; Email: andrew.flett@uhs.nhs.uk

Study Locations

• United Kingdom
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Recruiting
      • University Hospital Southampton NHS Foundation Trust
      • Contact: Andrew S Flett, MBBS BSc MD; Phone Number: +442381205906; Email: andrew.flett@uhs.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants with non-ischaemic cardiomyopathy with a left ventricular function less than 40% and iron deficient as per the following criteria: Transferrin saturations < 20%

Description

Inclusion Criteria:

• Participants capable of giving informed consent.
• Aged 18yrs and above.
• Diagnosed with heart failure and a reduction of their ejection fraction < 40% by any modality.
• Non ischaemic cardiomyopathy as determined by baseline cardiac magnetic resonance imaging.
• Iron deficient per this definition: Transferrin saturations < 20%.
• Established on Heart failure therapy including SGLT2i therapy for a minimum of four weeks prior to recruitment.
• New York Heart Association score of I - III class.

Exclusion Criteria:

• New York Heart Association classification Score >IV
• Ischaemic cardiomyopathy
• Chronic kidney stage: Estimated Glomerular Filtration Rate (eGFR) < 30
• Requirement for renal dialysis
• Atrial fibrillation / atrial flutter
• Non cardiac and cardiac palliative diagnosis
• Active cancer diagnosis
• Moderate to severe valvular heart disease
• Cardiac electronic implantable device: Cardiac resynchronization therapy, Implantable cardioverter-defibrillator, left ventricular assist device
• Cardiac & non cardiac transplant participants
• Myocardial infarction, Percutaneous Coronary Intervention, Coronary Artery Bypass Graft surgery in the last 30 days
• Complex congenital heart disease
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

IRONHEART Observational Study Group; 16 participants, with non-ischaemic heart failure, with iron deficiency TSATS <20% and heart failure with a reduced ejection fraction <40%. Cohort will have to be established on guideline directed heart failure therapy. Participants meeting eligibility criteria will undergo baseline quality of life questionnaires, hand grip tests and six minute walk tests before receiving intravenous iron derisomaltose and repeating these investigations again after 24 hours and 30 days including a cardiac magnetic resonance imaging.

Drug: Ferric derisomaltose; See group descriptions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ejection Fraction quantified on Cardiac Magnetic Resonance Imaging	Changes in Ejection Fraction quoted in (%)	24 Hours and 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T1 Mapping quantified on Cardiac Magnetic Resonance Imaging	Changes in T1 Parametric Mapping quantified in (msec)	24 Hours and 30 days
T2 Mapping quantified on Cardiac Magnetic Resonance Imaging	Changes in T2 Parametric Mapping quantified in (msec)	24 Hours and 30 Days
Extracellular Volume (ECV) Fraction quantified on Cardiac Magnetic Resonance Imaging	Changes in ECV Fraction quoted in (%)	24 Hours and 30 Days
Ventricular Volumes quantified on Cardiac Magnetic Resonance Imaging	Changes in left and right ventricular volumes quantified in (ml)	24 Hours and 30 Days
Indexed Ventricular Volume quantified on Cardiac Magnetic Resonance Imaging	Changes in indexed left and right ventricular volumes. Weight and Height will be combined to calculate Body Surface Area (m2). Left Ventricular Volume in (ml) will be divided by Body Surface Area to give indexed value (ml/m2)	24 Hours and 30 Days
Strain analysis as quantified on Cardiac Magnetic Resonance Imaging	Changes in strain as assessed by feature tracking on cardiac magnetic resonance imaging	24 Hours and 30 Days
Quality of Life assessment: KCCQ-12 questionnaire	Changes in Kansas City Cardiomyopathy Questionnaire. Four sub-domains: Physical limitation, Symptom Frequency, Quality of life and social limitations. Scores range from 0 - 100, with higher scores reflecting a better heart status.	24 Hours and 30 Days
Submaximal Exercise Test: Six Minute Walk Test	Changes in distance walked (meters) in six minutes	24 Hours and 30 Days
Musculoskeletal function test: Hand grip test	Changes in Isometric Grip Force in (KG)	24 Hours and 30 Days
Haemoglobin	Laboratory Blood Test	30 Days
High Sensitivity troponin	Laboratory Blood Test	24 Hours and 30 Days
Phosphate	Laboratory Blood Test	24 Hours and 30 Days
N-terminal pro B type natriuretic peptide (NTproBNP)	Laboratory Blood Test	30 Days

Collaborators and Investigators

• Sponsor: University Hospital Southampton NHS Foundation Trust
• Collaborators: Portsmouth Hospitals NHS Trust
• Investigators: Principal Investigator: Andrew S Flett, MBBS BSc MD, University Hospital Southampton NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: July 2, 2024
• First Submitted That Met QC Criteria: August 5, 2024
• First Posted (Actual): August 7, 2024

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 5, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Cardiac MRI; Iron deficiency; Iron homeostasis; Chronic heart failure; Ferric derisomaltose; Left ventricular failure; Non-ischaemic heart failure; Cardiac Magnetic resonance imaging
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Heart Failure; Anemia, Iron-Deficiency; Iron Deficiencies
• Other Study ID Numbers: RHMCAR0640

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