Intravenous Iron to Improve Symptoms, Quality of Life and Exercise Capacity in HFpEF With Iron Deficiency

NCT07643818 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2026HREC02
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate whether intravenous (IV) iron improves symptoms, exercise capacity, and quality of life in patients with heart failure with preserved ejection fraction (HFpEF) and iron deficiency. Iron deficiency is common in heart failure and is associated with worse symptoms, reduced physical activity, poorer quality of life, and increased hospitalisation risk. Intravenous iron therapy has demonstrated clinical benefit in patients with heart failure with reduced ejection fraction (HFrEF), but evidence in HFpEF remains limited. ISLE-HFpEF is a prospective, randomised, double-blind, placebo-controlled trial enrolling 150 adults with symptomatic HFpEF and iron deficiency. Participants will be randomised in a 1:1 ratio to receive either intravenous ferric derisomaltose (Monofer) or placebo (0.9% sodium chloride). Participants will undergo baseline assessment, treatment infusion, and 12-week follow-up. The primary outcome is change in 6-minute walk distance at 12 weeks. Secondary outcomes include change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score, physical activity measured using wearable accelerometers, transferrin saturation, NT-proBNP, and New York Heart Association (NYHA) functional class. The study will also evaluate the feasibility and utility of continuous digital monitoring using wearable technologies, including a thigh-worn SENS Motion accelerometer and the Oura Ring, to assess real-world physical activity and cardiovascular physiology throughout the study period.

Conditions

Heart Failure With Preserved Ejection Fraction (HFpEF

Keywords

HFpEF; Iron; Heart Failure

Outcome Measures

Primary Outcomes (1)

• Change in 6-minute walk distance (6MWD)

  Difference in 6-minute walk distance from baseline to 12 weeks following treatment with intravenous ferric derisomaltose or placebo in participants with HFpEF and iron deficiency.

  Baseline and 12 weeks post-treatment.

Secondary Outcomes (6)

• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score

  Baseline and 12 weeks post-treatment.

• Change in transferrin saturation (TSAT)

  Baseline and 12 weeks post-treatment.

• Change in NT-proBNP

  Baseline and 12 weeks post-treatment.

• Change in total daily step count

  Baseline 2-week period and final 2-week period prior to 12-week follow-up.

• Change in time spent in sedentary behaviour

  Baseline 2-week period and final 2-week period prior to 12-week follow-up.

Other Outcomes (1)

• Number of serious and severe infusion reactions

  During infusion visit

Study Arms (2)

Intravenous Iron

EXPERIMENTAL

Participants will receive a single intravenous infusion of ferric derisomaltose (Monofer) diluted in 0.9% sodium chloride, administered at a dose up to a maximum of 20 mg/kg according to calculated iron requirement.

Drug: Ferric Derisomaltose

Placebo

PLACEBO COMPARATOR

Participants will receive a single intravenous infusion of placebo consisting of 0.9% sodium chloride administered in a volume-matched blinded infusion.

Drug: Placebo

Interventions

Placebo DRUG

Placebo consisting of 0.9% sodium chloride administered as a single volume-matched intravenous infusion.

Placebo

Ferric Derisomaltose DRUG

Ferric derisomaltose (Monofer) administered as a single intravenous infusion at a dose up to a maximum of 20 mg/kg diluted in 0.9% sodium chloride.

Intravenous Iron

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Willing and able to provide written informed consent.
• Clinical diagnosis of heart failure with preserved ejection fraction (HFpEF).
• New York Heart Association (NYHA) class II or III symptoms at the time of randomisation.
• Ambulatory for at least 7 days prior to randomisation.
• Iron deficiency defined as transferrin saturation (TSAT) \<20%.
• Haemoglobin ≤15.0 g/dL.
• Baseline 6-minute walk distance \<450 metres.

You may not qualify if:

• Unable or unwilling to provide informed consent.
• Prior documented left ventricular ejection fraction (LVEF) \<40%.
• Clinical signs or symptoms of active infection, including fever \>38°C.
• Intravenous iron therapy, erythropoietin therapy, or blood transfusion within the previous 3 months.
• Concurrent immunosuppressive therapy.
• Known iron overload syndrome or haemochromatosis, or first-degree relative with haemochromatosis.
• Known hypersensitivity to ferric derisomaltose (Monofer) or other intravenous iron preparations.
• Known bleeding anaemia or haemolytic anaemia.
• Any condition precluding exercise testing, including decompensated heart failure, unstable angina, obstructive cardiomyopathy, severe uncorrected valvular disease, significant musculoskeletal disease, or uncontrolled bradyarrhythmias or tachyarrhythmias.
• Probable alternative explanation for symptoms in the opinion of the investigator, including severe obesity, primary pulmonary hypertension, or chronic obstructive pulmonary disease (COPD).
• Severe COPD defined as FEV1 \<50%, requirement for home oxygen therapy, or chronic oral steroid therapy.
• Renal replacement therapy or estimated glomerular filtration rate (eGFR) \<15 mL/min/1.73m².
• Uncontrolled atrial fibrillation with resting heart rate \>110 beats/minute.
• Uncontrolled hypertension with blood pressure \>180/110 mmHg.
• Concurrent therapy with an erythropoiesis-stimulating agent.

Sponsors & Collaborators

• Government of Jersey: lead
• University of Oxford: collaborator

Study Sites (1)

Jersey General Hospital

Saint Helier, Jersey

Location

MeSH Terms

Conditions

Heart Failure

Interventions

ferric derisomaltose

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• John Aaron Henry

  Government of Jersey

  PRINCIPAL INVESTIGATOR

• Andrew Mitchell

  Government of Jersey

  STUDY CHAIR

• Oliver Rider

  Oxford Centre for Clinical Magnetic Resonance Research

  STUDY CHAIR

Central Study Contacts

Aaron Henry

CONTACT

01534 444267; a.henry@health.gov.je

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study will be conducted in a double-blind fashion. Ferric derisomaltose and placebo infusions will be prepared and administered by non-study clinical staff not otherwise involved in trial assessments. Infusion bags and tubing will be concealed to maintain blinding, and participants will be offered an eye mask during infusion procedures. Randomisation records will be retained separately for emergency unblinding if required.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Heart Failure Research Group Lead

Study Record Dates

• First Submitted: June 7, 2026
• First Posted: June 12, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 12, 2026

Record last verified: 2026-06

Locations

JE (1)