Heart Failure With Preserved Ejection Fraction (HFpEFPhase 2ISLE HFpEFNCT07643818
Intravenous Iron to Improve Symptoms, Quality of Life and Exercise Capacity in HFpEF With Iron Deficiency
A Phase 2 study testing Ferric Derisomaltose in people with Heart Failure With Preserved Ejection Fraction (HFpEF, run by Government of Jersey at 1 site in Jersey.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction (HFpEF
- What is being tested?
- Ferric Derisomaltose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteJersey
- Study dates
- 19 Jun 2026to Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years.
- Willing and able to provide written informed consent.
- Clinical diagnosis of heart failure with ejection fraction ≥40%.
- 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% or serum iron ≤13umol/L
- Haemoglobin ≤15.0 g/dL.
- Baseline 6-minute walk distance <450 metres.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
- Known active malignancy.
- Known HIV infection or active hepatitis infection.
- Pregnancy.
- Decompensated liver disease.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jersey1 site
Jersey General Hospital
Saint Helier
About this study
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.
Read more
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.
Read the detailed description
Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases and is associated with substantial morbidity, reduced exercise capacity, impaired quality of life, and frequent hospitalisation. Iron deficiency is highly prevalent in patients with heart failure and may be even more common in HFpEF than in heart failure with reduced ejection fraction (HFrEF). In heart failure populations, iron deficiency has been associated with impaired functional capacity, reduced quality of life, and adverse cardiovascular outcomes.
Intravenous (IV) iron therapy has demonstrated symptomatic and functional benefits in multiple randomised trials in patients with HFrEF and iron deficiency, leading to incorporation into contemporary heart failure guidelines. However, evidence supporting IV iron therapy in HFpEF remains limited. The FAIR-HFpEF trial suggested potential improvements in exercise capacity following IV iron therapy, but recruitment challenges resulted in early termination and limited statistical power. Additional adequately powered studies are therefore required to evaluate the efficacy of IV iron in HFpEF.
Iron plays a central role in mitochondrial oxidative phosphorylation and cellular energy production. Impaired myocardial energetics have been demonstrated in iron-deficient heart failure patients and may be particularly relevant in HFpEF, where diastolic relaxation is an energy-dependent process. Restoration of iron stores may therefore improve exercise tolerance, symptoms, and functional status in patients with HFpEF.
ISLE-HFpEF is a prospective, randomised, double-blind, placebo-controlled, parallel-group trial evaluating the effects of intravenous ferric derisomaltose (Monofer) in adults with symptomatic HFpEF and iron deficiency. A total of 150 participants will be randomised in a 1:1 ratio to receive either a single infusion of ferric derisomaltose (up to 20 mg/kg) or placebo (0.9% sodium chloride). Participants will undergo baseline assessment, randomisation and infusion after a two-week run-in period, and follow-up assessment 12 weeks after treatment.
The primary objective is to determine whether IV iron improves exercise capacity, assessed by change in 6-minute walk distance at 12 weeks. Secondary objectives include assessment of quality of life, symptom burden, biochemical markers, and functional status.
The study will also investigate the use of wearable technologies as digital endpoints in cardiovascular clinical trials. Participants will wear a SENS Motion thigh-worn accelerometer continuously for 12 weeks to measure habitual physical activity, including daily step count, physical activity intensity, and sedentary behaviour. Participants will additionally use the Oura Ring Generation 4 to collect exploratory physiological metrics including heart rate variability, resting heart rate, respiratory rate, activity patterns, and estimated cardiorespiratory fitness. These devices are intended to provide objective measures of real-world functional status and behavioural change that may complement traditional clinic-based assessments.
Safety assessments will include monitoring for adverse events and infusion-related hypersensitivity reactions throughout the study period.
- Being tested
- Ferric Derisomaltose, Placebo
- Keywords
- HFpEF, Iron, Heart Failure
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferric DerisomaltoseDrug
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.
PlaceboDrug
Placebo consisting of 0.9% sodium chloride administered as a single volume-matched intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 12 weeks post-treatment.
Secondary outcomes (6)
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Change in patient-reported health status and quality of life assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ Overall Summary Score ranges from 0 to 100, where 0 represents the worst possible health status and 100 represents the best possible health status. Higher scores indicate better patient-reported health status; therefore, a positive change from baseline indicates improvement.
Measured: Baseline and 12 weeks post-treatment.
Change in transferrin saturation (TSAT)
Change in transferrin saturation as a marker of iron status following treatment.
Measured: Baseline and 12 weeks post-treatment.
Change in NT-proBNP
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration following treatment.
Measured: Baseline and 12 weeks post-treatment.
Change in total daily step count
Change in average daily step count measured using the SENS Motion accelerometer, comparing the 2-week period prior to infusion with the final 2-week period prior to the 12-week follow-up visit.
Measured: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
Change in time spent in sedentary behaviour
Change in average daily time spent sedentary measured using the SENS Motion accelerometer, comparing the 2-week period prior to infusion with the final 2-week period prior to the 12-week follow-up visit.
Measured: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
Change in time spent in moderate-to-vigorous physical activity (MVPA)
Change in average daily time spent in moderate-to-vigorous physical activity (MVPA) measured using the SENS Motion accelerometer, comparing the 2-week period prior to infusion with the final 2-week period prior to the 12-week follow-up visit.
Measured: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2026
- Study start19 Jun 2026
- Primary completionJul 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection Fraction (HFpEFStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Government of Jersey
- Sponsor type
- Other government
- Collaborators
- University of Oxford
- Responsible party
- Principal investigator, Aaron Henry, Government of Jersey
- Investigators
- John Aaron Henry, Principal investigator, Government of JerseyAndrew Mitchell, Study chair, Government of JerseyOliver Rider, Study chair, Oxford Centre for Clinical Magnetic Resonance Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07643818
- Sponsor's protocol ID
- 2026HREC02
- Acronym
- ISLE HFpEF
- Status last verified
- Jun 2026
- First submitted
- 7 Jun 2026
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous Iron to Improve Symptoms, Quality of Life and Exercise Capacity in HFpEF With Iron Deficiency
- ClinicalTrials.gov ID
- NCT07643818
- Acronym / sponsor ID
- ISLE HFpEF / 2026HREC02
- Keywords
- HFpEF, Iron, Heart Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Government of JerseyOther government
- Collaborators
- University of Oxford
- Study start
- 19 Jun 2026 (actual)
- Primary completion
- Jul 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 12 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases and is associated with substantial morbidity, reduced exercise capacity, impaired quality of life, and frequent hospitalisation. Iron deficiency is highly prevalent in patients with heart failure and may be even more common in HFpEF than in heart failure with reduced ejection fraction (HFrEF). In heart failure populations, iron deficiency has been associated with impaired functional capacity, reduced quality of life, and adverse cardiovascular outcomes.
Intravenous (IV) iron therapy has demonstrated symptomatic and functional benefits in multiple randomised trials in patients with HFrEF and iron deficiency, leading to incorporation into contemporary heart failure guidelines. However, evidence supporting IV iron therapy in HFpEF remains limited. The FAIR-HFpEF trial suggested potential improvements in exercise capacity following IV iron therapy, but recruitment challenges resulted in early termination and limited statistical power. Additional adequately powered studies are therefore required to evaluate the efficacy of IV iron in HFpEF.
Iron plays a central role in mitochondrial oxidative phosphorylation and cellular energy production. Impaired myocardial energetics have been demonstrated in iron-deficient heart failure patients and may be particularly relevant in HFpEF, where diastolic relaxation is an energy-dependent process. Restoration of iron stores may therefore improve exercise tolerance, symptoms, and functional status in patients with HFpEF.
ISLE-HFpEF is a prospective, randomised, double-blind, placebo-controlled, parallel-group trial evaluating the effects of intravenous ferric derisomaltose (Monofer) in adults with symptomatic HFpEF and iron deficiency. A total of 150 participants will be randomised in a 1:1 ratio to receive either a single infusion of ferric derisomaltose (up to 20 mg/kg) or placebo (0.9% sodium chloride). Participants will undergo baseline assessment, randomisation and infusion after a two-week run-in period, and follow-up assessment 12 weeks after treatment.
The primary objective is to determine whether IV iron improves exercise capacity, assessed by change in 6-minute walk distance at 12 weeks. Secondary objectives include assessment of quality of life, symptom burden, biochemical markers, and functional status.
The study will also investigate the use of wearable technologies as digital endpoints in cardiovascular clinical trials. Participants will wear a SENS Motion thigh-worn accelerometer continuously for 12 weeks to measure habitual physical activity, including daily step count, physical activity intensity, and sedentary behaviour. Participants will additionally use the Oura Ring Generation 4 to collect exploratory physiological metrics including heart rate variability, resting heart rate, respiratory rate, activity patterns, and estimated cardiorespiratory fitness. These devices are intended to provide objective measures of real-world functional status and behavioural change that may complement traditional clinic-based assessments.
Safety assessments will include monitoring for adverse events and infusion-related hypersensitivity reactions throughout the study period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous Iron | Experimental | Drug: Ferric DerisomaltoseParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive a single intravenous infusion of placebo consisting of 0.9% sodium chloride administered in a volume-matched blinded infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥18 years.
- Willing and able to provide written informed consent.
- Clinical diagnosis of heart failure with ejection fraction ≥40%.
- New York Heart Association (NYHA) class II or III symptoms at the time of randomisation.
- Ambulatory for at least 7 days prior to randomisation.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ferric DerisomaltoseFerric 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. | Drug | Intravenous Iron |
| PlaceboPlacebo consisting of 0.9% sodium chloride administered as a single volume-matched intravenous infusion. | Drug | Placebo |
Primary outcome
Change in 6-minute walk distance (6MWD)
Time frame: Baseline and 12 weeks post-treatment.
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.
6 secondary outcomes
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Time frame: Baseline and 12 weeks post-treatment.
Change in transferrin saturation (TSAT)
Time frame: Baseline and 12 weeks post-treatment.
Change in NT-proBNP
Time frame: Baseline and 12 weeks post-treatment.
Change in total daily step count
Time frame: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
Change in time spent in sedentary behaviour
Time frame: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
Change in time spent in moderate-to-vigorous physical activity (MVPA)
Time frame: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
John Aaron Henry principal investigator
Government of Jersey
Andrew Mitchell study chair
Government of Jersey
Oliver Rider study chair
Oxford Centre for Clinical Magnetic Resonance Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ferric Derisomaltose in people with Heart Failure With Preserved Ejection Fraction (HFpEF, run by Government of Jersey at 1 site in Jersey.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Jersey. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in 6-minute walk distance (6MWD) (time frame: Baseline and 12 weeks post-treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.