Intravenous Iron to Improve Symptoms, Quality of Life and Exercise Capacity in HFpEF With Iron Deficiency (ISLE HFpEF)
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.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Saint Helier, Camisa
- Jersey General Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Known active malignancy.
- Known HIV infection or active hepatitis infection.
- Pregnancy.
- Decompensated liver disease.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Intravenous Iron
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.
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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.
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Comparador de Placebo: Placebo
Participants will receive a single intravenous infusion of placebo consisting of 0.9% sodium chloride administered in a volume-matched blinded infusion.
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Placebo consisting of 0.9% sodium chloride administered as a single volume-matched intravenous infusion.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change in 6-minute walk distance (6MWD)
Prazo: Baseline and 12 weeks post-treatment.
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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.
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Baseline and 12 weeks post-treatment.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change in transferrin saturation (TSAT)
Prazo: Baseline and 12 weeks post-treatment.
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Change in transferrin saturation as a marker of iron status following treatment.
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Baseline and 12 weeks post-treatment.
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Change in NT-proBNP
Prazo: Baseline and 12 weeks post-treatment.
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Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration following treatment.
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Baseline and 12 weeks post-treatment.
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Change in total daily step count
Prazo: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
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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.
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Baseline 2-week period and final 2-week period prior to 12-week follow-up.
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Change in time spent in sedentary behaviour
Prazo: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
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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.
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Baseline 2-week period and final 2-week period prior to 12-week follow-up.
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Change in time spent in moderate-to-vigorous physical activity (MVPA)
Prazo: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
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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.
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Baseline 2-week period and final 2-week period prior to 12-week follow-up.
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Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Prazo: Baseline and 12 weeks post-treatment.
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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.
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Baseline and 12 weeks post-treatment.
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
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Number of serious and severe infusion reactions
Prazo: During infusion visit
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Number of serious and severe infusion reactions (Medical Dictionary for Regulatory Activities Anaphylactic Reaction SMQ (groups A, B, C, or D))
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During infusion visit
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: John Aaron Henry, Government of Jersey
- Cadeira de estudo: Andrew Mitchell, Government of Jersey
- Cadeira de estudo: Oliver Rider, Oxford Centre for Clinical Magnetic Resonance Research
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 2026HREC02
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