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.
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 장소
-
-
-
Saint Helier, 저지
- Jersey General Hospital
-
-
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 더블
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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.
|
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.
|
|
위약 비교기: Placebo
Participants will receive a single intravenous infusion of placebo consisting of 0.9% sodium chloride administered in a volume-matched blinded infusion.
|
Placebo consisting of 0.9% sodium chloride administered as a single volume-matched intravenous infusion.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change in 6-minute walk distance (6MWD)
기간: 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.
|
Baseline and 12 weeks post-treatment.
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change in transferrin saturation (TSAT)
기간: Baseline and 12 weeks post-treatment.
|
Change in transferrin saturation as a marker of iron status following treatment.
|
Baseline and 12 weeks post-treatment.
|
|
Change in NT-proBNP
기간: Baseline and 12 weeks post-treatment.
|
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration following treatment.
|
Baseline and 12 weeks post-treatment.
|
|
Change in total daily step count
기간: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
|
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.
|
Baseline 2-week period and final 2-week period prior to 12-week follow-up.
|
|
Change in time spent in sedentary behaviour
기간: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
|
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.
|
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)
기간: Baseline 2-week period and final 2-week period prior to 12-week follow-up.
|
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.
|
Baseline 2-week period and final 2-week period prior to 12-week follow-up.
|
|
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
기간: Baseline and 12 weeks post-treatment.
|
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.
|
Baseline and 12 weeks post-treatment.
|
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Number of serious and severe infusion reactions
기간: During infusion visit
|
Number of serious and severe infusion reactions (Medical Dictionary for Regulatory Activities Anaphylactic Reaction SMQ (groups A, B, C, or D))
|
During infusion visit
|
공동 작업자 및 조사자
수사관
- 수석 연구원: John Aaron Henry, Government of Jersey
- 연구 의자: Andrew Mitchell, Government of Jersey
- 연구 의자: Oliver Rider, Oxford Centre for Clinical Magnetic Resonance Research
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .