Intravenous iron treatment in patients with heart failure and iron deficiency: IRONMAN
| ISRCTN | ISRCTN16403302 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16403302 |
| EudraCT/CTIS number | 2015-004196-73 |
| ClinicalTrials.gov number | NCT02642562 |
| Secondary identifying numbers | 31982 |
- Submission date
- 28/11/2016
- Registration date
- 15/12/2016
- Last edited
- 08/09/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English Summary
Current plain English summary as of 16/03/2022:
Background and study aims
Chronic heart failure (CHF) is a long-term condition where the heart has become weakened and isn’t able to pump blood around the body effectively. Chronic heart failure (CHF) is a very common problem. Despite improvements in treatment, many patients suffer limiting symptoms of shortness of breath and fatigue (extreme tiredness). Many patients with CHF have iron deficiency, meaning that the iron levels in their blood are too low or they are unable to utilise iron properly. This is associated with poor health outcomes, as iron is vital for the transport of oxygen around the body by red blood cells. The aim of this study is to find out whether treating iron-deficient CHF patients with intravenous (through a vein) iron is an effective way of reducing death due to circulatory system problems, and hospitalisation due to heart failure.
Who can participate?
Adults with chronic heart failure and iron deficiency.
What does the study involve?
Participants are randomly allocated to one of two groups. On the formal study visit, those in the first group receive iron through a trip at an individual dosage calculated from their height, weight and current iron levels. This takes around 15-30 minutes and participants need to stay in the clinic for around 30 minutes before going home. The whole visit takes between 1.5-2 hours. Those in the second group do not receive any iron and have blood tests at the formal study visit only. This takes between 1-1.5 hours. For those in both groups, subsequent study visits are arranged at 4 weeks and then three times a year for the rest of the study (between 3 months and 5.5 years). At these follow-up visits, participants undergo a clinical assessment (including checking weight, blood pressure and pulse) and are asked about their symptoms, medication and any medical problems since the last visit as well as completing a quality of life questionnaire.
What are the possible benefits and risks of participating?
If the iron treatment is successful and iron deficiency improves or is completely resolved, participants may feel better. There is no guarantee that a benefit will be felt by participants, however. Nevertheless, results from this study may provide information which will help us to treat heart failure patients with iron deficiency more successfully in the future. Participants may experience side effects related to the iron therapy but these are rare. Initial screening tests may reveal a medical problem which may mean the participant can’t be entered into the study. Blood sampling is a part of this study and may cause minor discomfort and bruising.
Where is the study run from?
Queen Alexandra Hospital (lead site) and around 64 other NHS hospitals (UK)
When is the study starting and how long is it expected to run for?
July 2015 to August 2022
Who is funding the study?
1. British Heart Foundation (UK)
2. Pharmacosmos UK Ltd. (UK)
Who is the main contact?
Ms Elizabeth Thomson
elizabeth.thomson@glasgow.ac.uk
_____
Previous plain English summary:
Background and study aims
Chronic heart failure (CHF) is a long-term condition where the heart has become weakened and isn’t able to pump blood around the body effectively. Chronic heart failure (CHF) is a very common problem. Despite improvements in treatment, many patients suffer limiting symptoms of shortness of breath and fatigue (extreme tiredness). Many patients with CHF have iron deficiency, meaning that the iron levels in their blood are too low or they are unable to utilise iron properly. This is associated with poor health outcomes, as iron is vital for the transport of oxygen around the body by red blood cells. The aim of this study is to find out whether treating iron-deficient CHF patients with intravenous (through a vein) iron is an effective way of reducing death due to circulatory system problems, and hospitalisation due to heart failure.
Who can participate?
Adults with chronic heart failure and iron deficiency.
What does the study involve?
Participants are randomly allocated to one of two groups. On the formal study visit, those in the first group receive iron through a trip at an individual dosage calculated from their height, weight and current iron levels. This takes around 15-30 minutes and participants need to stay in the clinic for around 30 minutes before going home. The whole visit takes between 1.5-2 hours. Those in the second group do not receive any iron and have blood tests at the formal study visit only. This takes between 1-1.5 hours. For those in both groups, subsequent study visits are arranged at 4 weeks and then three times a year for the rest of the study (between 2.5 and 4.5 years). At these follow up visits, participants undergo a clinical assessment (including checking weight, blood pressure and pulse) and are asked about their symptoms, medication and any medical problems since the last visit as well as completing a quality of life questionnaire.
What are the possible benefits and risks of participating?
If the iron treatment is successful and iron deficiency improves or is completely resolved, participants may feel better. There is no guarantee that a benefit will be felt by participants, however. Nevertheless, results from this study may provide information which will help us to treat heart failure patients with iron deficiency more successfully in the future. Participants may experience side effects related to the iron therapy but these are rare. Initial screening tests may reveal a medical problem which may mean the participant can’t be entered into the study. Blood sampling is a part of this study and may cause minor discomfort and bruising.
Where is the study run from?
Queen Alexandra Hospital (lead site) and around 64 other NHS hospitals (UK)
When is the study starting and how long is it expected to run for?
July 2015 to March 2022
Who is funding the study?
1. British Heart Foundation (UK)
2. Pharmacosmos UK Ltd. (UK)
Who is the main contact?
Ms Elizabeth Thomson
elizabeth.thomson@glasgow.ac.uk
Contact information
Public
Institute of Health and Wellbeing
College of Medical, Veterinary and Life Sciences
Robertson Centre for Biostatistics
University of Glasgow
Boyd Orr Building, Level 11
Glasgow
G12 8QQ
United Kingdom
| Phone | +44 (0)141 330 4744 |
|---|---|
| elizabeth.thomson@glasgow.ac.uk |
Study information
| Study design | Randomized interventional |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Effectiveness of intravenous iron treatment vs standard care in patients with heart failure and iron deficiency: a randomised, open-label multicentre trial (IRONMAN) |
| Study acronym | IRONMAN |
| Study hypothesis | The aim of this study is to establish in patients with chronic heart failure and iron deficiency whether treatment with intravenous iron is effective in reducing death due to cardiovascular problems, and hospitalisation due to heart failure. |
| Ethics approval(s) | East Midlands - Leicester South Research Ethics Committee, 25/02/2016, ref: 15/EM/0551 |
| Condition | Heart failure and iron deficiency |
| Intervention | Current intervention as of 16/03/2022: Participants are randomised to one of two groups. All participants will be involved in the study for an average approximately 4 years (event driven trial, expected maximum around 5.5 years, minimum around 3 months – anticipated 5 years recruitment and a projected further minimum 3 months of treatments/assessments, giving a range of projected patient participation of around 3 months – 5.5 years). All participants will be seen at 4 weeks and then every 4 months for study duration. Intervention arm: Participants will receive an injection at the first formal study visit. The iron (ferric derisomaltose) is given intravenously as an infusion over 15-30 minutes and the dosage that is required is calculated according to participant weight and blood tests (calculated by electronic case record form, eCRF). The participant will then need to stay in the clinic for another 30 minutes before going home. This whole visit will take around 1.5 to 2 hours. Subsequent study visits will be arranged at around 4 weeks and then every 4 months (that is three times a year) until the study finishes. Blood will be tested at, or before, each study visit. At each visit there will be a clinical assessment (including checking weight, blood pressure, pulse) and the research team will ask about symptoms, medication and any medical problems since the last visit. A quality of life questionnaire will be completed (a second questionnaire and a walking test for 6 minutes will be offered at two further time points during the study). Each visit will last around 1 hour. An iron infusion will only be required if iron levels are found to be low; on average we expect this to be around once a year (this will vary between participants – some needing it more often and others less often). The iron injection (Monofer®) will normally be given at a separate appointment although it may sometimes be possible for this to be given on the same day as the study visit. It is anticipated that participants will be in the clinic for around 1.5 to 2 hours for each iron injection. Standard arm: Participants will not receive the intervention (intravenous iron). Blood will be tested at the formal study visit. This visit will take approximately 1 – 1.5 hours. Subsequent study visits will be arranged at convenient times at around 4 weeks and then every 4 months (that is three times a year) until the study finishes. Blood will be tested at, or before, each study visit. At each visit there will be a clinical assessment (including checking weight, blood pressure, pulse) and the research team will ask about symptoms, medication and any medical problems since the last visit. A quality of life questionnaire will be completed (a second questionnaire and a walking test for 6 minutes will be offered at two further time points during the study). Each visit will last around 1 hour. _____ Previous intervention: Participants are randomised to one of two groups. All participants will be involved in the study for an average of 3 years (event driven trial, expected maximum 4.5 years, minimum 2.5 years – anticipated 2 years recruitment and a projected further 2 years of treatments/assessments, and a further closeout visit giving a range of projected patient participation of 2.5 – 4.5 years). All participants will be seen at 4 weeks and then every 4 months for study duration. Intervention arm: Participants will receive an injection at the first formal study visit. The iron (iron isomaltoside 1000) is given intravenously as an infusion over 15-30 minutes and the dosage that is required is calculated according to participant weight and blood tests (calculated by electronic case record form, eCRF). The participant will then need to stay in the clinic for another 30 minutes before going home. This whole visit will take around 1.5 to 2 hours. Subsequent study visits will be arranged at around 4 weeks and then every 4 months (that is three times a year) until the study finishes. Blood will be tested at, or before, each study visit. At each visit there will be a clinical assessment (including checking weight, blood pressure, pulse) and the research team will ask about symptoms, medication and any medical problems since the last visit. A quality of life questionnaire will be completed (a second questionnaire and a walking test for 6 minutes will be offered at two further time points during the study). Each visit will last around 1 hour. An iron infusion will only be required if iron levels are found to be low; on average we expect this to be around once a year (this will vary between participants – some needing it more often and others less often). The iron injection (Monofer®) will normally be given at a separate appointment although it may sometimes be possible for this to be given on the same day as the study visit. It is anticipated that participants will be in the clinic for around 1.5 to 2 hours for each iron injection. Standard arm: Participants will not receive the intervention (intravenous iron). Blood will be tested at the formal study visit. This visit will take approximately 1 – 1.5 hours. Subsequent study visits will be arranged at convenient times at around 4 weeks and then every 4 months (that is three times a year) until the study finishes. Blood will be tested at, or before, each study visit. At each visit there will be a clinical assessment (including checking weight, blood pressure, pulse) and the research team will ask about symptoms, medication and any medical problems since the last visit. A quality of life questionnaire will be completed (a second questionnaire and a walking test for 6 minutes will be offered at two further time points during the study). Each visit will last around 1 hour. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Monofer (ferric derisomaltose/iron isomaltoside 1000) |
| Primary outcome measure | Current primary outcome measure as of 07/09/2022: CV mortality or hospitalisation for worsening heart failure is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow-up period (minimum of 3 months follow-up from last patient recruited) _____ Previous primary outcome measure as of 16/03/2022: Cardiovascular CV mortality or hospitalisation for worsening heart failure is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 3 months - 5.5 years or 4 years on average) _____ Previous primary outcome measure: Cardiovascular CV mortality or hospitalisation for worsening heart failure is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average). |
| Secondary outcome measures | Current secondary outcome measures as of 07/09/2022: 1. Hospitalisation for worsening heart failure (recurrent events) [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] 2. CV hospitalisation (first event) [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] 3. CV death or hospitalisation for heart failure analysed as time to first event [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] 4. Overall Score from Minnesota Living with Heart Failure [ Time Frame: At 4 months ] 5. Cardiovascular mortality [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] 6. Overall EQ-5D VAS [ Time Frame: At 4 months ] 7. Overall EQ-5D index [ Time Frame: At 4 months ] 8. CV mortality or hospitalisation for major CV event (stroke, MI, heart failure) (first event) [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] 9. All-cause mortality [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] 10. All-cause hospitalisation (first event) [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] 11. Combined all-cause mortality or first all-cause unplanned hospitalisation [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] 12. Physical domain of QoL (Minnesota Living With Heart Failure) [ Time Frame: At 4 months ] 13. Physical domain of QoL (Minnesota Living With Heart Failure) [ Time Frame: At 20 months ] 14. Overall EQ-5D VAS [ Time Frame: At 20 months ] 15. Overall EQ-5D index [ Time Frame: At 20 months ] 16. Overall Score from Minnesota Living With Heart Failure [ Time Frame: At 20 months ] 17. Days dead or hospitalised [ Time Frame: At 36 months ] 18. Quality-adjusted days alive and out of hospital [ Time Frame: At 12 months ] 19. 6 minute walk test [ Time Frame: At 4 months ] 20. 6 minute walk test [ Time Frame: At 20 months ] 21. Death due to infection [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] 22. Hospitalisation primarily for infection (first event) [ Time Frame: Minimum of 3 months follow-up from last patient recruited ] _____ Previous secondary outcome measures as of 16/03/2022: 1. CV mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 3 months - 5.5 years or 4 years on average) 2. Hospitalisation for worsening heart failure (analysis will include first and recurrent hospitalisations) and is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 3 months - 5.5 years or 4 years on average) 3. All-cause mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 3 months - 5.5 years or 4 years on average) 4. CV mortality or first hospitalisation for major CV event (stroke, myocardial infarction [MI], heart failure). Days dead or hospitalised is assessed through review of case notes and reporting of patient, relative, carer or clinician 5. Physical domain of QoL (Minnesota Living With Heart Failure) – this will be the difference between groups at 4 months and also at 20 months. Minnesota Living with Heart Failure is used at these time points to measure QoL. 6. Overall QoL assessment (Minnesota Living With Heart Failure, EQ-5D index and EQ-5D VAS) – this will be the difference between groups at 4 months and also at 20 months. Minnesota Living with Heart Failure and EQ-5D are used at these time points to measure QoL. 7. Combined all-cause mortality or first all-cause unplanned hospitalization is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 3 months - 5.5 years or 4 years on average) 8. Days dead or hospitalised at 3 years (minimum duration of follow-up) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period 9. Quality-adjusted days alive and out of hospital at 3 years assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period 10. CV hospitalisation (first event) assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 3 months - 5.5 years or 4 years on average) 11. All-cause hospitalisation (first event) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 3 months - 5.5 years or 4 years on average) 12. 6-minute walk test - this will be the difference between groups at 4 months and also at 20 months. 13. (Secondary safety) Death due to infection is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 3 months - 5.5 years or 4 years on average) 14. (Secondary safety) Hospitalisation primarily for infection is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 3 months - 5.5 years or 4 years on average) _____ Previous secondary outcome measures as of 31/12/2019: 1. CV mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 2. Hospitalisation for worsening heart failure (analysis will include first and recurrent hospitalisations) and is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 3. All-cause mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 4. CV mortality or first hospitalisation for major CV event (stroke, myocardial infarction [MI], heart failure). Days dead or hospitalised is assessed through review of case notes and reporting of patient, relative, carer or clinician at 2.5 years of follow up. 5. Physical domain of QoL (Minnesota Living With Heart Failure) – this will be the difference between groups at 4 months and also at 20 months. Minnesota Living with Heart Failure is used at these time points to measure QoL. 6. Overall QoL assessment (Minnesota Living With Heart Failure, EQ-5D index and EQ-5D VAS) – this will be the difference between groups at 4 months and also at 20 months. Minnesota Living with Heart Failure and EQ-5D are used at these time points to measure QoL. 7. Combined all-cause mortality or first all-cause unplanned hospitalization is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 8. Days dead or hospitalised at 2.5 years (minimum duration of follow-up) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 9. Quality-adjusted days alive and out of hospital at 2.5 years ) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 10. CV hospitalisation (first event) ) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 11. All-cause hospitalisation (first event) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 12. 6-minute walk test - this will be the difference between groups at 4 months and also at 20 months. 13. Death due to infection is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 14. Hospitalisation primarily for infection is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) _____ Previous secondary outcome measures as of 31/05/2018: 1. CV mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 2. Hospitalisation for worsening heart failure (analysis will include first and recurrent hospitalisations) and is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 3. All-cause mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 4. CV mortality or first hospitalisation for major CV event (stroke, myocardial infarction [MI], heart failure). Days dead or hospitalised is assessed through review of case notes and reporting of patient, relative, carer or clinician at 2.5 years of follow up. 5. Physical domain of QoL (Minnesota Living With Heart Failure) – this will be the difference between groups at 4 months and also at 20 months. Minnesota Living with Heart Failure is used at these time points to measure QoL. 6. Overall QoL assessment (Minnesota Living With Heart Failure, EQ-5D index and EQ-5D VAS) – this will be the difference between groups at 4 months and also at 20 months. Minnesota Living with Heart Failure and EQ-5D are used at these time points to measure QoL. 7. Combined all-cause mortality or first all-cause unplanned hospitalization is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 8. Days dead or hospitalised at 2.5 years (minimum duration of follow-up) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 9. Quality-adjusted days alive and out of hospital at 2.5 years ) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 10. CV hospitalisation (first event) ) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 11. All-cause hospitalisation (first event) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 12. 6-minute walk test - this will be the difference between groups at 4 months and also at 20 months. 13. Death due to sepsis is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 14. Hospitalisation primarily for infection is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) _____ Previous secondary outcome measures: 1. CV mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 2. Hospitalisation for worsening heart failure (analysis will include first and recurrent hospitalisations) and is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 3. All-cause mortality is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 4. CV mortality or first hospitalisation for major CV event (stroke, myocardial infarction [MI], heart failure). Days dead or hospitalised is assessed through review of case notes and reporting of patient, relative, carer or clinician at 2.5 years of follow up. 5. Physical domain of Quality of Life (QoL) - this will be the difference between groups at 4 months and also at 20 months. Minnesota Living with Heart Failure and EQ-5D are used at these time points to measure QoL. 6. Overall QoL assessment - this will be the difference between groups at 4 months and also at 20 months Minnesota Living with Heart Failure and EQ-5D are used at these time points to measure QoL. 7. Combined all-cause mortality or first all-cause unplanned hospitalization is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 8. Days dead or hospitalised at 2.5 years (minimum duration of follow-up) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 9. Quality-adjusted days alive and out of hospital at 2.5 years ) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 10. CV hospitalisation (first event) ) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 11. All-cause hospitalisation (first event) is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 12. Death due to sepsis is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) 13. Hospitalisation primarily for infection is assessed through review of case notes and reporting of patient, relative, carer or clinician throughout the follow up period (range 2.5 – 4.5 years or 3 years on average) |
| Overall study start date | 08/07/2015 |
| Overall study end date | 31/08/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 1300; UK Sample Size: 1300 |
| Total final enrolment | 1137 |
| Participant inclusion criteria | Current inclusion criteria as of 31/05/2018: 1. Aged ≥18 years 2. LVEF <45% within the prior two years using any conventional imaging modality (this should be the most recent assessment of LVEF) 3. New York Heart Association (NYHA) class II – IV 4. Iron deficient - defined as TSAT <20% and/or ferritin <100 mcg/l 5. Evidence of being in a higher risk HF group: 5.1. Current (with the expectation that patient will survive to discharge) or recent (within 6 months) hospitalisation for HF (as of 08/10/2018), or 5.2. Out-patients with NT-proBNP >250 ng/l in sinus rhythm or >1,000 ng/l in atrial fibrillation (or BNP of >75 pg/ml or 300 pg/ml, respectively) 6. Able and willing to provide informed consent Previous inclusion criteria: 1. Age ≥18 years 2. LVEF <45% within the last 6 months using any conventional imaging modality 3. New York Heart Association (NYHA) class II – IV 4. Iron deficient defined as a TSAT<20% and/or ferritin >100 mcg/l 5. Evidence of being in a higher risk heart failure group: 5.1. Current (with intention to discharge in next 48 hours) or recent (within 6 months) hospitalisation for heart failure, or 5.2. Outpatients with NTproBNP >250 ng/l in sinus rhythm or >1,000 ng/l in atrial fibrillation (or BNP of > 75 pg/ml or 300 pg/ml, respectively) 6. Able and willing to provide informed consent |
| Participant exclusion criteria | Current exclusion criteria as of 31/12/2019: 1. Haematological criteria: ferritin >400ug/l; haemoglobin <9.0, or >13 g/dl in women or >14 g/dl in men; (B12 or folate deficiency should be corrected but do not exclude the patient) 2. MDRD/CKD-EPI estimated glomerular filtration rate (eGFR) <15ml/min/1.73m² 3. Already planned to receive IV iron 4. Likely to need or already receiving erythropoiesis stimulating agents (ESA) 5. Any of the following apply: 5.1. Planned cardiac surgery or revascularisation 5.2. Within 3 months of any of the following: a primary diagnosis of type 1 myocardial infarction (excluding small troponin elevations in the context of heart failure admissions), cerebrovascular accident (CVA), major CV surgery or percutaneous coronary intervention (PCI), or blood transfusion 5.3. On active cardiac transplant list 5.4. Left ventricular assist device implanted 6. Any of the following comorbidities: active infection (if the patient is suffering from a significant ongoing infection as judged by the investigator recruitment should be postponed until the infection has passed or is controlled by antibiotics), other disease with life expectancy of <2 years, active clinically relevant bleeding in the investigator’s opinion, known or suspected gastro-intestinal malignancy 7. Pregnancy, women of childbearing potential (i.e. continuing menstrual cycle) not using effective contraception or breast-feeding women 8. Contraindication to IV iron in the investigator’s opinion according to current approved Summary of Product Characteristics: 8.1. Hypersensitivity to the active substance, to Monofer® or any of its excipients (water for injections, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment)) 8.2. Known serious hypersensitivity to other parenteral iron products 8.3. Non-iron deficiency anaemia (e.g. haemolytic anaemia) 8.4. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis, haemosiderosis) 8.5. Decompensated liver disease 9. Participation in another intervention study involving a drug or device within the past 90 days (co-enrolment in observational studies is permitted) ______ Previous exclusion criteria as of 08/10/2018: 1. Haematological criteria: ferritin >400ug/l; haemoglobin <9.0, or >13 g/dl in women or >14 g/dl in men; (B12 or folate deficiency should be corrected but do not exclude the patient) 2. MDRD estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2 3. Already planned to receive IV iron 4. Likely to need or already receiving erythropoiesis stimulating agents (ESA) 5. Any of the following apply: 5.1. Planned cardiac surgery or revascularisation 5.2. Within 3 months of any of the following: a primary diagnosis of type 1 myocardial infarction (excluding small troponin elevations in the context of heart failure admissions), cerebrovascular accident (CVA), major CV surgery or percutaneous coronary intervention (PCI), or blood transfusion 5.3. On active cardiac transplant list 5.4. Left ventricular assist device implanted 6. Any of the following comorbidities: active infection (if the patient is suffering from a significant ongoing infection as judged by the investigator recruitment should be postponed until the infection has passed or is controlled by antibiotics), other disease with life expectancy of <2 years, active clinically relevant bleeding in the investigator’s opinion, known or suspected gastro-intestinal malignancy 7. Pregnancy, women of childbearing potential (i.e. continuing menstrual cycle) not using effective contraception or breast-feeding women 8. Contraindication to IV iron in the investigator’s opinion according to current approved Summary of Product Characteristics: 8.1. Hypersensitivity to the active substance, to Monofer® or any of its excipients (water for injections, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment)) 8.2. Known serious hypersensitivity to other parenteral iron products 8.3. Non-iron deficiency anaemia (e.g. haemolytic anaemia) 8.4. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis, haemosiderosis) 8.5. Decompensated liver disease 9. Participation in another intervention study involving a drug or device within the past 90 days (co-enrolment in observational studies is permitted) _____ Previous exclusion criteria (as of 31/05/2018): 1. Haematological criteria: ferritin >400ug/l; haemoglobin <9.0, or >13 g/dl in women or >14 g/dl in men; (B12 or folate deficiency should be corrected but do not exclude the patient) 2. MDRD estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2 3. Chronic defined need for IV iron therapy 4. Likely to need or already receiving erythropoiesis stimulating agents (ESA) 5. Any of the following apply: (a) planned cardiac surgery or revascularisation or cardiac device implantation; (b) within 3 months of any of the following: a primary diagnosis of type 1 myocardial infarction (excluding small troponin elevations in the context of heart failure admissions), cerebrovascular accident (CVA), major CV surgery or percutaneous coronary intervention (PCI), or blood transfusion; (c) on active cardiac transplant list; (d) left ventricular assist device implanted. 6. Any of the following comorbidities: active infection (if the patient is suffering from a significant ongoing infection as judged by the investigator recruitment should be postponed until the infection has passed or is controlled by antibiotics), other disease with life expectancy of <2 years, active clinically relevant bleeding in the investigator’s opinion, known or suspected gastro-intestinal malignancy 7. Pregnancy, women of childbearing potential (i.e. continuing menstrual cycle) not using effective contraception or breast-feeding women 8. Contra-indication to IV iron in the investigator’s opinion according to current approved Summary of Product Characteristics: hypersensitivity to the active substance, to Monofer® or any of its excipients (water for injections, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment)); known serious hypersensitivity to other parenteral iron products; non-iron deficiency anaemia (e.g. haemolytic anaemia); iron overload or disturbances in utilisation of iron (e.g. haemochromatosis, haemosiderosis); decompensated liver cirrhosis and hepatitis 9. Participation in another intervention study involving a drug or device within the past 90 days (co-enrolment in observational studies is permitted) Previous exclusion criteria: 1. Haematological criteria: ferritin >400ug/L; haemoglobin <9.0 or >13 g/dL in women or >14g/dL in men; (B12 or folate deficiency should be corrected but do not exclude the patient) 2. MDRD estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2 3. Chronic defined need for IV iron therapy 4. Likely to need or already receiving erythropoiesis stimulating agents (ESA) 5. Planned cardiac surgery or revascularisation or cardiac device implantation; within 3 months of a primary diagnosis of type 1 myocardial infarction (excluding small troponin elevations in the context of heart failure admissions), cerebrovascular accident (CVA), major CV surgery or percutaneous coronary intervention (PCI), cardiac device implantation or blood transfusion; on active cardiac transplant list; left ventricular assist device implanted 6. Any of the following comorbidities: active infection (if the patient is suffering from a significant ongoing infection as judged by the investigator recruitment should be postponed until the infection has passed or is controlled by antibiotics), other disease with life expectancy of <2 years, active clinically relevant bleeding in the investigators opinion, known or suspected gastrointestinal malignancy 7. Pregnancy or women of childbearing potential (i.e. continuing menstrual cycle) not using effective contraception 8. Contraindication to IV iron in the investigator’s opinion according to current approved Summary of Product Characteristics: hypersensitivity to the active substance, to Monofer® or any of its excipients (water for injections, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment)); known serious hypersensitivity to other parenteral iron products; noniron deficiency anaemia (e.g. haemolytic anaemia); iron overload or disturbances in utilisation of iron (e.g. haemochromatosis, haemosiderosis); decompensated liver cirrhosis and hepatitis 9. Participation in another intervention study involving a drug or device within the past 90 days (coenrolment In observational studies is permitted) |
| Recruitment start date | 25/08/2016 |
| Recruitment end date | 15/10/2021 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Southwick Hill Road
Cosham
Portsmouth
PO6 3LY
United Kingdom
Glasgow
G4 0ET
United Kingdom
Clydebank
G81 4DY
United Kingdom
Govan
Glasgow
G51 4TF
United Kingdom
Salford
M6 8HD
United Kingdom
Clinical Science Wing
Leicester
LE3 9QP
United Kingdom
Brighton
BN2 5BE
United Kingdom
Swindon
SN3 6BB
United Kingdom
Mailbox 2
Dundee
DD1 9SY
United Kingdom
Basingstoke
RG24 9NA
United Kingdom
Inverness
IV2 3UJ
United Kingdom
Liverpool
L9 7AL
United Kingdom
Llantrisant
CF72 8XR
United Kingdom
Isleworth
TW7 6AF
United Kingdom
Manchester
M13 9WL
United Kingdom
Paisley
PA2 9PN
United Kingdom
London
EC1A 7BE
United Kingdom
Bloomsbury
London
NW1 2BU
United Kingdom
Cottingham
HU16 5JQ
United Kingdom
Airdrie
ML6 0JS
United Kingdom
Edinburgh
EH16 4SA
United Kingdom
Liverpool
L14 3PE
United Kingdom
Bournemouth
BH7 7DW
United Kingdom
Foresterhill Rd
Aberdeen
AB25 2ZN
United Kingdom
Exeter
EX2 5DW
United Kingdom
Coventry
CV2 2DX
United Kingdom
London
SE5 9RS
United Kingdom
Morriston
Cwmrhydyceirw
Swansea
SA6 6NL
United Kingdom
Crosshouse
Kilmarnock
KA2 0BE
United Kingdom
Wythenshawe
Manchester
M23 9LT
United Kingdom
Harefield
Uxbridge
UB9 6JH
United Kingdom
Dundonald
Belfast
BT16 1RH
United Kingdom
Eastbourne
BN21 2UD
United Kingdom
London
N18 1QX
United Kingdom
Newport
NP20 2UB
United Kingdom
Llandough
Penarth
CF64 2XX
United Kingdom
Southampton
SO16 6YD
United Kingdom
Barnet
EN5 3DJ
United Kingdom
Antrim
BT41 2RL
United Kingdom
Blackpool
FY3 8NR
United Kingdom
Bradford
BD9 6RJ
United Kingdom
Calow
Chesterfield
S44 5BL
United Kingdom
Darlington
DL3 6HX
United Kingdom
Larbert
FK5 4WR
United Kingdom
White City
London
W12 0HS
United Kingdom
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Poole
BH15 2JB
United Kingdom
Sheffield
S5 7AU
United Kingdom
Westcliff-on-Sea
SS0 0RY
United Kingdom
Ashington
NE63 9JJ
United Kingdom
High Wycombe
HP11 2TT
United Kingdom
Sunderland
SR4 7TP
United Kingdom
Torquay
TQ2 7AA
United Kingdom
East Grinstead
RH19 3DZ
United Kingdom
Lambeth
London
SE1 7EH
United Kingdom
Doncaster
DN2 5LT
United Kingdom
Stoke-on-Trent
ST4 6QG
United Kingdom
Tooting
London
SW17 0QT
United Kingdom
Broomfield
Chelmsford
CM1 7ET
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Salisbury
SP2 8BJ
United Kingdom
Kingston upon Thames
KT2 7QB
United Kingdom
Oldham
OL1 2JH
United Kingdom
Basildon
SS16 5NL
United Kingdom
Watford
WD18 0HB
United Kingdom
Chichester
PO19 6SE
United Kingdom
Bridgend
CF31 1RQ
United Kingdom
Bristol
BS2 8HW
United Kingdom
Truro
TR1 3LQ
United Kingdom
East Kilbride
G75 8RG
United Kingdom
Dumfries
Dumfries and Galloway
DG1 4AP
United Kingdom
Grainger Drive
Apley
Telford
TF1 6TF
United Kingdom
Kings Lynn
PE30 4ET
United Kingdom
530 London Road
Thornton Heath
CR7 7YE
United Kingdom
Ayr
KA6 6DX
United Kingdom
Sponsor information
University/education
University Avenue
Glasgow
G12 8QQ
Scotland
United Kingdom
| Phone | +44 141 232 1798 |
|---|---|
| Debra.Stuart@glasgow.ac.uk |
Hospital/treatment centre
R&D Management Office
Clinical Research & Development
NHS Greater Glasgow & Clyde
Ward 11, Dykebar Hospital
Grahamston Road
Paisley
PA2 7DE
Scotland
United Kingdom
| Phone | +44 (0)141 232 1813 |
|---|---|
| maureen.travers@ggc.scot.nhs.uk |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- the_bhf, The British Heart Foundation, BHF
- Location
- United Kingdom
No information available
Results and Publications
| Intention to publish date | 31/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Current publication and dissemination plan as of 07/09/2022: The study protocol and a description of the recruitment experience and participant baseline characteristics will be published before study completion. On completion of the trial, the database will be locked and analysed by the staff of the Robertson Centre for Biostatistics, University of Glasgow. A final study report will be prepared and the results will be published in a major medical journal by the end of 2022. Previous publication and dissemination plan: The study protocol and a description of the recruitment experience and participant baseline characteristics will be published before study completion. On completion of the trial, the database will be locked and analysed by the staff of the Robertson Centre for Biostatistics, University of Glasgow. A final study report will be prepared and the results will be published in a major medical journal in January 2021. |
| IPD sharing plan | The data sharing plans for the current study are not fully formulated and will be made available at a later date. However they will be based on the following strategy: The study database will be held at the Robertson Centre for Biostatistics University of Glasgow. After planned publications have been completed, the study Publications Committee will review applications for additional data analyses, data access, collaborative analyses (eg meta-analyses and pooling projects). In considering these requests, the Publications Committee will take into account the cost of meeting requests, the scientific validity of the requests, overlap with other requests, other legal and ethical issues, patient consent issues and information governance issues. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 17/12/2022 | 08/09/2023 | Yes | No |
Editorial Notes
08/09/2023: Publication reference and total final enrolment added.
07/09/2022: The following changes have been made:
1. The overall trial end date has been changed from 30/06/2022 to 31/08/2022 and the plain English summary has been updated accordingly.
2. The primary outcome measure has been updated.
3. The secondary outcome measures have been updated.
4. The publication and dissemination plan has been changed.
5. The intention to publish date has been updated from 01/07/2022 to 31/12/2022.
28/06/2022: The trial participating centres “Hairmyres Hospital”, “Dumfries and Galloway Royal Infirmary”, “Princess Royal Hospital”, “The Queen Elizabeth Hospital”, “Croydon Health Services NHS Trust”, and “University Hospital Ayr” have been added.
16/03/2022: The following changes have been made:
1. The overall trial end date has been changed from 31/03/2022 to 30/06/2022.
2. The interventions have been updated.
3. The primary outcome measure has been updated.
4. The secondary outcome measures have been updated.
5. The trial website has been added.
6. The plain English summary has been updated.
16/11/2021: The following changes have been made:
1. The recruitment end date has been changed from 30/11/2021 to 15/10/2021.
2. The intention to publish date has been changed from 01/04/2022 to 01/07/2022.
12/10/2021: The following changes were made to the trial record:
1. The intervention type was changed from 'other' to 'drug'.
2. The phase was added.
3. The drug name was added.
31/08/2021: The recruitment end date was changed from 30/08/2021 to 30/11/2021.
15/06/2021: The recruitment end date was changed from 30/06/2021 to 30/08/2021.
17/02/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2020 to 30/06/2021.
2. The overall trial end date was changed from 28/02/2021 to 31/03/2022.
3. The intention to publish date was changed from 30/09/2021 to 01/04/2022.
01/05/2020: Due to current public health guidance, recruitment for this study has been paused.
10/01/2020: The full addresses of all the trial participating centres have been added.
31/12/2019: The following changes were made to the trial record:
1. The secondary outcome measures were changed.
2. The exclusion criteria were changed.
3. The recruitment end date was changed from 31/12/2019 to 31/12/2020.
4. The sponsor address was updated
5. By this date the following trial participating centres were open: Queen Alexandra Hospital, Glasgow Royal Infirmary, Golden Jubilee National Hospital, Queen Elizabeth University Hospital, Salford Royal Hospital, Basingstoke and North Hampshire Hospital, Glenfield Hospital , Royal Sussex County Hospital, Royal Glamorgan, West Middlesex University Hospital, Manchester Royal Infirmary, Ninewells Hospital, Royal Alexandra Hospital, St Bartholomew’s Hospital, University College London Hospital, Castle Hill Hospital, Raigmore Hospital, Monklands Hospital, Royal Infirmary of Edinburgh, Liverpool Heart and Chest Hospital, Royal Bournemouth Hospital, Aberdeen Royal Infirmary, Royal Devon and Exeter, University Hospital Coventry, King’s College Hospital, Morriston Hospital, University Hospital Crosshouse, Wythenshawe Hospital, Royal Brompton and Harefield (Harefield Hospital), Ulster Hospital , Great Western Hospital , District General Hospital , North Middlesex University Hospital , Royal Gwent Hospital, Aintree University Hospital, University Hospital Llandough, University Hospital Southampton, Barnet Hospital , Antrim Area Hospital, Blackpool Teaching Hospitals , Bradford Royal Infirmary, Chesterfield Royal Hospital, Darlington Memorial Hospital, Forth Valley Royal Hospital, Hammersmith Hospital, New Cross Hospital, Nottingham University Hospital, Poole Hospital, Northern General Hospital, Southend University Hospital, Victoria Hospital, Wansbeck General Hospital , Wycombe General Hospital, City Hospitals Sunderland, Torbay Hospital, Royal Victoria Hospital, Guy’s and St Thomas’ Hospital, Doncaster Royal Infirmary, Royal Stoke University Hospital, St George’s Hospital, Broomfield Hospital, John Radcliffe Hospital, Salisbury District Hospital, Kingston Hospital, Royal Oldham Hospital, Basildon University Hospital, Watford General Hospital, St Richard’s Hospital, Princess of Wales Hospital, Bristol Royal Infirmary, Royal Cornwall Hospital.
28/03/2019: The condition has been changed from "Specialty: Cardiovascular disease, Primary sub-specialty: Other; UKCRC code/ Disease: Cardiovascular/ Other and unspecified disorders of the circulatory system" to "Heart failure and iron deficiency" following a request from the NIHR.
08/10/2018: The following changes have been made to the trial record:
1. The participant inclusion criterion 5.1 has been changed from "Current (with intention to discharge in next 48 hours) or recent (within 6 months) hospitalisation for HF, or" to "Current (with the expectation that patient will survive to discharge) or recent (within 6 months) hospitalisation for HF, or"
2. The participant exclusion criteria have been updated
3. The recruitment end date has been changed from 31/08/2018 to 31/12/2019
4. The intention to publish date has been changed from 31/01/2021 to 30/09/2021
01/06/2018: Internal review
31/05/2018: The following changes have been made:
1. The secondary outcome measures have been changed.
2. The participant inclusion criteria have been changed.
3. The participant exclusion criteria have been changed.
4. By this date the following trial centres were open: Queen Alexandra Hospital, Glasgow Royal Infirmary, Golden Jubilee National Hospital, Queen Elizabeth University Hospital, Salford Royal Hospital, Basingstoke and North Hampshire Hospital, Glenfield Hospital, Royal Sussex County Hospital, Royal Glamorgan Hospital, West Middlesex University Hospital, Manchester Royal Infirmary, Ninewells Hospital, Royal Alexandra Hospital, St Bartholomew’s Hospital, University College London Hospital, Castle Hill Hospital, Raigmore Hospital, Monklands Hospital, Royal Infirmary of Edinburgh, Liverpool Heart and Chest Hospital, Royal Bournemouth Hospital, Aberdeen Royal Infirmary, Royal Devon and Exeter Hospital, University Hospital Coventry, King’s College Hospital, Morriston Hospital, University Hospital Crosshouse, Wythenshawe Hospital, Royal Brompton and Harefield (Harefield Hospital), Ulster Hospital, Great Western Hospital, District General Hospital, North Middlesex University Hospital, Royal Gwent Hospital, Aintree University Hospital, University Hospital Llandough, University Hospital Southampton, Barnet Hospital, Antrim Area Hospital, Blackpool Teaching Hospitals, Bradford Royal Infirmary, Chesterfield Royal Hospital, Darlington Memorial Hospital, Forth Valley Royal Hospital, Hammersmith Hospital, New Cross Hospital, Poole Hospital, Princess Royal Hospital, Northern General Hospital, Southend University Hospital, Victoria Hospital, Wansbeck General Hospital, Wycombe General Hospital, Sunderland Royal Hospital, Torbay Hospital, Royal Victoria Hospital, Guy’s and St Thomas’ Hospital, Doncaster Royal Infirmary, Royal Stoke University Hospital, Broomfield Hospital, John Radcliffe Hospital, Kingston Hospital, Royal Oldham Hospital.
