Chronic Heart Failure, Iron Deficiency, Left Ventricular Systolic Dysfunction
Conditions
Keywords
Intravenous iron, PROBE design
Brief summary
This study will address whether the additional use of Intravenous (IV) iron on top of standard care will improve the outlook for patients with heart failure and iron deficiency. One group of participants will receive treatment with iron injections and the other group will not receive any iron injections.
Detailed description
Chronic heart failure (CHF) is a very common medical problem. Despite improvements in treatment, many patients suffer limiting symptoms of shortness of breath and fatigue. Hospitalisation for CHF is common and life expectancy reduced. Many patients with CHF have a deficiency of iron (low iron levels or cannot use iron properly), and this is associated with poorer outcomes. Some small research studies have suggested that giving patients intravenous iron improves symptoms in the short term. It is unknown, however, whether correcting iron deficiency is beneficial to patients with CHF in the long term and whether it improves life expectancy and keeps them out of hospital. This study will help us answer these key questions. This study will address whether the additional use of Intravenous (IV) iron on top of standard care will improve the outlook for patients with heart failure and iron deficiency. One group of participants will receive treatment with iron injections and the other group will not receive any iron injections. The study will take place in about 70 secondary care sites (hospitals) across the UK. Participants will be recruited over a period of about five years and will be followed up for a minimum of three months (average duration of about four years per participant). After the initial visits, participants will be seen every four months.
Interventions
Sponsors
NHS Greater Glasgow and Clyde
Pharmacosmos A/S
British Heart Foundation
University of Glasgow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥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 ug/L 5. Evidence of being in a higher risk HF group: (a) Current (with the expectation that patient will survive to discharge) or recent (within 6 months) hospitalisation for HF, OR (b) 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
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/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: (a) planned cardiac surgery or revascularisation; (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 (see Appendix 3) 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 disease. 9. Participation in another intervention study involving a drug or device within the past 90 days (co-enrolment in observational studies is permitted)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CV mortality or hospitalisation for worsening heart failure (analysis will include first and recurrent hospitalisations) | Minimum of 3 months follow-up from last patient recruited |
Secondary
| Measure | Time frame |
|---|---|
| CV hospitalisation (first event) | Minimum of 3 months follow-up from last patient recruited |
| CV death or hospitalisation for heart failure analysed as time to first event | Minimum of 3 months follow-up from last patient recruited |
| Overall Score from Minnesota Living with Heart Failure | At 4 months |
| Cardiovascular mortality | Minimum of 3 months follow-up from last patient recruited |
| Overall EQ-5D VAS | At 4 months |
| Overall EQ-5D index | At 4 months |
| CV mortality or hospitalisation for major CV event (stroke, MI, heart failure) (first event) | Minimum of 3 months follow-up from last patient recruited |
| All-cause mortality | Minimum of 3 months follow-up from last patient recruited |
| Hospitalisation for worsening heart failure (recurrent events) | Minimum of 3 months follow-up from last patient recruited |
| Combined all-cause mortality or first all-cause unplanned hospitalisation | Minimum of 3 months follow-up from last patient recruited |
| Physical domain of QoL (Minnesota Living With Heart Failure) | At 4 months |
| Overall Score from Minnesota Living With Heart Failure | At 20 months |
| Days dead or hospitalised | At 36 months |
| Quality-adjusted days alive and out of hospital | At 12 months |
| 6 minute walk test | At 4 months |
| Death due to infection | Minimum of 3 months follow-up from last patient recruited |
| Hospitalisation primarily for infection (first event) | Minimum of 3 months follow-up from last patient recruited |
| All-cause hospitalisation (first event) | Minimum of 3 months follow-up from last patient recruited |
Countries
United Kingdom
Outcome results
None listed