Title: A pilot cohort study of intravenous iron for the treatment of iron deficiency in adults with cystic fibrosis
Funder: Department of Health and Social Care

Abstract: Background Cystic fibrosis (CF) is a genetic condition characterised by poor nutrient absorption from the gut and chronic lung infection. Historically, it was fatal in childhood, but life expectancy is increasing. By 2025, some 14,000 patients and their families will be living with CF in the UK, of whom over 50% will be adults. These patients may be active and in full-time work, but they are often dependent upon expensive and time-consuming treatments, experience poor health-related quality of life, and require regular contact with healthcare teams. Iron deficiency is reported in up to 60% of adults with CF, and is usually unresponsive to oral supplements. In other chronic diseases, iron deficiency is routinely treated with intravenous (IV) iron, which has been shown to be safe in these conditions, and is often very effective. In patients with heart failure and iron deficiency, for example, IV iron substantially improves quality of life and exercise capacity, and reduces hospital admissions, even in the absence of anaemia. It has been shown to be cost-effective in this setting. If similar benefits of IV iron were seen in patients with CF, for whom treatment options are currently limited, this would represent an important therapeutic advance. Nevertheless, IV iron is not routinely used in this group, due to specific concerns about encouraging the growth of iron-dependent bacteria such as Pseudomonas in the CF lung. To date, however, these concerns remain largely theoretical, because no robust clinical studies of IV iron have been performed in patients with CF. Aims and objectives Currently, it is unknown whether IV iron should be used routinely to treat iron deficiency in CF. On the one hand, it is possible that a safe, cheap and effective treatment is being avoided unnecessarily. On the other, it is possible that patients with CF who do receive IV iron, for example those with iron deficiency associated with severe anaemia, are being exposed to a significant risk of infection. We aim to address this position of clinical equipoise by assessing the early safety profile of IV iron in a group of adults with CF. Our primary objective is to assess the hypothesis that IV iron is safe in patients with CF, and that it is not associated with early microbiological deterioration. Our secondary objectives include an assessment of whether IV iron is effective at increasing iron availability in patients with CF, and the collection of preliminary data on patient-focused clinical outcomes, to confirm the feasibility of these measurements and inform sample size calculations for future studies. Research plan and patient benefit To achieve these objectives, we will undertake a pilot cohort study of IV iron administration in 20 adults with CF and iron deficiency. Participants will be studied prospectively over a period of 16 weeks, including an initial 4-week run in period of data collection prior to IV iron, followed by a 12-week period of data collection after IV iron. Each participant will undertake a total of four study visits. The primary outcome will be a comparison of the incidence of deteriorating infective status, based on a novel objective definition, during the 4-week period after IV iron, compared with the 4-week period before IV iron. We expect the findings of this pilot study to inform the design of a larger multi-centre trial of IV iron in the future, focused on patient-centred outcomes such as exercise tolerance and health-related quality of life. Any effect of iron on these outcomes would have significant implications for the wellbeing of patients with CF, and the potential to generate substantial NHS cost savings, through reduced use of healthcare resources by these patients.

Lay abstract: Cystic fibrosis (CF) is an inherited condition affecting over 10,000 patients in the UK. People with CF experience problems in the lungs and bowel. In the lungs, long-term bacterial infection leads to lung damage over many years. In the bowel, food and nutrients are poorly absorbed, leading to malnutrition. In the past, patients with CF died in childhood, but most now survive into adulthood. They often remain active and may work full-time, but they usually require expensive and time-consuming treatments, have poor health-related quality of life, and make frequent visits to hospital. There is a genuine need for safe, effective and affordable treatments to improve their wellbeing. Patients with long-term illness often have low iron levels, which usually cannot be treated with iron tablets. However, iron can be given intravenously (directly into a vein). Intravenous (IV) iron is safe and beneficial in many chronic illnesses. In patients with heart failure, for example, it leads to improved symptoms, improved exercise capacity, and less time spent in hospital. Despite these possible benefits, IV iron is rarely used in patients with CF, as there is a theoretical risk that it could encourage bacterial growth in the lungs, leading to more infection. Unfortunately, no studies of IV iron have been performed in CF patients, so the true risks and benefits are unknown. It is therefore possible that a simple, effective and inexpensive treatment, which could benefit patients with CF, is being avoided unnecessarily. To improve the care of patients with CF, we are planning a preliminary study investigating the effects of IV iron in 20 adults with CF and low iron levels. This study will provide important information on whether IV iron is safe, help us to decide whether a larger study should be done, and help in the design of any future study.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: BLOOD;CONGENITAL DISORDERS