|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Cystic fibrosis is a genetic disease that causes an abnormality of mucus production in the lungs, leading to progressive lung damage and susceptibly to lung infection.
|Diseases [C] - Respiratory Tract Diseases [C08]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To assess the early safety profile of IV iron in adults with CF by comparing the incidence of new infective events during the 4 weeks before and after IV iron
|Secondary objectives of the trial
|1) To compare the incidence of new infective events during the 12 weeks before and after IV iron.
2) To assess the impact of IV iron on airway microbiology, including incidence and severity of exacerbations.
3) To assess the effect of IV iron on systemic iron and inflammatory status.
4) To assess the impact of IV iron on standard indices of CF disease severity.
5) To assess the impact of IV iron on health-related quality of life.
6) To assess the acceptability of the intervention and trial procedures.
7) To explore the feasibility of measuring exercise capacity and lung blood pressure in adults with cystic fibrosis.
8) To assess the effect of IV iron on sputum and systemic iron and inflammatory status during infective exacerbations of CF.
|Trial contains a sub-study
|Principal inclusion criteria
|- Age ≥18 years
- Established diagnosis of cystic fibrosis
- Iron deficiency (transferrin saturation ≤16 % or ferritin <15 μg/l, within last four months)
- Able to provide informed consent
|Principal exclusion criteria
|- Urgent (<6 weeks) need for intravenous iron
- Active infection (currently requiring IV antibiotics)
- Previous intravenous iron supplementation (within last four months)
- Current oral supplementation
- Hypersensitivity to ferric carboxymaltose
- Active non-tuberculous mycobacterial pulmonary disease (as defined by ATS-IDSA criteria)
- Liver failure
- Ferritin >300 g/l or transferrin saturation >45%
- Pregnancy or breast feeding
- Previous transplantation
- Judged by a designated member of the trial team to be unlikely to comply with safety aspects of the trial protocol.
|E.5 End points
|Primary end point(s)
|The incidence of new infective events in the four weeks before intravenous iron, compared with the four weeks after intravenous iron, where a new infective event is defined as any of:
1) New microbiological isolate on routine sputum culture (organism not cultured in 12 months prior to study);
2) Clinical infection requiring IV antibiotics (as judged by the clinical team based on routine clinical data);
3) Admission to hospital for infection-related reason (as judged by clinical team based on routine clinical data);
4) Significant deterioration in lung function (>10% fall in FEV1), not otherwise explained (as judged by clinical team, based on routine clinical data).
|Timepoint(s) of evaluation of this end point
|One month after administration of IMP.
|Secondary end point(s)
|Incidence of new infective events during the 12-week period before intravenous iron, compared with the 12-week period after intravenous iron.
Change in number of IV and oral antibiotic days.
Sputum iron levels, sputum culture and cell counts, respiratory microbiota analysis.
Change in blood and sputum markers of iron and inflammation.
Change in arterial oxygen saturation, body mass index and lung function (forced expiratory volume in 1 second, forced vital capacity).
Change in CFQ-R and SF-36 questionnaire scores.
Change in exercise capacity (shuttle walk test) and echocardiographic assessment of systolic pulmonary artery pressure.
Percentage of eligible patients entering and completing the study.
|Timepoint(s) of evaluation of this end point
|Weeks 0, 4, 8 and 16 (the intervention is given at week 4)
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|Outcomes designed to provide preliminary data for future trial design.
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
|Other trial design description
|The design is of an interventional cohort study, with each patient acting as their own control.
| Comparator of controlled trial
|Other medicinal product(s)
|For each patient, a comparison will be made of outcomes before and after the intervention
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The end of the trial for each patient is the end of the final follow-up visit (visit 4, week 12). The end of the whole trial is one year after the end of the final follow-up visit for the final participant (to allow for sample analysis after the end of patient participation).
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days